Durvalumab - Celgene/MedImmune

At a glance

Originator MedImmune
Developer AIO Studien gGmbH; AstraZeneca; AVEO Oncology; Big Ten Cancer Research Consortium; Biocompatibles International; Canadian Cancer Trials Group; Cancer Research UK; Case Comprehensive Cancer Center; Celgene Corporation; Celgene International SARL; Centre hospitalier de l'Universite de Montreal; Centre Leon Berard; Charite - Universitatsmedizin Berlin; Childrens Hospital Los Angeles; Daiichi Sankyo Company; Dana-Farber Cancer Institute; Eli Lilly and Company; European Network of Gynaecological Oncological Trial Groups; Fondazione IRCCS Istituto Nazionale dei Tumori; Gradalis; Grand Hopital de Charleroi; Grupo Espanol de Tumores Neuroendocrinos; GSK; Gustave Roussy; Immunocore; Innate Pharma; Institut Claudius Regaud; Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori; Jules Bordet Institute; Juno Therapeutics; Kyoto Breast Cancer Research Network; Ludwig Institute for Cancer Research; M. D. Anderson Cancer Center; MedImmune; Memorial Sloan-Kettering Cancer Center; Mirati Therapeutics; Myriad Genetic Laboratories; National Cancer Institute (USA); National Health and Medical Research Council; NHS Greater Glasgow and Clyde; Nordic Society of Gynaecological - Clinical Trial Unit; Northwestern University; Pharmacyclics; Radboud University; Samsung Medical Center; Spanish Oncology Genito-Urinary Group; Swiss Group for Clinical Cancer Research; SWOG; UNC Lineberger Comprehensive Cancer Center; Undisclosed; UNICANCER; University College London; University Health Network; University of Colorado at Denver; University of Kansas Medical Center; University of Maryland Greenbaum Cancer Center; University of Southern California; University of Sydney; University of Texas M. D. Anderson Cancer Center; VentiRx Pharmaceuticals; Washington University School of Medicine; Yale University; Yonsei University College of Medicine
Class Antineoplastics; Immunotherapies; Monoclonal antibodies
Mechanism of Action Programmed cell death-1 ligand-1 inhibitors; T lymphocyte stimulants

Orphan Drug Status

Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

Yes - Biliary cancer; Small cell lung cancer; Liver cancer
New Molecular Entity Yes

Highest Development Phases

Marketed Non-small cell lung cancer; Small cell lung cancer
Registered Biliary cancer; Liver cancer; Urogenital cancer
Phase III Bladder cancer; Cervical cancer; Endometrial cancer; Fallopian tube cancer; Gastric cancer; Head and neck cancer; Malignant-mesothelioma; Oesophageal cancer; Ovarian cancer; Peritoneal cancer; Renal cell carcinoma; Solid tumours; Triple negative breast cancer
Phase II/III Pancreatic cancer
Phase II Acute myeloid leukaemia; Brain metastases; Breast cancer; Cholangiocarcinoma; Colorectal cancer; Diffuse large B cell lymphoma; Gallbladder cancer; Germ cell cancer; Glioblastoma; HER2 negative breast cancer; Malignant melanoma; Multiple myeloma; Myelodysplastic syndromes; Neuroendocrine tumours; Non-Hodgkin's lymphoma; Oropharyngeal cancer; Prostate cancer; Sarcoma; Soft tissue sarcoma; Squamous cell cancer; Uterine cancer
Phase I/II Chronic lymphocytic leukaemia; Cutaneous T-cell lymphoma; Haematological malignancies; Lung cancer; Lymphoma; Peripheral T-cell lymphoma; Renal cancer
No development reported CNS cancer; Gastrointestinal cancer; Lymphoproliferative disorders; Thyroid cancer; Vulvovaginal cancer

Most Recent Events

16 Apr 2024 Updated efficacy data from the phase III TOPAZ-1 trial in cholangiocarcinoma released by AstraZeneca
01 Mar 2024 AstraZeneca suspends phase II SOUND trial in Non-small cell lung cancer (Combination therapy, In adults, In children, In adolescents, In the elderly, Late-stage disease, Metastatic disease, Second-line therapy or greater) in China (IV) to evaluate risks and benefits of the study (NCT05374603)
22 Feb 2024 Phase-II clinical trials in Non-small cell lung cancer (In adults, In the elderly, Neoadjuvant therapy, First-line therapy) in USA, Sweden, Spain, Portugal, Italy, Hungary, Germany, France, Czech Republic, Canada, Austria (IV) ( NCT05925530)

Development Overview

Introduction

Durvalumab (MEDI 4736) is a fully human monoclonal antibody directed against programmed death ligand-1 (PD-L1), developed by MedImmune (a subsidiary of AstraZeneca) and Celgene, for the treatment of various cancers. Durvalumab is an immunoglobulin G1 kappa (IgG1κ) antibody that blocks the interaction of PD-L1 (CD274 or B7 homolog 1) with PD-1 and CD80 (B7.1) on T cells thus reducing self-tolerance and immunosuppression, which allows the immune cells to find and destroy the cancerous tissue. Durvalumab is launched for non-small cell lung cancer (NSCLC) in the US, Netherlands, the UK and Japan and approved in Canada, India, Switzerland, EU, Brazil, China. Durvalumab is launched for small cell lung cancer (SCLC) Netherlands. The drug is available in the US and approved in the EU, Japan, Singapore and China, for small cell lung cancer. The product is under regulatory review for NSCLC in South Korea. It is approved in Canada, Brazil, India, Israel, UAE, Australia, Hong Kong, Qatar, Macau for urogenital cancer. The drug product is withdrawn for urogenital cancer in the US. The candidate is approved in EU, Liechtenstein, Iceland, Norway and Japan for biliary tract cancer. The candidate is approved in Japan, US, EU for hepatocellular cancer. Drug is under regulatory review for Biliary cancer in Australia, Brazil, Canada, Israel, Singapore, Switzerland, the United Kingdom. Drug is under regulatory review for Small cell lung cancer in China. Clinical development is underway in several countries worldwide.

AstraZeneca discontinued the development of durvalumab for pancreatic cancer, in the US, and suspended evaluations in multiple myeloma in the US, Canada, Denmark, Finland, Germany, Italy, the Netherlands and Spain. Phase I development in solid tumours was conducted in Canada, South Korea, the US, Israel, Taiwan, Germany, the UK, the Netherlands, Spain. Phase Ib development in breast cancer was conducted in Canada, Taiwan, South Korea. Phase I development in non-Hodgkin's lymphoma was conducted in the US. Phase I development in pancreatic cancer was conducted in France, Spain, South Korea, the US. Phase I development in diffuse large B cell lymphoma was conducted in France, Italy, Ireland and the UK. Phase I development in multiple myeloma was conducted in the US, France, Netherlands, Canada, Germany, Italy and Spain. Phase I development in CNS cancer was conducted in the US. Phase I development in lymphoma was conducted in the US. Phase I development in myelodysplastic syndromes was conducted in the US, France, Germany, the UK. Clinical development in renal cell carcinoma was conducted in the US, France and Spain. Phase I development in thyroid cancer was conducted in the US. However, no recent reports of development were identified.

Durvalumab has emerged from MedImmune's research programme of anticancer monoclonal antibodies [see AdisInsight drug profile 800034274].

MedImmune, in collaboration with Ventana Medical Systems, is developing a personalised PD-L1 immuno-histochemistry assay [see AdisInsight drug profile 800040741] to screen patients that enrol in clinical trials of durvalumab. This includes the ATLANTIC trial for NSCLC that will enrol only patients that express PD-L1 as determined by the VENTANA assay. The companion diagnostic is approved in the US for the assessment of the PD-L1 protein in formalin-fixed, paraffin-embedded urothelial carcinoma tissue.

In July 2019, Kyowa Hakko Kirin changed its name to Kyowa Kirin^[1]. In March 2020, NewLink Genetics Corporation and Lumos Pharma merged to form Lumos Pharma^[2].

As at August 2020, no recent reports of development had been identified for phase-I development in Lymphoproliferative disorders in USA (IV), phase-I development in Oropharyngeal-cancer (Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA (IV), phase-I development in Oropharyngeal-cancer (Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater) in USA (IV).

As at August 2022, no recent reports of development had been identified for phase-I development in Cervical-cancer in Netherlands (IV, Infusion), phase-I development in Head-and-neck-cancer (Combination therapy, Adjuvant therapy) in USA (IV, Infusion), phase-I development in Head-and-neck-cancer (Combination therapy, First-line therapy, Metastatic disease, Recurrent, Second-line therapy or greater) in Canada (IV, Infusion), USA (IV, Infusion), phase-I development in Solid-tumours (Combination therapy, In the elderly, Late-stage disease, In adults) in USA (IV, Infusion), Australia (IV, Infusion), South Korea (IV, Infusion), phase-I development in Bladder-cancer (Combination therapy, In the elderly, Neoadjuvant therapy, In adults) in USA (IV), phase-I development in Ovarian-cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater) in France (IV, Infusion), phase-I development in Soft tissue sarcoma (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater) in France (IV, Infusion), phase-I development in Cholangiocarcinoma (Combination therapy, Late-stage disease) in USA (IV, Infusion), phase-I development in Liver-cancer (Combination therapy, Late-stage disease) in USA (IV, Infusion), phase-I development in Pancreatic-cancer (Combination therapy, Late-stage disease) in USA (IV, Infusion), phase-I development in Solid-tumours (Combination therapy, Late-stage disease) in Japan (IV, Infusion), Taiwan (IV, Infusion), phase-I development in Vulvovaginal-cancer (Combination therapy, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater) in USA (IV, Infusion), phase-I development in Liver-cancer (Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA (IV, Infusion), France (IV, Infusion), phase-I development in Gastrointestinal-cancer (Combination therapy, Late-stage disease, Second-line therapy or greater) in USA (IV, Infusion), phase-I development in Solid-tumours (Combination therapy, Late-stage disease, Second-line therapy or greater) in Australia (IV, Infusion), phase-I development in Breast-cancer (Combination therapy, Second-line therapy or greater) in USA (IV, Infusion), phase-I development in Solid-tumours (In the elderly, Late-stage disease, In adults) in South Korea (IV, Infusion), Taiwan (IV, Infusion), Japan (IV, Infusion), phase-I development in Bladder-cancer (In the elderly, Monotherapy, Neoadjuvant therapy, In adults) in USA (IV), phase-I development in Breast-cancer (Monotherapy, Second-line therapy or greater) in USA (IV, Infusion), phase-I development in Diffuse large B cell lymphoma (Second-line therapy or greater) in Australia (IV, Infusion).

In March 2023, Sesen Bio merged with Carisma Therapeutics to form Carisma Therapeutics^[3].

In January 2023, AVEO Oncology was acquired by LG Chem^[4].

In January 2024, Mirati Therapeutics was acquired by Bristol-Myers Squibb^[5].

Company Agreements

In June 2017, Sesen Bio (now Carisma Therapeutics) signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) on the development of Eleven's oportuzumab monatox (Vicinium^TM) in combination with AstraZeneca's durvalumab (Imfinzi^TM; [see Adis Insight Drug profile 800037095]), for the treatment of non-muscle invasive bladder cancer. Under the terms of CRADA, NCI Center for Cancer Research, Urologic Oncology Branch, will conduct a phase I clinical trial in patients with high-grade NMIBC to evaluate the safety, efficacy, and biological correlates of the vicinium and durvalumab combination therapeutic strategy^[6]^[7]^[3]

In January 2023, AIM ImmunoTech entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca. Under the agreement, Erasmus MC is planning to perform an investigator-initiated DURIPANC Study, entitled “Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect. Both study drugs will be provided by AstraZeneca and AIM ImmunoTech.^[8]

In January 2018, Innate Pharma entered into a non-exclusive clinical trial collaboration with Medimmune (now AstraZeneca) to conduct the phase I/II STELLAR-001 trial. Innate Pharma will conduct the trial to assess the safety and efficacy of durvalumab plus IPH 5401 for the treatment of patients with selected solid tumours. Both the companies will equally share the expenses of the trial^[9]^[10]

In July 2018, MedPacto and AstraZeneca entered into a clinical collaboration to evaluate the safety and efficacy of MedPacto’s vactosertib (TEW-7197) in combination with durvalumab in patients with metastatic non-small cell lung cancer. Under the terms of the agreement, MedPacto and AstraZeneca will collaborate on a non-exclusive basis to evaluate the combination of the two drugs in NSCLC. MedPacto will sponsor and fund the study and AstraZeneca will supply durvalumab for the study.^[11]

Immunomedics and AstraZeneca entered into a collaboration in July 2018, to conduct a phase I/II trial for sacituzumab govitecan in combination with durvalumab in patients with triple negative breast cancer and urothelial cancer.^[12]

In February 2018, Syndax Pharmaceuticals entered into a non-exclusive clinical trial collaboration with AstraZeneca, to evaluate the safety and efficacy of the former's SNDX 6352 (also known as UCB 6352), in combination with the latter's durvalumab, for the treatment of solid tumours. Under the terms of the agreement, in the first half of 2018, Syndax will initiate a phase Ib trial to establish the safety and recommended dose regimen of the combination therapy. Both the companies can use the data from the phase Ib trial to sponsor, design and initiate subsequent phase II studies, aimed at assessing the safety and efficacy of the combination therapy in different types of solid tumours.^[13]

In September 2017, NewLink Genetics Corporation signed a clinical collaboration agreement with AstraZeneca to evaluate the combination of indoximod and durvalumab along with standard of care chemotherapy for patients with metastatic pancreatic cancer.^[14]

In July 2017, Merck entered into a global strategic oncology collaboration with AstraZeneca to co-develop and co-commercialise AstraZeneca’s olaparib (Lynparza) and selumetinib as monotherapy and in combination treatments for multiple cancer types. Merck and AstraZeneca will independently develop and commercialise olaparib and selumetinib in combinations with the companies’ respective PD-1 and PD-L1 immuno-oncology medicines pembrolizumab and durvalumab. Merck will fund all development and commercialization costs of pembrolizumab in combination with olaparib or selumetinib. AstraZeneca will fund all development and commercialization costs of durvalumab in combination with olaparib or selumetinib. AstraZeneca will receive up to $US8.5 billion in total consideration, including $US1.6 billion upfront, $US750 million for certain license options and up to an additional $US6.15 billion upon successful achievement of future regulatory and sales milestones. Under their agreement, gross profits from selumetinib product sales generated through monotherapy or combination therapies will be shared equally. AstraZeneca will book all product sales of selumetinib and gross profits due to Merck under the collaboration will be recorded by AstraZeneca under cost of sales. Earlier in June 2009, AstraZeneca and Merck entered a collaboration agreement to investigate the therapeutic potential of combining two investigational compounds, selumetinib and MK 2206, as a new anticancer regimen. Under the terms of the agreement, AstraZeneca and Merck would collaborate to evaluate the co-administration of MK 2206 and selumetinib in a phase I trial in patients with solid tumours; all development costs will be shared. Opportunities for further clinical development would be assessed by the two companies on completion of the phase I trial.^[15]^[16]^[17]^[18]

In August 2015, MedImmune and Mirati Therapeutics entered into an exclusive clinical trial collaboration to evaluate the safety and efficacy of MedImmune’s, durvalumab, in combination with Mirati’s, mocetinostat, in patients with non-small cell lung cancer (NSCLC) during a phase I/II trial [see Adis Insight drug profile 800020983]. Under the agreement, Mirati will conduct and fund the initial phase I/II trial, which will be overseen by a Joint Steering Committee. MedImmune will have an exclusive period of time to negotiate a commercial license for the of the combination therapy in NSCLC indication following the positive results from the initial clinical trial^[19].

In August 2015, AstraZeneca entered into a non-exclusive clinical trial collaboration with Peregrine (now Avid Bioservices) to conduct a phase I/Ib trial of the former's durvalumab latter's in combination with bavituximab [see AdisInsight drug profile 800022616] in multiple solid tumours. Pursuant to the terms of the agreement, Peregrine will conduct the initial phase I part of the trial^[20].

In October 2015, Peregrine Pharmaceuticals announced that it has expanded its clinical collaboration with AstraZeneca to include a global phase II trial of durvalumab in combination with bavituximab in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). Patients will be evaluated retrospectively for the correlation between their PD-L1 levels and clinical outcomes. The randomised trial will be conducted by Peregrine^[21]^[22].

In May 2015, AstraZeneca entered into a clinical trial collaboration with Eli Lilly to investigate the safety and preliminary efficacy of the combination therapy of durvalumab with the latter’s vascular endothelial growth factor receptor 2 antagonist, ramucirumab [see AdisInsight drug profile 800021478]. As per the agreement, Eli Lilly will sponsor the phase I study of the combination therapy for the treatment of patients with advanced solid tumours. Further details of the agreement, including tumours to be studied and financial terms, were undisclosed^[23]. The companies' collaboration was expanded in October 2015, to also explore the combination of durvalumab with galunisertib, LY 2510924, or IMC CS4 in patients with solid tumours [see AdisInsight drug profiles 800028406, 800034546 and 800034411]^[24]. Under the expanded agreement, Lilly and AstraZeneca will evaluate the safety and efficacy of the said combinations, with Lilly leading the execution of the studies. Both companies will contribute resources. As with the initial agreement, other details of the expanded agreement were not disclosed^[25].

In April 2015, MedImmune and Celgene International II Sarl entered into an exclusive collaboration to develop and commercialise durvalumab as a monotherapy and in combination with other anticancer drugs for haematologic malignancies including non-Hodgkin’s lymphoma, myelodysplastic syndromes and multiple myeloma. Under the agreement, Celgene will make an upfront payment of US$450 million, lead clinical development across all clinical trials and be responsible for all research and development costs until the end of 2016, following which Celgene will undertake 75% of these costs. MedImmune will continue to manufacture and book all sales of the drug and will pay royalty to Celgene on worldwide commercialisation of approved durvalumab indications in haematology. The royalty rates will begin with 70% and will decrease to 50% of the global sales of durvalumab in haematological indications over a period of four years. The collaboration agreement is expected to become effective in the second quarter of 2015, following the expiration or termination of applicable waiting periods under all applicable antitrust laws^[26]. Initially, the collaboration will focus on the development of combination therapy of durvalumab with Celgene’s pipeline products and other drugs for haematological disorders. The collaboration will also explore combination therapies with AstraZeneca’s anticancer drugs and could expand to include other assets^[27].

During first quarter of 2015, AstraZeneca and Gilead entered into a clinical trial collaboration to investigate durvalumab in combination with idelalisib [see AdisInsight drug profile 800025920] for the treatment of haematological cancers/solid tumours including diffuse large B-cell lymphoma, and triple negative breast cancer^[28].

AstraZeneca and Innate Pharma signed an agreement in April 2015, for the co-development of durvalumab in combination with IPH 2201 for the treatment of cancer^[29]^[30]^[31].

In November 2014, AstraZeneca and Pharmacyclics (a subsidiary of AbbVie) entered into a clinical trial collaboration to investigate combination therapies for solid tumours. The collaboration will investigate the safety and efficacy of durvalumab in combination with ibrutinib [see AdisInsight drug profile 800022023]. Preclinical data suggested that combining these compounds may result in enhanced effects compared with the treatment alone. Both Pharmacyclics and AstraZeneca will collaborate on a non-exclusive basis and may consider and conduct multiple studies. The studies will be led by Pharmacyclics. Data from these studies will determine the feasibility of further clinical development of different combinations. Financial terms of the agreement were not disclosed^[32].

In May 2015, Pharmacyclics was acquired by AbbVie^[33].

In April 2015, MedImmune and Immunocore entered into a collaboration agreement. Under the terms of which, Immunocore will conduct a phase Ib/II study of IMC gp100 [see AdisInsight drug profile 800033036] in combination with durvalumab and/or tremelimumab [see AdisInsight drug profile 800020650], for the potential treatment of metastatic melanoma. MedImmune will have the first right of negotiation for the future development of these combinations for tumours expressing gp100. Immunocore and MedImmune will collaborate to establish a dosing regimen for IMC gp100 combined with durvalumab and/or tremelimumab within the phase Ib study while the phase II study will assess the safety and efficacy of the different combinations^[34]^[35].

Also in November 2014, AstraZeneca, Pharmacyclics and Janssen Research & Development entered into a clinical trial collaboration to investigate durvalumab in combination with ibrutinib for the treatment of haematological malignancies, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma [see AdisInsight drug profile 800022023]. Preclinical data suggested that combining these compounds may result in enhanced effects compared with the treatment alone. Under the terms of the agreement, the studies will be led by Pharmacyclics. Phase I stage of the study will establish the recommended and tolerable dose and dosing schedule for the combination and the phase II stage will evaluate the safety and efficacy of the combination. Financial terms of the agreement were not disclosed^[36].

In July 2014, Advaxis and MedImmune, the development and research arm of AstraZeneca, entered into a collaboration for an immuno-oncology combination trial. Under the terms of the collaboration, both companies will team up on a phase I/II trial to evaluate the safety and efficacy of durvalumab in combination with Advaxis' axalimogene filolisbac for the treatment of advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated squamous cell carcinoma of the head and neck cancer. Advaxis will fund the study. MedImmune has a non-exclusive relationship for HPV-associated tumour types and has the first right to negotiate future development of combinations comprising axalimogene filolisbac and durvalumab^[37]. [see AdisInsight drug profile 800025081].

AstraZeneca entered into a collaboration agreement with Kyowa Hakko Kirin (now Kyowa Kirin) in August 2014 to co-fund a clinical study of durvalumab in combination with Kyowa Hakko Kirin's anti CCR4 antibody, mogamulizumab [see AdisInsight drug profile 800025071]^[38].

In January 2018, Peregrine Pharmaceuticals changed its name to Avid Bioservices^[39].

Key Development Milestones

In November 2020, the US FDA approved a new four-week, fixed-dose regimen for treatment in the approved indications of non-small cell lung cancer (NSCLC) and bladder cancer. Durvalumab will be administered intravenously every four weeks at a fixed dose of 1500mg in unresectable Stage III NSCLC after chemoradiation therapy and previously treated advanced bladder cancer, consistent with the approved dosing in extensive-stage small cell lung cancer (ES-SCLC). In August 2020, AstraZeneca's durvalumab received acceptance for its supplemental Biologics License Application (sBLA) and also granted Priority Review in the US. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision will be during the fourth quarter of 2020. The sBLA was based on data from several clinical trials, including results from the phase III CASPIAN trial in ES-SCLC which used the four-week, fixed-dose regimen during maintenance^[40]^[41].

In December 2020, AstraZeneca reported that its durvalumab has been recommended for marketing authorisation by the CHMP in the European Union (EU) for an additional dosing option of 1500 mg fixed dose every four weeks, in the approved indication of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on at least 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy (CRT). The new dosing option is consistent with the approved durvalumab dosing in extensive-stage small cell lung cancer (ES-SCLC). Following review of the application under its accelerated assessment procedure, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on data from several durvalumab clinical trials, including the PACIFIC phase III trial which supported the two-week, weight-based dosing of 10mg/kg every two weeks already approved in locally advanced, unresectable NSCLC, and the CASPIAN phase III trial which used fixed dosing every four weeks during maintenance treatment in ES-SCLC^[42].

In February 2024, AstraZeneca initiated a phase II MDT-BRIDGE trial to access study of neoadjuvant durvalumab and platinum-based chemotherapy (CT), followed by either surgery and adjuvant durvalumab or chemoradiotherapy (CRT) and consolidation durvalumab, in participants with resectable or borderline resectable stage IIb-IIIb non-small cell lung cancer (NSCLC) (NCT05925530; D9106C00002). The multicentre, open-label, single-arm, global study intends to enroll approximately 140 participants in Austria, Canada, Czech Republic, France, Germany, Hungary, Italy, Portugal, Spain, Sweden, USA^[43].

In Janaury 2023, UNICANCER in collaboration with AstraZeneca initiated a phase II DURVALUNG trial of durvalumab maintenance in frail limited disease small cell lung cancer patients after thoracic chemoradiotherapy (CRT) (NCT05617963; UC-IMM-2106). The open-label, randomised trial intends to enrol approximately 550 patients in France^[44].

In December 2021, Nordic Society of Gynaecological Oncology European Network of Gynaecological Oncological Trial Groups (ENGOT), North Eastern German Society of Gynaecological Oncology, Belgian Gynaecological Oncology Group, Hellenic Cooperative Oncology Group and Arbeitsgemeinschaft Gynaekologische Onkologie Austria initiated and enrolled first patient in the phase II DOVACC (Durvalumab Olaparib VACCine) study designed to investigate the efficacy of UV1-olaparib-durvalumab combination as maintenance therapy after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer. The primary outcome measure for DOVACC is progression-free survival for the UV1-durvalumab-olaparib triple combination versus olaparib alone (NCT04742075; ENGOT-OV56/NSGO-CTU-DOVACC). The prospective, multicenter, open-label, randomized trial intends to enroll approximately 184 participants in Denmark and may extends to across Europe from a network of more than 40 hospitals in around 10 European countries coordinated through NSGO-CTU and ENGOT. The company announced that, topline data from the trial is expected in 2023^[45]^[46].

As of September 2017, the US FDA placed partial clinical hold on five trials and full clinical hold on one trial of FUSION programme, based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[47]. Celgene has not discerned, at this time, an imbalance in the risk benefit profile in the Fusion programme; however, the clinical holds allow for additional information to be collected to further understand the risk benefit profile of the programme^[48]. In December 2015, Celgene initiated the FUSION clinical programme which includes four trials for durvalumab, in collaboration with AstraZeneca. The FUSION programme consists of six clinical trials for newly diagnosed multiple myeloma, chronic lymphocytic leukaemia, relapsed/refractory multiple myeloma, non-Hodgkin's lymphoma, myelodysplastic syndromes and acute myeloid leukaemia. In July 2016, Celgene reported that it has initiated enrolment in these trials^[49]^[50].

In August 2023, AstraZeneca initiated the phase IIIb TOURMALINE trial to assess the safety and efficacy of durvalumab IV infusion, in combination with gemcitabine-based chemotherapy regimens, in participants with advanced biliary tract cancer (aBTC) (NCT05771480; D4191C00140; EudraCT2022-002527-35). The single-arm, open-label trial intends to enrol approximately 160 patients in South Korea, and may expand the trial to the US, France, Germany, Italy, Japan, Singapore, and Spain^[51].

In April 2020, Medimmune (a wholly owned subsidiary of AstraZeneca) suspended patient enrollment in the trial due to COVID-19 pandemic. In March 2020, Medimmune initiated the phase I trial to assess the safety and tolerability and to determine the dose of IPH 5201 [see AdisInsight drug profile 800044337] that can be used as monotherapy or in combination with durvalumab +/- oleclumab in subjects with advanced solid tumors and the first patient was dosed(NCT04261075; D6770C00001). The non-randomised study was intended to enrol 204 patients in the US and may expand to France and Switzerland^[52]^[53].

In March 2022, Greg Durm in collaboration with AstraZeneca terminated a phase II trial due to low accrual (NCT03871153; HCRN LUN17-321). The open-label trial initiated in August 2019 to evaluated the concurrent chemoradiation plus durvalumab followed by surgery followed by adjuvant durvalumab in medically operable patients with surgically resectable stage III (N2) non-small cell lung cancer and enrolled 7 participants in the US^[54].

In June 2021, AstraZenaca initiated the phase I/IIa SCope-D1 trial to investigate the safety, pharmacokinetics and preliminary efficacy of subcutaneous durvalumab in patients with non-small cell lung cancer and small cell lung cancer (NCT04870112; D9072C00001; EudraCT2020-006041-18). The open-label trial intends to enrol approximately 124 patients in the US and may expand to New Zealand, Spain, Taiwan^[55].

In December 2022, Medimmune completed a phase I trial which evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of MEDI 5395 in combination with durvalumab [see AdisInsight drug profile 800037095] in patients with selected advanced solid tumours (NCT03889275; D6450C00001). This open-label trial was initiated in October 2019, enroled approximately 39 patients in the US, the UK^[56].

In May 2019, Medimmune initiated a phase I trial of intratumorally administered MEDI 1191 [see AdisInsight drug profile 800054857] in combination with intravenous durvalumab in patients with advanced solid tumours (D8510C00001; NCT03946800). The open-label, dose-escalation and expansion trial intends to enroll approximately 61 patients in the US and Spain^[57]. In August 2019, first patient was dosed in the trial^[58]. In March 2021, the company presented preliminary data from the trial at the ESMO Targeted Anticancer Therapies Virtual Congress (ESMO TAT-2021) ^[59]. In April 2023, efficacy, adverse events and pharmacodynamics data from a phase I trial in solid tumours presented at the 114th Annual Meeting of the American Association for Cancer Research (AACR-2023) ^[60].

In March 2019, AstraZeneca initiated a phase I/II study to evaluate the safety, tolerability and preliminary efficacy of durvalumab as monotherapy and in combination with tremelimumab [see AdisInsight drug profile800020650] in pediatric patients with advanced solid tumours (excluding primary malignant tumours of central nervous system) and haematological malignancies (including lymphoma and acute leukaemia), who have progressed or are refractory to standard therapies (NCT03837899; EudraCT2018-003118-42; D419EC00001). The primary purpose of the study is to determine the recommended phase II dose of durvalumab and tremelimumab. The phase II part of the study will assess the efficacy of this dose. The open-label study intends to enrol approximately 158 pediatric patients (upto 17 years) in the US, France, Italy, Netherlands, the UK and may expand to Germany^[61].

Urogenital cancer

In June 2019, AstraZeneca announced that durvalumab is also approved in Qatar and Macau for previously-treated patients with advanced urothelial cancer. Earlier in November 2018, AstraZeneca had announced that durvalumab is approved in Israel, India, United Arab Emirates, Australia, Canada, Brazil and Hong Kong for previously-treated patients with advanced urothelial cancer^[62]^[63].

In August 2023, AstraZeneca initiated recruitment in a phase III PATAPSCO trial to evaluate the safety, tolerability and efficacy of durvalumab plus BCG (induction and maintenance) combination therapy in adult participants with a histologically confirmed diagnosis of high-risk non-muscle-invasive bladder cancer (NMIBC), who have received no prior systemic therapy for NMIBC, and who are BCG-naïve (D419JC00002; NCT05943106). The open-label, single-arm, multi-center study intends to enrol approximately 100 participants in the US^[64].

In April 2022, AstraZeneca initiated the phase III ROSY-D trial to continue to provide study treatment for patients with non-small cell lung cancer and urothelial carcinoma who have participated in a parent study with durvalumab and who continue to derive clinical benefit from treatment at the end of such studies, as judged by the investigator (EudraCT2021-003031-29; NCT05303532; D4191C00137). The multicentre, open, prospective, sequential trial intends to enrol around 61 patients in Germany, Italy, South Korea, and the UK, and may expand to France, Canada^[65].

In August 2021, AstraZeneca initiated the VOLGA phase III trial to determine the efficacy and safety of durvalumab in combination with tremelimumab [see Adis profile 800020650] and enfortumab vedotin or durvalumab in combination with enfortumab vedotin for perioperative treatment in patients ineligible for cisplatin undergoing radical cystectomy for muscle invasive bladder cancer (NCT04960709; D910PC00001). The randomised, open-label trial intends to enrol 830 participants in USA and may expand to Argentina, Austria, Brazil, Canada, Chile, France, Japan, Mexico, Netherlands, Poland, South Korea, Spain^[66].

In November 2018, AstraZeneca initiated the NIAGARA phase III trial to valuate the efficacy and safety of durvalumab in combination with gemcitabine and cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in patients with muscle-invasive bladder cancer (EudraCT2018-001811-59; D933RC00001; NCT03732677). The open-label, randomised study intends to enrol approximately 1050 patients. Primary endpoints are pathologic complete response (pCR) rates at time of cystectomy following neoadjuvant treatment and event free survival (EFS). Enrolment is on-going at South Korea, Vietnam, Turkey, Taiwan, Russia, Poland, Philippines, Netherlands, Israel, Israel, Japan, France, Czech Republic, Chile, Canada, Canada, Brazil, Australia, Australia, the US and is planned at the UK, and Germany^[67]^[68].

AstraZeneca, in September 2018 initiated a phase III NILE study to to determine the efficacy and safety of durvalumab in combination with standard of care (SoC) chemotherapy followed by durvalumab in combination with tremelimumab and standard of care chemotherapy versus standard of care chemotherapy alone in patients with unresectable locally advanced or metastatic urothelial cancer (D933SC00001; NCT03682068; EudraCT 2018-001883-48; JapicCTI184160). The primary end point of the trial is to determine progression free survival (PFS) in a time frame of approximately four years. The randomized, open-label trial intends to enrol approximately 885 patients in Australia, Hungary and Russia^[69].

In May 2018, AstraZeneca initiated the POTOMAC phase III trial to evaluate the efficacy and safety of durvalumab plus BCG combination therapy, in the patients with non-muscle-invasive bladder cancer (D419JC00001; JapicCTI183968; NCT03528694). The open label trial intends to enrol approximately 975 patients in Russia, Australia, Japan, Netherlands, Spain, and the UK^[70]. Prior to November 2020, patient enrollments were completed in the trial^[71].

In March 2021, AstraZeneca in collaboration with Alliance Foundation Trials initiated a phase II trial to evaluate the efficacy of combined neoadjuvant platinum doublet chemotherapy plus durvalumab followed by surgery, postoperative radiation and adjuvant durvalumab for 13 cycles for patients with potentially resectable stage IIIA and IIIB (T1-3, N2) NSCLC(NCT04062708). The open label trial intends to enrol approximately 55 patients in the US^[72].

In January 2021, AstraZeneca in collaboration with Ottawa Hospital Research Institute, Cross Cancer Institute, Hamilton Health Sciences, Ontario Institute for Cancer Research, and Ozmosis Research initiated a phase II RADIANT trial to assess the effect of sequential radiation and durvalumab immunotherapy given as neoadjuvant treatment prior to surgery with radical cystectomy for bladder cancer (NCT04543110; OTT-19-07/OZM-105). The multicentre, open, prospective, sequential trial intends to enrol 25 adult patients in Canada^[73].

In June 2020, University Hospital Inselspital and AstraZeneca terminated the NITIMIB phase II trial due to low accrual that evaluated the safety and antitumour activity of durvalumab in combination with tremelimumab, in patients with muscle-invasive bladder cancer ineligible for cisplatin-based chemotherapy (NCT03234153). Evaluation of the objective response rate is the defined primary endpoint of the trial. The open label trial initiated in July 2018, enrolled 6 patients in Switzerland^[74].

In October 2020, Incyte withdrew a phase II trial of durvalumab and epacadostat [see AdisInsight drug profile 800025057] in patients with unresectable, recurrent, and metastatic epstein-barr virus positive nasopharyngeal cancer (NCT04231864; NCI-2019-067360; 18209) The open-label trial intended to enroll patients in the US^[75].

In February 2018, AstraZeneca reported that the Brazil Health Regulatory Agency approved durvalumab (IMFINZI^®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC), who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery. The approval was granted within ten months of submission^[76].

In February 2021, AstraZeneca withdrew the use of durvalumab (IMFINZI^®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC), in consultation with the US FDA^[77]. In May 2017, the US FDA had granted accelerated approval to durvalumab (IMFINZI^®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC), who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery^[78]. In December 2016, the US FDA granted priority review status to the Biologics License Application (BLA) for durvalumab. The PDUFA date was set for the second quarter of 2017. The BLA was filed based on the bladder cancer cohort of study 1108 [see above]^[79].

In May 2017, AstraZeneca reported that durvalumab (IMFINZI^®) will be immediately available at Biologics, a McKesson Specialty Health oncology pharmacy services company, which has been selected by AstraZeneca to be a speciality pharmacy provider in the limited distribution network for durvalumab^[80].

In November 2017, Health Canada issued a notice of compliance with conditions and granted an accelerated approval to durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma (bladder cancer) who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before or after surgery. The approval was based on results of study 1108 [see below]^[81].
In February 2016, the US FDA granted breakthrough therapy designation to durvalumab for the treatment of patients with PD-L1 positive inoperable or metastatic urothelial cancer of the bladder, whose tumour has progressed during or after one standard platinum-based regimen. The special designation was granted, based on the clinical data from a phase I/II trial (study 1108) [see below] in patients with advanced metastatic urothelial bladder cancer^[82].

In March 2020, AstraZeneca reported that the phase III DANUBE trial did not meet the primary endpoint of improving overall survival (OS) versus standard of care chemotherapy (NCT02516241; EudraCT2015-001633-24; D419BC00001). The randomised, open-label study was initiated in November 2015, to assess durvalumab, with or without tremelimumab, in patients with stage IV urothelial bladder cancer. The study enrolled 1126 patients in South Korea, the Netherlands, Spain, Germany, Greece, Israel, Belgium, Poland, Denmark, Brazil, Canada, Italy, Mexico, the US, Australia, Austria, China, Portugal, Japan, Taiwan, Belgium, France, Israel, Russia, Turkey, and the UK^[83]^[80]^[84]. In September 2020, efficacy and adverse events data from the trial were presented at the 45^th European Society for Medical Oncology Congress (ESMO-2020)^[85]. In September 2021, results from the trial were presented at the 46^th European Society for Medical Oncology Congress (ESMO-2021)^[86].

In December 2018, AstraZeneca in collaboration with Canadian Cancer Trials Group initiated a phase II trial to evaluate the trimodality therapy with or without adjuvant durvalumab to treat patients with muscle-invasive bladder cancer (BL13; NCT03768570). The open-label, randomised trial is enrolling approximately 238 patients in Canada^[87].

In April 2023, AstraZeneca and Fundacion CRIS de Investigación para Vencer el Cáncer completed a phase II DUTRENEO trial that evaluated the efficacy of durvalumab and tremelimumab in neoadjuvant bladder cancer patients (NCT03472274; EudraCT2017-002246-68). This open-label, randomised trial was initiated in October 2018 and enrolled 101 patients in Spain. In May 2020, the company presented clinical trial data at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[88]^[89].

In March 2020, the Spanish Oncology Genito-Urinary Group in collaboration with AstraZeneca completed the phase II NEODURVARIB trial that evaluated the combination of durvalumab and olaparib [see Adis Insight drug profile 800024096] as neoadjuvant therapy prior to the surgery for the treatment of patients with advanced urothelial bladder cancer (NCT03534492; SOGUG-2017-A-IEC(VEJ)-2; EudraCT2017-002765-22). The open-label trial was initiated in November 2018, and enrolled 29 patients in Spain^[90].

In November 2018, Spanish Oncology Genito-Urinary Group and AstraZeneca initiated the phase II IMMUNOPRESERVE trial to evaluate the efficacy of durvalumab plus tremelimumab [see ADIS insight drug profile800020650] with concurrent radiotherapy, in terms of pathological response rate, in patients with localised muscle invasive bladder cancer treated with bladder preservation intent (SOGUG2017A-IEC-VEJ1; EudraCT2017-003159-44; NCT03702179). The open label trial intends to enrol approximately 32 patients in Spain^[91]. In June 2021, AstraZeneca presented safety and efficacy data from this study at 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[92].

In February 2012, Memorial Sloan Kettering Cancer Center terminated a phase II trial as no response has been seen in stage 1 (17-511; NCT03430895). The trial was initiated in January 2018 to evaluate the safety and effectiveness of durvalumab combined with tremelimumab in patients urinary tract cancer. The open-label trial enrolled 15 patients, in the US^[93].

In March 2017, M.D. Anderson Cancer Center initiated a pilot pre-surgical clinical trial to assess safety and tolerability of durvalumab in combination with tremelimumab [see AdisInsight drug profile 800020650] in patients with urogenital cancer (2016-0033; NCT02812420). The open-label trial is enrolling approximately 15 patients in the US^[94].

In September 2021, AstraZeneca and H. Lee Moffitt Cancer Center and Research Institute terminated a phase II of durvalumab in patients with urothelial carcinomatrial due to futility. Earlier, AstraZeneca and H. Lee Moffitt Cancer Center and Research Institute, in February 2017, initiated a phase II trial to assess the efficacy of durvalumab in Bacillus Calmette-Guérin refractory patients with urothelial carcinoma in situ of the bladder (MCC-18788; ESR-15-11326; NCT02901548). The open-label, single-group trial enroled 17 patients in the US. In May 2022, data from the study was presented at the117th Annual Meeting of the American Urological Association (AUA-2022)^[95]^[96].

University of California, San Francisco, in collaboration with MedImmune, planned to initiate a phase II trial evaluating safety and efficacy of durvalumab, with or without tremelimumab [see AdisInsight drug profile 800020650], in combination with stereotactic body radiation therapy (SBRT), in patients with unresectable, muscle-invasive or metastatic bladder cancer that are ineligible or refusing chemotherapy (16529; NCT03150836). The randomised, sequential, open-label study will enrol approximately 74 patients, in the US. However, the trial was withdrawn prior to enrolment due to organisational change of the principal investigator^[97].

In August 2021, AstraZeneca completed a phase I BLASST-2 trial which evaluated the effect of durvalumab as a monotherapy and in combination with oleclumab (see Adis Insight drug profile 800042969) as neoadjuvant therapy in patient’s before going for surgery for muscle invasive bladder cancer (18-507; NCT03773666). The open-label trial initiated in February 2019, enrolled 12 patients in the US^[98].

In November 2016, AstraZeneca initiated a phase Ib/II trial, to evaluate safety and efficacy of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab, in patients with urothelial cancer (BTCRC-GU15-023; NCT02891161). The non-randomised, open-label trial will enrol approximately 42 patients in the US^[99].

In March 2018, AstraZeneca initiated the phase II BAYOU trial to determine the efficacy and safety of durvalumab in combination with olaparib [See ADIS Insight Drug Profile 800024096] for first-line treatment in cisplatin-ineligible patients with unresectable stage IV urothelial cancer (NCT03459846; D933IC00003). The double-blind, parallel, prospective, randomised trial is enrolling approximately 256 patients in Taiwan, Spain, Vietnam, Russia, South Korea, the US and Canada^[100].

Acute myeloid leukaemia

Celgene completed the phase II FUSION HR MDS/ELDERLY AML 001 trial in December 2021 which evaluated the safety and efficacy of azacitidine in combination with subcutaneous durvalumab, in patients with acute myeloid leukaemia and those who are at a high risk myelodysplastic syndrome (MEDI4736MDS001; NCT02775903; EudraCT2015-003596-30). The randomised, open-labelled trial was initiated in June 2016 and enrolled 213 patients in Austria, Portugal, Poland, Netherlands, Italy, France, Canada, Belgium, the US, Germany, Spain and the UK. The primary endpoint was overall response rate in both myelodysplastic syndrome and acute myeloid leukaemia cohorts. In December 2019, efficacy and safety data from the trial was presented at the 61^stAnnual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2019)^[101]^[50]^[102].

Biliary tract cancer

In December 2022, European Commission approved Imfinzi (durvalumab) in the European Union (EU) for the first-line treatment of adult patients with unresectable or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin). The approval by the European Commission was based on the primary results from the TOPAZ-1 Phase III trial [see below]^[103]^[104].

In November 2022, the Committee for Medicinal Products for Human Use (CHMP) recommended durvalumab for marketing authorisation in the European Union for the 1st-line treatment of adult patients with un-resectable or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin). The positive opinion was based on the primary results from the TOPAZ-1 phase III clinical trial (see below) ^[105].

In September 2022, US FDA approved durvalumab in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer^[106]. In May 2022, US FDA accepted the supplemental Biologics License Application (sBLA) and granted priority review to durvalumab in combination with standard-of-care chemotherapy, for patients with locally advanced or metastatic biliary tract cancer. The sBLA was based on results from an interim analysis of the phase III TOPAZ-1 trial [see below]^[107].

In December 2022, durvalumab was approved in Japan in combination with tremelimumab [see AdisInsight drug profile 800020650]
plus chemotherapy in patients with curatively unresectable biliary tract cancer.The approval is based on results from an interim analysis of the phase III TOPAZ-1 trial[see below]^[108]. As of September 2022, AstraZeneca announced that as a part of project Orbis durvalumab in combination with chemotherapy (gemcitabine plus cisplatin) is under regulatory review in Australia, Brazil, Canada, Israel, Singapore, Switzerland, UK, Japan and Europe^[109].

In December 2020, the US FDA has granted Orphan Drug Designation (ODD) to durvalumab (IMFINZI) for the treatment of advanced biliary tract cancer (BTC) in the US^[110].

In March 2022, the Therapeutic Goods Administration granted orphan drug designation to durvalumab for the treatment of biliary tract cancer, with lapse date 30/09/2022 (Therapeutic Goods Administration, June 2022).

In July 2022, Durvalumab was assigned category 1 status in the US National Comprehensive Cancer Network (NCCN) guidelines for the First-line treatment of patients with biliary tract cancer, based on the results from the phase III TOPAZ-1 trial^[111]

In July 2023, AstraZeneca initiated phase IIIb TopDouble trial to evaluate durvalumab in combination with gemcitabine-based chemotherapy for the treatment of patients with biliary tract cancer(NCT05924880 ; D933AL00006). The open label trial intends to enroll approximately 115 patients in China^[112] .

AstraZeneca, in April 2019, initiated the phase III TOPAZ-1 study, to evaluate the efficacy of durvalumab or placebo, in combination with gemcitabine/cisplatin, as a first-line therapy in patients with unresectable advanced or metastatic biliary tract cancer, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (D933AC00001; NCT03875235). The primary endpoint of the trial is overall survival within 36 months. The phase III trial recruited 810 patients in the US, Argentina, Bulgaria, Chile, China, France, Hong Kong, India, Italy, Japan, Poland, Russia, South Korea, Taiwan, Thailand, Turkey, and the UK^[104]. The Independent Data Monitoring Committee concluded that the trial met the primary endpoint by demonstrating an improvement in OS in patients treated with durvalumab plus chemotherapy versus chemotherapy alone. The combination also demonstrated an improvement in progression-free survival (PFS) and overall response rate, key secondary endpoints. In October 2021, an Independent Data Monitoring Committee recommended the TOPAZ-1 phase III trial to be unblinded at an interim analysis due to clear evidence of efficacy for durvalumab plus chemotherapy. In October 2021, positive efficacy and adverse events data from the trial were released by the company^[110]. In January 2022, updated efficacy and adverse events data from the trial were released by the company^[113]. In July 2022, data from the trial was released by AstraZeneca^[114] . In June 2022, data from the trial was presented at 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[115]. In September 2022, results from this trial were released by AstraZeneca^[116]. In September 2022, company presented data from the trial at the 47^th European Society for Medical Oncology Congress (ESMO-2022)^[117]^[118]. In October 2023, updated efficacy data from the trial were released by the company at the 48th European Society for Medical Oncology Congress (ESMO-2023)^[119]^[120]. In April 2024, updated results from the phase was released by AstraZeneca^[121].

In March 2022, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest initiated phase II ADJUBIL study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in adjuvant situation for biliary tract cancer (NCT05239169; AIO-HEP-0421/ass). The interventional, prospective multicenter, open-label, randomised, parallel trial intends to enroll approximately 40 patients in Germany^[122].

In November 2018, Multidisciplinary Oncology Cooperative Group in collaboration with AstraZeneca initiated a phase II trial of durvalumab in combination with tremelimumab [see Adis Insight Drug profile 800020650] with or without weekly paclitaxel in patients with advanced biliary tract cancer patients after failure of platinum-based chemotherapy (IMMUNO-BIL; IMMUNO-BIL-D18-1PRODIGE57; NCT03704480). The open-label, randomised trial intends to enrol approximately 102 patients in France^[123]. In June 2022, clinical data was presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[124].

As of July 2022, Seoul National University Hospital completed a phase II trial biomarker-oriented study of durvalumab and tremelimumab [see Adis Insight drug profile 800020650] in combination with gemcitabine/cisplatin in chemotherapy-naïve biliary tract cancer patients (BTC-1st MEDITREME; NCT03046862). The trial was initiated in February 2017 and enrolled 31 patients in South Korea^[125]. In May 2020, results from the trial were presented at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[126]. In June 2022, results from the trial were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[127].

Brain metastases

A phase II trial was terminated due to low accrual, withdrawal of funding by AstraZeneca and change in clinical practice (201602169; NCT02669914; 16-x001). In September 2016, the Washington University School of Medicine and AstraZeneca initiated the trial to investigate the safety and efficacy of durvalumab in patients with brain metastases from epithelial-derived tumours. The parallel, non-randomised, open-label trial recruited four patients in the US^[128].
Breast cancer: In November 2022, Daiichi Sankyo Company in collaboration with AstraZeneca initiated a phase III TROPION-Breast03 trial to evaluate the efficacy and safety of datopotamab deruxtecan with or without durvalumab [see Adis Insight drug profile800051249] when compared with ICT (capecitabine and/or pembrolizumab) in patients with stage I to III TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy (NCT05629585; D926XC00001). The randomized, open label trial intends to enrol 1075 adults and elderly patients in the UK and is expected to expand in Brazil, Canada, Germany, South Korea, Spain, Taiwan, and US^[129]^[130].

In June 2023, AstraZeneca re-initiated the phase II POP-DURVA trial to evaluate the efficacy and safety of preoperative durvalumab in patients with early small (cT1N0) triple negative breast cancer tumors(NCT05215106; EudraCT2020-006106-23; 2020/3210). In October 2022, AstraZeneca suspends a phase II trial. An open-label trial was initiated in December 2021 and intends to enrol approximately 200 participants in France^[131].

In January 2021, AstraZeneca terminated a phase II trial which was evaluating the safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab in postmenopausal patients with hormone-receptor-positive breast cancer, due to lost funding (NCT03874325; ESR-17-13182; MCC-19803). Earlier in April 2019 the trial was initiated, and the open-label trial recruited 17 patients in the US^[132].

In December 2020, AstraZeneca, Gradalis and Mary Crowley Medical Research Center completed a phase II trial which assessed the safety and efficacy of durvalumab 1 500mg IV plus autologous tumour cell vaccine [see AdisInsight drug profile 800029621] in patients with PD-L1 negative locally advanced or metastatic breast cancer and other gynaecological cancers (16-06; CL-PTL 124; ESR-15-11306; NCT02725489). The open-label, parallel, non-randomised trial was initiated in June 2016 and enrolled 13 patients in the US^[133]. In August 2016, Gradalis announced that the first patient has been dosed in the study^[134].

In December 2019, AstraZeneca, in collaboration with Canadian Cancer Trials Group and University Health Network, initiated a phase II trial of orally once daily CFI 400945 and durvalumab IV, in patients with advanced, metastatic triple negative breast cancer (IND.239) (I239; NCT04176848). The open-label trial will enrol approximately 28 patients in Canada^[135].

Jules Bordet Institute and AstraZeneca, in September 2019, initiated the phase II Neo-CheckRay study, to evaluate the safety and efficacy of neoadjuvant chemotherapy and radiotherapy, ±durvalumab and ±oleclumab, in patients with luminal B breast cancer (NCT03875573; EudraCT2018-004165-13; IJB-LBC-NEOCHECKRAY-2018). The multicenter, open label study is expected to enrol approximately 147 subjects in Belgium^[136].

In April 2020, AstraZeneca in collaboration with Institute of Cancer Research, United Kingdom suspended the phase II PHOENIX trial for recruitment due to current public health guidance (NCT03740893; 19LO0127; 40609; ISRCTN 47127434; EudraCT2018-002077-21; ICR-CTSU2017-10065). The trial was initiated in April 2019 to assess whether short exposure to a DNA damage response (DDR) inhibitor and/or anti-PD-L1 immunotherapy in a preoperative WOP in patients with post-NACT high residual disease, generates a signal of anti-tumour biological activity within residual disease tissue. The open-label, randomised trial intended to enrol approximately 81 patients in the UK^[137].

In August 2018, AstraZeneca in collaboration with Kyoto Breast Cancer Research Network terminated a phase II trial that was designed to evaluate the safety and efficacy of durvalumab plus tremelimumab (anti-CTLA-4 antibody drug) [see AdisInsight drug profile 800020650] in combination with hormone therapy (fulvestrant) [see AdisInsight drug profile 800000789] in patients with inoperable or recurrent hormone-receptor-positive and HER2-negative breast cancer with distant metastasis (KBCRN-B-001; R000029938; UMIN000026050; NCT03430466). The trial also intended to investigate immunological biomarkers affecting the therapeutic effect. The trial was initiated in December 2017 and intended to enrol approximately 33 patients in Japan. Response rate based on RECIST criteria was to be evaluated as the primary endpoint^[138].

In September 2018, AstraZeneca, Celgene and German Breast Group completed the phase II GeparNuevo trial which was initiated in March 2016, to evaluate the addition of durvalumab 1.5g IV to chemotherapy(paclitaxel 125 mg/m², epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) in patients with early triple negative breast cancer (GBG89; DRKS00011286; NCT02685059; EudraCT2015-002714-72). The primary endpoint was to compare the pathological complete response (pCR = ypT0 ypN0) rates of neoadjuvant treatment of sequential, nab-paclitaxel followed by EC +/- durvalumab. The randomised, parallel, double-blind, placebo-controlled trial will enrolled 174 patients in Germany. In June 2021, efficacy results were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (AACR-2021)^[139]^[140].

In July 2018, MedImmune and the Northwestern University re-initiated participant recruitment in a phase II trial that was designed to assess the efficacy of durvalumab in combination with tremelimumab [see AdisInsight drug profile 800020650] for the treatment of patients with metastatic HER2-negative breast cancer. In September 2017, the recruitment in the trial was suspended (NU 15B01; NCI-2015-01445; ESR-14-10694; D4190C00030; STU00200984; P30CA060553; NCT02536794). The response rate evaluated as stable disease for ≥12 weeks, partial response or complete response as evaluated by the RECIST version 1.1 were to be evaluated as primary endpoint measure in the trial. The open-label, single-group assignment trial was initiated in December 2015 and intended to enrol approximately 30 patients in the US^[141].

In June 2018, AstraZeneca in collaboration with Seoul National University Hospital initiated a phase I/II trial to evaluate the combination therapy olaparib [See AdisInsight drug profile 800024096] and durvalumab (MEDI4736) before standard neoadjuvant chemotherapy for stage II/III triple negative or low ER+ breast cancer (NCT03594396; S1709-101-888). The open-labelled trial is designed to enroll approximately 54 patients in South Korea. In December 2021, results from the trial were presented at the 44th annual San Antonio Breast Cancer Symposium (SABCS-2021)^[142]^[143].

In December 2020, AstraZeneca and Daiichi Sankyo Company initiated the phase I/II DESTINY-Breast07 trial to assess the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) [see Adis Insight drug profile 800043383] in combination with durvalumab and other anti-cancer agents in patients with HER2-positive metastatic breast cancer (D967JC00001; NCT04538742). The open-label, randomised trial intends to enrol approximately 450 patients in the US, Australia, Brazil, Canada, France, Germany, India, Italy, South Korea, Poland, Russia, Spain, Taiwan, Turkey and the UK^[144]. In June 2022, the company presented pooled safety data from the phase I/II and phase Ib trial (see below) at the 58^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[145].

In December 2018, AstraZeneca initiated the phase Ib/II BEGONIA trial to determine the efficacy and safety of durvalumab in combination with paclitaxel and multiple novel oncology therapies and durvalumab with paclitaxel alone for the treatment of first-line metastatic triple negative breast cancer (NCT03742102; D933LC00001). The open-label, randomised trial is enrolling approximately 240 patients in the US, Canada, South Korea, Poland, Taiwan and the UK^[146]. In June 2021, the company presented safety and efficacy data from the trial at the 57^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[147]. In December 2021, the company presented updated results of the trial at the 44th Annual San Antonio Breast Cancer Symposium (SABCS-2021)^[148]. In December 2022, Daiichi Sankyo Company released updated results from the study^[129]. Updated efficacy and safety data from a phase I/II trial in Breast cancer presented at the 45^th Annual San Antonio Breast Cancer Symposium (SABCS-2022)^[149]. In October 2023, AstraZeneca presented adverse events and efficacy data from the trial at the 48^th European Society for Medical Oncology Congress (ESMO-2023)^[150].

In March 2020, AstraZeneca in collaboration with King Faisal Specialist Hospital and Research Center completed a phase I/II trial that evaluated the safety, tolerability and efficacy of durvalumab in combination with paclitaxel in patients with metastatic triple negative PD-L1 positive breast cancer (2151-169; ESR-14-10649; NCT02628132). The open-label trial was initiated in July 2016 and enrolled 22 patients in Saudi Arabia. In September 2019, results from the trial were presented at the 44th European Society for Medical Oncology Congress (ESMO-2019)^[151]^[152].

Grand Hopital de Charleroi initiated the B-IMMUNE phase I/II trial to assess the safety and tolerability of durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer (ONCOGHdC2015-01; EudraCT2016-003998-17). This open, prospective, randomised is enrolling 57 patients in Belgium^[153].

In November 2015, Yale university initiated a phase I/II neoadjuvant trial to assess the safety of durvalumab combined with chemotherapy and determine if full dose of durvalumab can be administered concomitantly with full dose weekly nab-paclitaxel followed by dose-dense AC chemotherapies (ddAC), respectively, for the treatment of breast cancer (1409014537; NCT02489448). The phase II portion will evaluate the pathologic complete response (pCR) rate with durvalumab in combination with weekly nab-paclitaxel x 12 treatments followed by durvalumab in combination with ddAC x 4 treatments for estrogen receptor (ER), progesterone receptor (PR) and HER2 negative (triple negative, TNBC) breast cancer. The open-label, single-group assignment trial will enrol 61 patients in the US. In June 2017, Yale university presented safety data of the trial at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO-2017)^[154]^[155]. In June 2022, results from the trial were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[156]. In December 2022, data from the trial were presented at the 45th Annual San Antonio Breast Cancer Symposium (SABCS-2022)^[157].

In December 2023, Washington University School of Medicine in collaboration with MedImmune LLC terminated a phase I trial due to insufficient funding and unavailability of drugs and equipment. The trial was intended to compare the safety and efficacy of neoantigen DNA vaccine [see ADIS insight drug profile800049779] alone and neoantigen DNA vaccine in combination with durvalumab plus carboplatin plus etoposide, in triple negative breast cancer (TNBC) patients following standard of care therapy (201710109; NCT03199040). The open label trial was initiated in April 2018 and enrolled 18 patients in the US^[158].

In December 2020, Astra Zeneca and Daiichi Sankyo initiated the phase Ib DESTINY-Breast08 trial to evaluate the efficacy, safety, tolerability, pharmacokinetics, and preliminary anti-tumour activity of trastuzumab deruxtecan [see Adis Insight Drug profile 800043383] in combination with other therapies such as capecitabine [see Adis Insight Drug profile 800006401], capivasertib [see Adis Insight Drug profile 800018391], durvalumab, paclitaxel, anastrozole, and fulvestrant, in patients with metastatic HER2-low advanced or metastatic breast cancer (NCT04556773; DB-08; D967JC00002). In addition to safety and tolerability, this study will also assess ORR, PFS, DoR, and OS for each treatment combination. The multicentre, open, parallel, prospective, non-randomised trial intends to recruit 182 patients in the US, Australia, Belgium, Brazil, Canada, France, South Korea, Mexico, Russia, and Taiwan^[159].

In February 2020, AstraZeneca in collaboration with Icahn School of Medicine at Mount Sinai completed a phase I trial that evaluated the safety and tolerability of durvalumab in combination with eribulin [see ADIS Insight Drug profile 800015511] in patients with HER2-negative metastatic breast cancer and recurrent ovarian cancer (GCO17-2320; NCT03430518). The open-label trial was initiated in May 2018 and enrolled 12 patients in the US. The safety and efficacy results were presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) in May 2020^[160]^[161].

In June 2017, University of Texas M.D. Anderson Cancer Center in collaboration with AstraZeneca, initiated a pilot, pre-surgical, phase I trial to evaluate the highest dose combination of durvalumab and tremelimumab in patients with HR+, HER2- breast cancer. The open-label trial is designed to enrol approximately 15 patients in the US^[162].

In August 2016, Massachusetts General Hospital in collaboration with OncoPep and AstraZeneca, initiated a phase Ib trial to assess the safety, tolerability and immune response of intramuscularly administered PVX 410 vaccine [see AdisInsight drug profile 800035618] (mixed with poly-ICLC adjuvant) alone and in combination with durvalumab intravenous infusion, in human leukocyte antigen (HLA)-A2+ patients following standard treatment of stage II or III triple negative breast cancer (16-132; NCT02826434). The open-label, single-group trial will enrol approximately 20 patients in the US ^[163]^[164]. In December 2019, safety and immunogenicity data from the trial was presented at the 42nd Annual San Antonio Breast Cancer Symposium (SABCS-2019)^[165].

In November 2019, The Canadian Cancer Trials Group in collaboration with AstraZeneca completed a phase Ib, pharmacodynamic study of durvalumab in adjunction with trastuzumab in patients with advanced/metastatic/recurrent or unresectable HER-2 positive metastatic breast (I229; NCT02649686). The primary endpoint of the study was to establish the recommended phase II dose. The open-label trial was initiated in April 2016 and enrolled 15 patients in Canada^[166]. In June 2018, the company presented safety and efficacy data of the combination therapy at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[167].

Cervical and vulvovaginal cancer

In July 2023, AstraZeneca completed a phase III CALLA trial that was designed to evaluate the efficacy and safety of durvalumab in combination with chemoradiotherapy to be compared with chemoradiotherapy alone in the treatment of locally advanced cervical cancer (D9100C00001; NCT03830866; EudraCT2018-002872-42). The randomised, double-blind, trial was initiated in February 2019 and enrolled 770 patients in South Africa, Brazil, Chile, China, Hungary, India, Japan, Peru, Mexico, Philippines, Poland, Russia, South Korea, Taiwan and US^[168].

In November 2020, MedImmune and Advaxis terminated a phase I/II trial to evaluate durvalumab alone and in combination with axalimogene filolisbac [see AdisInsight drug profile 800025081] in patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer (ADXS001-04; NCT02291055). The phase I portion was designed to identify a recommended dose regimen for the combination therapy, and the phase II portion evaluated the safety and efficacy of the combination. The open-label, randomised study was initiated in April 2015 and enrolled 75 patients in the US^[169]. In July 2016, dosing of patients in second-dose escalation cohort was completed and commenced enrolment in the the part A expansion and part B portion of the trial. The part A expansion portion of the trial intends to enrol approximately 20 patients with HPV associated head and neck cancer, who will receive 1x10⁹ cfu in combination with durvalumab (10 mg/kg). The part B portion of the trial intends to enrol approximately 45 patients, who will receive same dosage of the combination^[170]. In March 2016, Advaxis and MedImmune completed the first dose-escalation cohort of 1x10⁹ cfu with 3 mg/kg durvalumab and commenced the second dose-escalation cohort of 1x10⁹ cfu in combination with 10 mg/kg durvalumab in the study^[171]. In November 2014, Advaxis submitted an IND to the US FDA for the phase I/II trial of axalimogene filolisbac alone or in combination with MedImmune's durvalumab for the treatment of advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck cancer. Preclinical data suggested that the combination of these two products will enhance overall anti-tumour response. The US FDA will notify Advaxis within 30 calendar days of any questions relates to the trial protocol. The two companies entered into a collaboration in July 2014 to conduct the trial^[172]^[37].

In July 2018, M. D. Anderson Cancer Center and AstraZeneca initiated a phase I trial to evaluate durvalumab and tremelimumab in combination with radiotherapy for treatment of patients with recurrent or metastatic advanced cervical, vaginal or vulvar cancer (2017-0548; NCI-2018-00627; NCT03452332). The open-label trial is designed to enrol approximately 18 patients in the US^[173].

In December 2017, AstraZeneca initiated the phase I DURVIT study of durvalumab in cervical cancer patients who are scheduled for lymph node dissection or lymph node debulking in the context of a radical hysterectomy or chemo-radiation (ESR16-11856Astra-Zeneca; NTR6119; NL59122-018-16ABR; 25490). The non-randomised, single-arm, open-label study is enrolling approximately 24 patients in the Netherlands^[174].

Chronic lymphocytic leukaemia

In August 2022, Celgene completed phase-I/II trial that evaluated efficacy, pharmacokinetics, pharmacodynamics, safety and tolerability of durvalumab 1 500mg IV infusion both alone and as a combination therapy in patients with chronic lymphocytic leukaemia and certain lymphoma subtypes (FUSION NHL 001; MEDI4736-NHL-001; NCT02733042). In September 2017, the US FDA placed a partial clinical hold on a phase I/II trial which was evaluating efficacy, pharmacokinetics, pharmacodynamics, safety and tolerability of durvalumab 1 500mg IV infusion both alone and as a combination therapy in patients with chronic lymphocytic leukaemia and certain lymphoma subtypes (FUSION NHL 001; MEDI4736-NHL-001; NCT02733042). The hold was based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48]. The study had 3 parts: dose finding, dose confirmation and dose expansion. The open-label, non-randomised trial initiated in May 2016, and enrolled 106 patients in France, Italy, Japan, the Netherlands, the US, the UK, and Germany^[47]^[50]^[175].

Colorectal cancer

As of January 2023, AstraZeneca and Medimmune in collaboration with European Organisation for Research and Treatment of Cancer discontinued a phase II trial which evaluated the efficacy of tremelimumab [see adisinsight drug profile 800020650] in combination with durvalumab in patients with incurable liver metastases from colorectal cancer due to the futility of the study (NCT03101475; 1560-GITCG; EudraCT2017-001375-22). The open-label phase II study was initiated in November 2018 and enrolled 22 patients in Austria, France, Germany, Netherlands, Sweden and Switzerland^[176].

In June 2022, VHIO Vall d’Hebron Institute of Oncology in collaboration with AstraZeneca initiated a phase II trial to assess the antitumor activity of durvalumab or tremelimumab [see adisinsight drug profile 800020650] 300 mg single dose followed by durvalumab in patients with microsatellite instable (MSI) colorectal cancer (CRC) or endometrial cancer (EC) and tremelimumab 300 mg single dose followed by durvalumab in refractory microsatellite stable (MSS) (EudraCT2021-004061-13; ESR21-21165). The randomized, open-label trial aims to enroll 60 patients in Spain.

In October 2020, Cancer Research UK in collaboration with University of Glasgow, AstraZeneca, and NHS Greater Glasgow and Clyde initiated a phase II PRIME-RT trial to investigate whether the addition of durvalumab to FOLFOX chemotherapy and radiation treatment (either SCRT or LCRT) in a neoadjuvant setting for patients with locally advanced rectal cancer (LARC) improves rates of complete response (EudraCT2019-001471-36; NCT04621370; PrimeRT2018; CPMS47412IRAS256921; 20ES0083; 18138369). The open, parallel, prospective, randomized trial intends to recruit 54 patients. Enrolment has initiated in the UK in October 2020. The trial is expected to expand to other locations^[177].

In March 2018, M.D. Anderson Cancer Center in collaboration with MedImmune, AstraZeneca and Novartis initiated a phase II trial to evaluate the efficacy and safety of trametinib [see ADIS insight drug profile800024261] and durvalumab, in patients with metastatic colorectal cancer (2017-0514; NCT03428126). Evaluation of the maximum tolerated dose and best overall response are the defined primary endpoints of the trial. The open label trial intends to enrol approximately 56 patients in the US^[178].

In August 2022, AstraZeneca and Biocompatibles International suspended enrollments in a phase I/II iRE-C trial, as they are working on revisions. The trial was designed to evaluate the feasibility and safety of fixed dose of durvalumab (750 mg) in combination with Yttrium-90 radioembolization (Y90-RE) for the treatment of subjects with liver-predominant, metastatic colorectal cancer (mCRC), which is mismatch repair proficient/microsatellite stable (pMMR/MSS) (201909709; NCT04108481). The open, prospective trial was initiated in October 2020 and intended to enroll approximately 18 patients in the US^[179].

Prior to September 2020, Medimmune withdrew its planned phase II COLUMBIA-2 trial prior to enrollment initiation due to changing standard of care landscape. The trial was designed to evaluate the safety and efficacy of standard of care (FOLFOX) alone and in combination with novel oncology therapies, monalizumab (see AdisInsight drug profile 800034739) and durvalumab and oleclumab (see AdisInsight drug profile 800042969) in patients with high-risk microsatellite-stable colorectal cancer (D910CC00002; NCT04145193). The open-label, randomised trial was intended to enrol patients in Australia, Canada, France, South Korea, Spain, Taiwan and in the US^[180].

In January 2023, AstraZeneca completed phase I/IIa MEDITREME trial to evalute the safety, tolerability and immunological activity of of durvalumab (750 mg/q2W), in combination with tremelimumab (75 mg/q4W) and FOLFOX (6 cycles), in patients with previously untreated RAS-mutated metastatic colorectal cancer (mCRC) (NCT03202758; MEDI-TREME-COLON). The treatment will be administered as an induction therapy followed by maintenance therapy with durvalumab. The open-label study which was initiated in August 2017cand enrolled 57 patients in France^[181]. In September 2021, efficacy and safety results from the trial were presented at the 46th European Society for Medical Oncology Congress (ESMO-2021)^[182].

In April 2021, Memorial Sloan Kettering Cancer Center, MedImmune and AstraZeneca completed a phase II trial that was designed to evaluate the safety and efficacy of durvalumab and tremelimumab [see AdisInsight drug profile 800020650] given in combination with radiation therapy or ablation (17-139; NCT03122509). This non-randomised, parallel trail initiated in April 2017, enrolled 25 patients in the US^[183].

In June 2022, AstraZeneca and Canadian Cancer Trials Group completed a phase II trial which was designed to assess the safety and efficacy of tremelimumab [see AdisInsight drug profile 800020650] in combination with durvalumab and best supportive care (BSC) versus BSC alone in patients with refractory, advanced and unresectable colorectal adenocarcinoma (CO26; NCT02870920). The randomized, open-label, parallel trial initiated in August 2016, enrolled 180 patients in Canada^[184]. In June 2022, Canadian Cancer Trials Group presented results from the trial at the 58^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[185].

In June 2020, AstraZeneca, MedImmune and Memorial Sloan-Kettering Cancer Center completed a phase II trial of durvalumab for the treatment of colorectal cancer (14-109; NCT02227667). The trial evaluated the efficacy of durvalumab in immunological subsets of refractory metastatic colorectal cancer. The open-label, single-arm study was initiated in October 2014 and enrolled 16 participants in the US^[186].

In July 2017, NSABP Foundation initiated a phase II trial to evaluate the safety and efficacy of tremelimumab and durvalumab following hypofractionated palliative radiation in patients with microsatellite stable metastatic colorectal cancer (NSABP FC-9; ESR-15-11514; NCT03007407). The open-label, single-group trial will enrol approximately 21 patients in the US. Results from the trial were presented at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[187]. In March 2019, Astra-Zeneca initiated presented updated results from the trial at the 110th Annual Meeting of the American Association for Cancer Research (AACR-2019)^[188]^[189].

In January 2023, MedImmune and M.D. Anderson Cancer Center, completed a pilot phase I trial that evaluated the safety and efficacy of neoadjuvant use of tremelimumab [see AdisInsight drug profile 800020650] in combination with durvalumab, FOLFOX (fluorouracil, leucovorin, and oxaliplatin) and bevacizumab in patients with resectable colorectal cancer with liver metastases (2015-0828; NCT02754856). The open-label, single-group trial, initiated in July 2016, enrolled 22 patients in the US^[190].

Diffuse large B cell lymphoma

In April 2022, Celgene completed a phase II trial that investigated the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma (NCT03003520; MEDI4736-DLBCL-001; EudraCT2015-005173-20). Earlier, in September 2017, the US FDA placed a partial clinical hold on the study based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48]. The open-label trial initiated in December 2016 and enrolled 46 patients in Estonia, Austria, Denmark, the US and in the UK ^[47]^[191].

Pharmacyclics and AstraZeneca initiated a phase I/II trial to evaluate safety and tolerability of ibrutinib in combination with durvalumab, in patients with relapsed or refractory diffuse large B cell lymphoma, in May 2015 (PCYC1136CA; NCT02401048) [see AdisInsight drug profile 800037095]. The phase I portion of the study is designed to determine the appropriate dose of ibrutinib when administered in combination with durvalumab. The phase II portion is expected to assess the safety and effectiveness of the combination treatment. The open-label study is intended to enrol 109 patients in the US^[192]^[193].

AstraZeneca and Gilead are planning to initiate a phase I/II study to investigate the safety and efficacy of durvalumab in combination with idelalisib [see AdisInsight drug profile 800025920] in patients with haematological cancers/solid tumours including diffuse large B-cell lymphoma and triple negative breast cancer^[28]^[194].

In November 2018, AstraZeneca in collaboration with Austin Health initiated the phase I RaDD dose escalation study of radiotherapy and durvalumab in relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) (ONJ2017-003DV008259; TRP16-006; NCT03610061). The open-label trial is enrolling approximately 36 patients in Australia^[195].

In February 2019, MedImmune (a subsidiary of AstraZeneca) completed a phase I trial that determined the maximum tolerated dose, identify dose-limiting toxicities, and assessed the safety, tolerability and efficacy of durvalumab alone and in combination with either tremelimumab [see AdisInsight drug profile 800020650] or AZD 9150 [see AdisInsight drug profile 800021483] in adult patients with relapsed or refractory diffuse large B-cell lymphoma, previously treated with ≤ two prior lines of therapy, including at least 1 rituximab-containing chemotherapy regimen (D4190C00023; NCT02549651). The randomised, open-label, parallel trial was initiated in July 2016 and recruited 32 patients in the US, Italy, Ireland, France and the UK^[196].

Endometrial cancer

In May 2020, AstraZeneca initiated a phase III DUO-E trial to evaluate the efficacy and safety of durvalumab in combination with platinum-based chemotherapy followed by maintenance durvalumab with or without olaparib (see AdisInsight drug profile 800024096) in newly diagnosed patients with advanced or recurrent endometrial cancer (D9311C00001; ENGOT-EN10; EudraCT2019-004112-60; GOG3041; NCT04269200). The randomised, double-blind trial intends to enrol approximately 699 patients in the US, Belgium, Greece, Australia, Brazil, Canada, China, Colombia, Estonia, Germany, Hong Kong, Hungary, India, Israel, Japan, Lithuania, Mexico, Poland, Russia, Singapore, South Korea, and Spain^[197]. In October 2023, clinical data was released by AstraZeneca^[198]. In October 2023, updated efficacy and adverse events data from the trial were released by the company at the 48th European Society for Medical Oncology Congress (ESMO-2023)^[199].

In July 2019, AstraZeneca initiated a phase II trial to evaluate the efficacy of combination therapy of olaparib tablets and durvalumab IV, in patients with advanced endometrial cancer or carcinosarcoma of the uterus (DOMEC; NCT03951415). The open label trial intends to enrol approximately 55 patients in Netherlands^[200].

In December 2021, AstraZeneca and University of Sydney completed the phase II PHAEDRA trial which was evaluating the safety and efficacy of durvalumab in patients with advanced endometrial cancer (371527; U1111-1186-8932; ANZGOG1601Australia-New-Zealand-Gynaecological-Oncology-Group; X16-0346amp-HREC16RPAH472; ACTRN12617000106336). In February 2017, the trial was initiated, and the evaluation of the objective tumour response rate was the primary endpoint of the trial. The open-label, non-randomised trial enrolled 71 patients in Australia^[201].

Gastric cancer

In November 2020, AstraZeneca initiated the phase III MATTERHORN trial of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab in patients with resectable gastric and gastroesophageal junction cancer (GC/GEJC) (NCT04592913; EudraCT2019-001555-40; D910GC00001). The randomised trial intends to enrol approximately 948 participants in United Kingdom, Argentina, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Hungary, Japan, South Korea, Netherlands, Peru, Poland, Russia, Spain, Taiwan, Turkey and the US^[202]. In October 2023, the company released data from the trial. In October 2023, results form this trial were released by AstraZeneca^[203]^[204]

In November 2018, AstraZeneca and Seoul National University Hospital initiated a biomarker-oriented phase II trial to investigate the safety and efficacy of durvalumab in combination with olaparib and paclitaxel in patients with advanced, unresectable or recurrent gastric cancer (NCT03579784; ESR-15-11655). The open-label, single-group trial is recruiting approximately 40 patients in South Korea^[205].

In November 2016, AstraZeneca and Memorial Sloan Kettering Cancer Center initiated a pilot phase Ib/II trial to investigate the safety and efficacy of durvalumab addition to chemoradiation (carboplatin and paclitaxel) in patients with adenocarcinoma of the oesophagus or gastroesophageal junction (16-1405; NCT02962063). The open-label, single-group trial is recruiting 35 patients in the US^[206]. In June 2022, final results from the study were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[207].

In October 2022, Medimmune completed the phase Ib/II COLUMBIA-1 trial that evaluated the safety and efficacy of standard of care (FOLFOX plus bevacizumab) alone plus durvalumab in combination with oleclumab [see Adis insight drug profile800042969] in first-line metastatic microsatellite-stable colorectal cancer (MSS-CRC) (D910CC00001; NCT04068610). The randomised, open-label trial was initiated in September 2019 and recruited 61 patients in the US, Australia, Canada, France and Spain^[208]. In February 2022, , Medimmune decided to terminate the clinical study because superior efficacy was not observed for the novel study drug combinations under investigation.

In April 2019, MedImmune completed a randomised, open-label phase Ib/II trial of durvalumab in combination with tremelimumab, versus durvalumab monotherapy and tremelimumab monotherapy, as second- or third-line therapy in patients with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma (D4190C00021; NCT02340975). The trial was initiated in March 2015 and enrolled 114 patients in the US, Japan, South Korea, Singapore, Taiwan and Canada. In June 2018, results from the trial were presented at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[209]^[210]. Additional safety and efficacy results from the trial were presented at the 110^th Annual Meeting of the American Association for Cancer Research (AACR-2019)^[211].

Head and neck cancer

In November 2019, Hellenic Cooperative Oncology Group in collaboration with AstraZeneca completed a phase II OPHELIA trial of olaparib [see Adis insight drug profile 800024096] in combination with cisplatin, olaperib in combination with durvalumab and olaparib alone before starting standard treatment in patients with squamous-cell carcinoma of head and neck (NCT02882308; EudraCT2015-005268-41; HE5A/15). The randomised, open-label trial was initiated in October 2016 and enrolled 41 patients in Greece^[212].

AstraZeneca, in November 2016, announced that the US FDA had lifted the partial clinical hold on the enrolment of new patients with head and neck squamous cell carcinoma (HNSCC) for clinical trials of durvalumab as a monotherapy and in combination with tremelimumab or other potential medicines. Consequently, AstraZeneca resumed enrolment for all head and neck cancer trials globally. The US FDA placed a partial hold on the enrolment of new patients with head and neck cancer in October 2016. AstraZeneca submitted a detailed analysis of adverse events related to bleeding observed during phase III KESTREL and EAGLE trials to FDA to facilitate the re-initiation of patient enrolment^[213]^[214].

AstraZeneca intends to file durvalumab for approval for the second-line treatment of PD-L1-positive head and neck cancer in the US. The product has received fast track designation from the US FDA. Filings in the EU and Japan are planned for this indication, and will be supported by the results of the pivotal HAWK trial^[215].

In November 2020, AstraZeneca completed the phase III EAGLE trial that evaluated the safety and efficacy of durvalumab in combination with tremelimumab, compared with the standard of care, in patients with recurrent or metastatic, PD-L1-positive or negative squamous cell head and neck cancer (D4193C00002; NCT02369874; EudraCT2014-003863-40). The open label trial was initiated in September 2015 and enrolled 736 patients in the US, Hungary, France, Poland, Belgium, Bulgaria, Czech Republic, Italy, Ukraine, Serbia, Croatia, Brazil, Argentina Japan, South Korea, Romania, Russia, Spain, Germany, Australia, Chile, Israel and Taiwan. The enrolment was suspended in October 2016, and was re-initiated subsequently. In December 2018, Astrazeneca reported that the phase III EAGLE trial did not meet the primary endpoints of improving overall survival (OS) compared to standard-of-care (SoC) chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma and safety and tolerability profiles for durvalumab monotherapy and durvalumab in combination with tremelimumab were consistent with previous studies. In June 2019, the results from the trial were presented at the 55th Annual Meeting of the American Society of Clinical Oncology, ASCO-2019^[216]^[217]^[76]^[218].

In May 2020, AstraZeneca presented pooled results from four studies, including 1108, CONDOR, HAWK [see below] trials and EAGLE [see above] trial, in 467 patients with head and neck squamous cell carcinoma at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[219]^[220]^[221]^[222]^[218].

In May 2021, AstraZeneca completed the phase III KESTREL trial to determine the safety and efficacy of durvalumab alone or in combination with tremelimumab [see AdisInsight drug profile 800020650], compared with the standard of care in patients with recurrent or metastatic squamous cell head and neck cancer (NCT02551159; CTRI2016-08-007169; DRKS00010227; JapicCTI153107; D419LC00001; EudraCT2015-003589-10). The randomised, open-label trial initiated in October 2015 and completed enrolment of 823 patients in December 2017 in Vietnam, Ukraine, Thailand, Taiwan, Spain, Slovakia, Russia, Romania, Portugal, Poland, Philippines, South Korea, Japan, Italy, India, Greece, Germany, Canada, Austria, France, Belgium, Brazil and Bulgaria, the US, and the UK. In February 2021, AstraZeneca announced that the phase III KESTREL trial did not meet the primary endpoint of improving overall survival (OS) versus the EXTREME treatment regimen (chemotherapy plus cetuximab), in the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumours expressed high levels of PD-L1. Also, the combination of durvalumab plus tremelimumab did not indicate an OS benefit in patients, and safety and tolerability profiles for durvalumab monotherapy and durvalumab in combination with tremelimumab were consistent with previous studies^[223]. The primary endpoint of the trial is progression-free survival and overall survival up to 3 years of therapy. The enrolment was suspended in October 2016, which was then re-initiated^[76]^[224].

In September 2018, University of Erlangen-Nürnberg Medical School initiated a phase II CheckRad-CD8 trial to evaluate combination of durvalumab + tremelimumab + radiotherapy as first line treatment of locally advanced head and neck squamous cell carcinoma (EudraCT2017-003226-3; NCT03426657). The label trial intends to enrol approximately 120 patients in Germany^[225]. Efficacy, safety and immunogenicity data from the trial were released at the 44^th European Society for Medical Oncology Congress (ESMO-2019)^[226]. Later, in May 2020, results from the trial were also presented at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020). In June 2021, safety and efficacy data from the trial were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[227]^[228].

In August 2018, Charite Universitätsmedizin Berlin and AstraZeneca initiated the phase II DuTRe-raD trial to evaluate the feasibility and efficacy of durvalumab plus tremelimumab in combination with radiotherapy and durvalumab in combination with radiotherapy as first-line therapy for patients with non-resectable locally advanced HPV negative HNSCC- A COMPARISON WITH A HISTORICAL CONTROL GROUP (CCCC-H&N-IRT-1; EudraCT2016-003175-22; NCT03624231). The two-arm, randomised trial is recruiting 120 patients in Germany^[229]. In May 2020, safety results from the trial were presented at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[230]. In June 2023, updated data were presented at the 59^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023)^[231].

In December 2017, AstraZeneca and Celgene in collaboration with UNC Lineberger Comprehensive Cancer Center initiated a phase II trial to evaluate the multimodality therapy with induction carboplatin/nab-paclitaxel/durvalumab followed by surgical resection and risk-adapted adjuvant therapy for the treatment of locally-advanced and surgically resectable squamous cell carcinoma of the head and neck (NCT03174275; LCCC1621). The open, parallel trial is enrolling approximately 39 patients in the US^[232].

Prior to June 2021, Samsung Medical Center completed a phase II trial in patients with recurrent or metastatic head and neck squamous cell carcinoma (NCT03450967; 2017-09-026). Earlier in March 2018, Samsung Medical Center initiate the phase II clinical trial to evaluate the efficacy of durvalumab plus tremelimumab [see AdisInsight RDI 800020650] combined with proton therapy given in patients with recurrent or metastatic head and neck squamous cell carcinoma. The trial enrolled 31 patients in South Korea^[233].

In March 2021, Medimmune completed a phase Ib/II trial which evaluated the safety and efficacy of MEDI 0457 [see Adis Insight Drug profile800039306], plus durvalumab in patients with HPV-associated recurrent/metastatic head and neck cancer (NCT03162224; D8860C00005). The trial was initiated in June 2017 and enrolled 35 participants in the US. In August 2019, Inovio Pharmaceuticals announced that the study completed enrollment of 50 patients in the US. Earlier in January 2018, Inovio Pharmaceuticals reported that the phase I safety review portion of the study had been completed and the phase II efficacy stage of the trial had begun. This initiation of the phase II part of the trial triggered a milestone payment to Inovio Pharmaceuticals from Astra Zeneca^[234]^[235]^[236]. In September 2020, efficacy and adverse events data from the trial were presented at the 45^th European Society for Medical Oncology Congress (ESMO-2020)^[237].

In July 2020, AstraZeneca, in collaboration with PRA Health Sciences completed the phase II HAWK trial that evaluated the efficacy of durvalumab monotherapy as second-line therapy in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck (D4193C00001; NCT02207530; EudraCT014-003295-23). The open-label, single-arm study was initiated in October 2014 and enrolled 112 patients in the US, Canada, the UK, Belgium, Czech Republic, France, Germany, Hungary, Israel, Georgia, South Korea, Malaysia, Taiwan and Spain (AstraZeneca pipeline, February 2017)^[238]^[215]^[222].

In July 2020, AstraZeneca, in collaboration with PRA Health Sciences completed the phase II CONDOR trial that evaluated the efficacy and safety of durvalumab monotherapy, tremelimumab monotherapy and durvalumab + tremelimumab combination therapy, in patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck and who have progressed during or after treatment with a platinum-containing regimen (D4193C00003; NCT02319044; EudraCT2014-003717-29). The open-label, randomised trial was initiated in April 2015, and enrolled 267 patients in the US, the UK, Belgium, Canada, Czech Republic, France, Georgia, Germany, Hungary, South Korea, Malaysia, Taiwan, Australia, Israel and Spain (AstraZeneca pipeline, February 2017). Data from the study were anticipated in the first half of 2017. In February 2018, safety and efficacy data from the trial were released by the company^[215]^[238]^[221].

In May 2020, AstraZeneca presented pooled results from two phase II studies, including CONDOR and HAWK trials [see above] in patients with head and neck squamous cell carcinoma at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[239]^[221]^[222].

In December 2021, AstraZeneca in collaboration with Radboud University completed the phase I/II PINCH trial to evaluate the non-invasive imaging of tumour PD-L1 expression with 89Zr-labeled durvalumab PET/CT predicting response to durvalumab (NCT03829007). Previously in December 2020, the trial had been terminated due to hampered patient enrolment after registration of first-line pembrolizumab. The open-label trial was initiated in April 2019 and enroled 33 patients in the Netherlands^[240]. Later, in May 2020, results from the trial were presented at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[241].

In February 2022, AstraZeneca terminated the phase I/II trial due to lack of efficacy in study treatment which evaluated the safety and tolerability of durvalumab and tremelimumab [see Adis Insight drug profiles 800020650 ] and palliative radiation therapy in patients with recurrent metastatic squamous cell carcinomas of the head and neck previously exposed to an anti PD-1 or PDL-1 monoclonal antibody (9881; NCI2018-00540; NCT03522584; P30CA015704; RG1717067). The open label trial was initiated in May 2018, enrolled 6 patients in USA^[242]

In July 2018, AstraZeneca, in collaboration with Centre hospitalier de l'Université de Montréal, initiated a phase I/II trial to evaluate durvalumab plus tremelimumab plus stereotactic body radiotherapy for metastatic head and neck carcinoma (NCT03283605; ESR16-12361). The open-label trial is enrolling approximately 45 patients in Canada^[243]. In May 2020, the Centre Hospitalier de l'Universite de Montreal presented initial results from this trial at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[244]. In June 2023, updated clinical data from this trial was presented at 59^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023)^[245].

In August 2020, AstraZeneca in collaboration with MedImmune, terminated a phase II trial designed to assess the safety, pharmacokinetics and preliminary anti-tumour activity of durvalumab in combination with AZD 9150 or AZD 5069 [see AdisInsight drug profiles 800021483 and 800030696] in patients with advanced solid malignancies (D5660C00004; NCT02499328) (AstraZeneca pipeline, August 2020). The randomised, open-label trial initiated in August 2015, intended to enrol 339 patients in Belgium, Germany, Italy, Spain, United Kingdom, and the US ^[246]. Data from treatment-naive patients with head and neck cancer, administered with the combination of durvalumab and AZD 9150, were released by Ionis Pharmaceuticals in September 2017^[247]. Early results from the trial were presented at the 41^st European Society for Medical Oncology Congress (ESMO-2016)^[248]. Updated results from the trial were presented at 43rd European Society for Medical Oncology Congress (ESMO-2018) in October 2018^[249]^[250].

In March 2017, AstraZeneca and Massachusetts General Hospital initiated the phase Ib/II Rescue trial to assess the safety and efficacy of durvalumab in combination with decitabine patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who have progressed on anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy (16-425; NCT03019003). The open-label, non-randomised, single-group trial will enrol approximately 13 patients in the US^[251].

In November 2020, MedImmune and Advaxis terminated a phase I/II trial which evaluated durvalumab alone and in combination with axalimogene filolisbac [see AdisInsight drug profile 800025081] in patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer (ADXS001-04; NCT02291055). The phase I portion identified a recommended dose regimen for the combination therapy, and the phase II portion evaluarted the safety and efficacy of the combination. The open-label, randomised study enrolled 75 patients in the US^[169]. In November 2014, Advaxis submitted an IND to the US FDA for the phase I/II trial of axalimogene filolisbac alone or in combination with MedImmune's durvalumab for the treatment of advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck cancer. Preclinical data suggested that the combination of these two products will enhance overall anti-tumour response. The US FDA will notify Advaxis within 30 calendar days of any questions relates to the trial protocol. The two companies entered into a collaboration in July 2014 to conduct the trial^[172]^[37].

In November 2018, University of Colorado, Denver and AstraZeneca initiated a phase I/Ib safety trial to assess the safety and efficacy of radiotherapy in combination with durvalumab in patients with non-metastatic, biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, and must be eligible and amenable to surgical resection (18-0606cc; NCT03635164). The open-label, single-group trial is recruiting 60 patients in the US^[252].

In November 2021, AstraZeneca withdrew prior to enrollment the phase I OBERON trial that was designed to evaluate the safety and tolerability of durvalumab and tremelimumab [see Adis Insight drug profile 800020650] in combination with cetuximab [see Adis Insight drug profile 800004458] in patients with recurrent metastatic head and neck squamous cell carcinoma (39187; EudraCT2017-003589-28; ISRCTN89314418). The non-randomised trial was designed to enrol approximately 36 patients in the UK ^[253].

In August 2018, AstraZeneca initiated a phase I trial of durvalumab and tremelimumab [see Adis Insight drug profile 800020650] with radiotherapy for the adjuvant treatment of intermediate risk head and neck squamous cell carcinoma (LCCC 1725; NCT03529422). The open, prospective trial will enrol approximately 24 patients in the US^[254].

In September 2017, MedImmune completed the randomised, open-label, phase I trial that evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of tremelimumab [see AdisInsight drug profile 800020650] alone or in combination with durvalumab, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (D4190C00011; NCT02262741). The dose-exploration and dose-expansion trial was initiated in October 2014 and enrolled 71 patients in Canada and the US^[255].

In December 2017, University Health Network, Toronto, AstraZeneca and Mirati Therapeutics withdrew a phase I trial due to a change in internal prioritisation and not due to any safety concerns, that was designed to evaluate the pharmacodynamics and immune effects of pre-operative therapy with mocetinostat [see AdisInsight drug profile 800020983] and durvalumab on patients with squamous cell carcinoma of the oral cavity (floor of mouth, anterior 2/3 tongue, buccal mucosa, upper and lower gingiva, and retromolar trigone) considered resectable by the head and neck surgical rounds (PRIMED-001; NCT02993991). The non-randomised, open-label, single-group trial intended to enrol 12 patients in Canada^[256].

Glioblastoma

In June 2020, Northwestern University in collaboration with AstraZeneca, Medimmune and National Cancer Institute completed a phase II study comparing tremelimumab and durvalumab monotherapy versus combination therapy administering both drugs, in patients with malignant glioma or recurrent glioblastoma (NU-15C03; STU00202283; P30CA060553; NCI-2016-00665; NCT02794883). The study evaluated changes to T-cells in the blood, before, during and after treatment in all the three arms, as a primary outcome measure. The randomised, open-label study was initiated in September 2016 and enrolled 36 patients in the US^[257].

In July 2021, Ludwig Institute for Cancer Research and Medimmune completed a phase II trial that evaluated the clinical efficacy and safety of durvalumab in patients with glioblastoma (LUD2013-006; NCT02336165).This non-randomised, open-label trial was initiated in February 2015 and enrolled 159 patients in the US and Australia^[258]. Enrolment was completed in February 2017. In June 2019, updated efficacy and safety data from the trial were presented at the 55^rd Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[259]^[260].

In July 2020, Institut Claudius Regaud and AstraZeneca reinitiated the phase I/II STERIMGLI trial in glioblastoma. In August 2019, patient enrolment in the trial was suspended due to an interim analysis. The trial is designed to evaluate the safety and efficacy of durvalumab plus hypofractionated stereotactic radiation therapy, versus radiation therapy alone, in patients with recurrent glioblastoma (NCT02866747; EudraCT2016-001614-16; 16TETE04). The trial was initiated in January 2017 and intends to enrol approximately 112 patients in France^[261].
l
Hepatocellular carcinoma: As of June 2023, AstraZeneca announced that the US FDA approved the tremelimumab (IMJUDO^®) in combination with durvalumab (IMFINZI^®) in the US for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC). The approval was based on positive results from the phase III HIMALAYA trial [see below]^[262]

In February 2023, AstraZeneca announced that EMA approved the tremelimumab (IMJUDO^®) in combination with durvalumab (IMFINZI^®) in the EU for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC). The approval was based on positive results from the phase III HIMALAYA trial [see below]^[263].

In December 2022, durvalumab in combination with tremelimumab [see Adis Insight drug profile 800020650] with chemotherapy was approved in Japan for the treatment of unresectable hepatocellular carcinoma. The approval is based on the phase III HIMALAYA trial [see below]. The same trial also served as a base for an approval of durvalumab monotherapy for the treatment of unresectable hepatocellular carcinoma^[108].

In October 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval of durvalumab as monotherapy for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC)^[264]^[265].

In January 2020, durvalumab was granted orphan drug designation for the treatment of hepatocellular carcinoma (HCC) by the US FDA^[266].

In June 2023, AstraZeneca initiated a phase III SIERRA trial to evaluate the safety and efficacy of Single tremelimumab regular interval durvalumab (STRIDE) as first-line therapy in participants with advanced unresectable hepatocellular carcinoma (NCT05883644; D419CR00030). The open-label, single arm, multicenter trial intends to enrol approximately 140 patients in South Korea and may extend in France, Germany, Hong Kong, Italy, Japan, Singapore, Spain, USA, Vietnam^[267].

In November 2020, National Taiwan University Hospital in collaboration with Ministry of Science and Technology and AstraZeneca initiated a phase II trial to evaluate efficacy of durvalumab in patients with advanced hepatocellular carcinoma with chronic hepatitis B virus infection (NCT04294498; 201910075MIPD). The randomised, open label trial intends to enroll 43 patients in Taiwan^[268]

In February 2023, AstraZeneca initiated phase IIIb TREMENDOUS trial of Durvalumab in combination with Tremelimumab [see adisInsight profile 800020650] in patients with unresectable hepatocellular carcinoma (NCT05557838; D419CR00026). The Non-randomised, open label trial intends to enrol 300 participants in China^[269]

In April 2019, AstraZeneca initiated the phase III EMERALD-2 trial to evaluate the efficacy and safety of durvalumab alone or in combination with bevacizumab [see Adis Insight Drug Profile800008086] in patients with hepatocellular carcinoma who are at high risk of recurrence (NCT03847428; EudraCT2018-004105-85; D910DC00001). Recurrence free survival is the primary endpoint of the trial. The randomized, double-blind, placebo controlled trial will enroll approximately 888 patients in South Korea and may expand to Australia, Canada, China, Germany, Hong Kong, Italy, Japan, Peru, Taiwan, Thailand, Turkey and the US^[270].

In October 2017, AstraZeneca initiated the phase III HIMALAYA trial to evaluate the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable hepatocellular carcinoma (D419CC00002; NCT03298451; EudraCT2016-005126-11; JapicCTI183849; CTRI2018-01-011353). The randomised, open-label study plans to enrol 1324 patients in the US, Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Japan, South Korea, Russia, Spain, Taiwan, Ukraine, Thailand and Vietnam^[271]^[272]. In January 2021, results from the trial were released by the company^[273]. In April 2022, AstraZeneca initiated Himalaya early access programme (EAP) for eligible patients with unresectable, hepatocellular carcinoma (HCC) (NCT05345678; D419CR00019). The study intends to provide early access to tremelimumab 300 mg IV administered once on Day 1 of Cycle 1 plus durvalumab 1500 mg IV followed by durvalumab 1500 mg IV Q4W monotherapy in patients. The number of patients to be enroled will be based on approval of unsolicited requests received from the treating physician^[274]. In July 2022, AstraZeneca released data from the trial and announced that the trial met its primary endpoint demonstrating a statistically significant improvement of OS with a single priming dose of tremelimumab plus durvalumab every four weeks versus sorafenib^[114]. In June 2022, data from the trial was presented at 58th Annual Meeting of the American Society of Clinical Oncology(ASC0-2022)^[275]. In September 2022, results from this trial were released by AstraZeneca^[116]. In November 2022, results from this trial were presented at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD-2022) ^[276]. In July 2023, updated efficacy and adverse events data from a four year follow-up analysis was released by AstraZeneca^[277].

In February 2024, AstraZeneca initiated the phase II EMERALD-Y90 trial to efficacy and safety of durvalumab in combination with bevacizumab [see AdisInsight drug profile800008086] after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in patients with unresectable hepatocellular carcinoma (HCC) amenable to embolization (NCT06040099; D933GC00002). The open label, single group assignment trial intends to enroll 100 patients in the US^[278].

As of July 2023, AVEO Pharmaceuticals terminated the phase Ib/II in patients with hepatocellular carcinoma due to regulatory approval of newer therapeutic options and slower than anticipated accrual. In August 2019, AVEO Oncology and AstraZeneca initiated a phase Ib/II trial to evaluate the safety, tolerability, dose limiting toxicity, maximum tolerated dose and preliminary anti tumour activity of tivozanib [see Adis Insight Drug Profile 800019266] in combination with durvalumab in patients with hepatocellular carcinoma who have not received prior systemic therapy (AV951-18-121; NCT03970616). The phase Ib portion is designed to evaluate the safety, tolerability, dose limiting toxicity, maximum tolerated dose and preliminary anti-tumor activity starting with 1mg of tivozanib for 21 days followed by 7 days rest together with 1500mg of durvalumab every 28 days. Following satisfactory completion of the phase Ib portion of the study, a phase II expansion cohort will enroll at the dose schedule designated in phase Ib. The open-label trial intends to enrol approximately 50 patients. In September 2019, AVEO Oncology announced initiation of patient enrolment in the trial. In January 2021, AVEO Oncology released results from the phase Ib portion of the phase Ib/II DEDUCTIVE trial and announced that phase II portion was ongoing^[279]^[280]^[281].

In April 2019, AstraZeneca initiated a phase II trial to evaluate the safety and efficacy of immunotherapy durvalumab and tremelimumab combined with DEB-TACE in patients with liver cancer (J18118; IRB00179347; NCT03638141). The open label, non-randomised trial intends to enrol 30 patients in the US^[282].

In November 2023, AstraZeneca announced that the phase III EMERALD-1 trial reached its primary end-point for progression-free survival in liver cancer eligible for embolization. In November 2018, AstraZeneca initiated the phase III EMERALD-1 trial to evaluate the efficacy and safety of transarterial chemoembolization (TACE) treatment in combination with durvalumab monotherapy or TACE given with durvalumab plus bevacizumab [see Adis Insight Drug Profile800008086] therapy compared to TACE therapy alone in patients with locoregional hepatocellular carcinoma not amenable to curative therapy (D933GC00001; EudraCT2018-002134-20; NCT03778957). Evaluation of free survival is the primary endpoint of the trial. The randomized, double-blind, placebo controlled trial will enroll approximately 616 patients in the US, Australia, Brazil, Canada, China, France, Hong Kong, India, Italy, Japan, South Korea, Mexico, Spain, Taiwan, Thailand and Vietnam^[283]. In November 2023, data from the phase III trial was released by the company showing positive results^[284]. In January 2024, the Company presented updated adverse events and safety results of the study at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GCS-2024)^[285]^[286].

MedImmune, in October 2015, initiated a phase II trial to evaluate the safety, pharmacodynamics, pharmacokinetics, antitumour activity, and immunogenicity of durvalumab, in combination with tremelimumab [see AdisInsight drug profile 800020650], and both the drugs as a monotherapy, in patients with unresectable hepatocellular carcinoma (D4190C00022; NCT02519348; EudraCT2015-001663-39). The randomised, open-label trial is designed to enrol approximately 144 patients in the US, Hong Kong, Italy, Japan, Singapore, South Korea, Spain and Taiwan. In May 2020, results from the trial were presented at the 56^thAnnual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[287]. Later, in June updated data from the study was released by AstraZeneca in June 2020^[288]^[289].In June 2021, results from the trial were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[290]

In May 2018, Massachusetts General Hospital and AstraZeneca initiated a phase II trial to evaluate the efficacy of durvalumab and tremelimumab [see ADIS insight drug profile800020650] and radiation therapy, in patients with hepatocellular carcinoma and biliary tract cancer (17-517; NCT03482102). Evaluations of the overall response rate is the defined primary endpoint of the trial. The open label trial intends to enrol approximately 70 patients in the US^[291].

In December 2022, AstraZeneca and University College Dublin completed the phase II HCC-TACE study that evaluated the combined immune checkpoint inhibition in combination with ablative therapies in patients with advanced hepatocellular carcinoma (HCC) (EudraCT2019-002767-98; UCDCRC/19/01). The open-label, single-arm study was initiated in May 2020 and enrolled 13 patients in Ireland. The primary objective of the trial to evaluate the 6-month progression free survival (PFS) of combining tremelimumab [see ADIS insight drug profile800020650] and durvalumab in patients with advanced HCC (in combination with TACE). The secondary objectives of the trial is to assess the safety of combining single-dose tremelimumab [see ADIS insight drug profile800020650] and durvalumab in patients with advanced HCC (treated with TACE), and to evaluate changes in immune parameters as well as pharmacokinetics in the peripheral blood of patients with advanced HCC undergoing TACE in combination with combined immune checkpoint inhibition ^[292].

In December 2022, National Cancer Institute completed a phase II trial that evaluated the efficacy of tremelimumab [see AdisInsight drug profile 800020650], in combination with durvalumab, in patients with hepatocellular carcinoma or biliary tract carcinomas (BTC) (160135; 16-C-0135; NCT02821754). The non-randomised, open-label trial was initiated in July 2016, and enrolled 54 patients in the US. In May 2020, the company presented pooled results from this and other trial [see below] at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[293]^[294]. In June 2023, data from the trial was presented at 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) ^[295].

In March 2022, AstraZeneca initiated a phase Ib DEPARTURE trial to evaluate the safety and efficacy of combination therapy of durvalumab/tremelimumab and heavy ion radiotherapy for patients with advanced hepatocellular carcinoma with vascular invasion who are ineligible for standard systemic therapy and Child–Pugh A liver disease (jRCT2031210046). This multi-center, open-label, single-arm, investigator-initiated clinical trial intends to enroll 15 participants in Japan. In January 2024, efficacy and adverse events datafrom phase Ib trial in liver cancer were presented at 2024 Gastrointestinal Cancers Symposium (ASCO-GCS-2024 2024)^[296]^[297]

In April 2023, AstraZeneca and Dana-Farber Cancer Institute initiated a phase I trial to evaluate the safety and tolerability of tremelimumab and durvalumab with or without Selective Internal Yttrium-90 Radioembolization (SIRT) in participants with resectable hepatocellular carcinoma (HCC) who will undergo liver surgery (NCT05701488; 22-401). This open label trial intends to enrol 20 participants in the US^[298]

Malignant melanoma

In March 2022, AstraZeneca initiated the phase II MONETTE trial to evaluate the efficacy and safety/tolerability of ceralasertib [see Adis Insight Drug Profile800039325], when administered as monotherapy and in combination with durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to PD-(L)1 inhibition (NCT05061134; EudraCT2021-001722-21; D533AC00001). The multicentre, open, parallel, prospective, randomised trial intends to enrol approximately 50 patients in Germany, Italy, Spain, and may expand later to USA, Australia, Belgium, Canada, France, South Korea, Poland, and the UK^[299].

In April 2018, MedImmune completed a phase I/II trial that evaluated the safety, tolerability, pharmacokinetics and anti-tumour activity of durvalumab in combination with dabrafenib and/or trametinib [see AdisInsight drug profiles 800030525, 800024261] in patients with metastatic or unresectable melanoma (CD-ON-MEDI4736-1161; NCT02027961). Evaluation of the effect of cmaximum tolerated dose was the primary endpoint of the trial. The open label trial was initiated in December 2013, and enrolled 68 patients in the US, Canada, France, Italy. Preliminary results were presented in May 2015^[300]^[301]^[302].

In June 2023, MedImmune, in collaboration with Immunocore, completed a phase Ib/II study of IMC gp100 [see AdisInsight drug profile 800033036] in combination with durvalumab and/or tremelimumab [see AdisInsight drug profile 800020650], for the potential treatment of metastatic melanoma (IMCgp100-201; NCT02535078). The randomised, open-labelled trial was initiated in November 2015 and enrolled 113 patients in the US^[35]^[303].

Multiple myeloma

In December 2017, Celgene completed the phase II FUSION-MM-005 trial that evaluated the safety and efficacy of durvalumab in combination with daratumumab [see AdisInsight drug profile 800022454], in patients with refractory multiple myeloma (MEDI4736-MM-005; NCT03000452). Evaluation of the objective response was the primary endpoint of the trial. The open-label, single-group trial was initiated in February 2017, and enrolled 18 patients in the US, Austria, Greece, the Netherlands, Spain, Sweden, Germany, and Italy^[47]^[304]. In September 2017, the US FDA placed a partial clinical hold on the trial. The hold was based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48].

In February 2023, Celgene terminated the phase II FUSIONMM-003 trial due to health authority request due to class effect. In January 2022, Celgene completed the phase II trial that evaluated the safety and efficacy of of durvalumab given in combination with daratumumab [see AdisInsight drug profile 800022454], in patients with multiple myeloma (MEDI4736-MM-003; NCT02807454; EudraCT2016-001209-17). The randomised, open-label trial initiated in July 2016, enrolled 37 patients in the US, the UK, Canada, Germany, Italy, Spain, Belgium, Sweden and Denmark. In September 2017, the US FDA placed a partial clinical hold on the phase II FUSIONMM-003 trial. The hold was based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48]^[47]^[305].

In September 2022, Celgene completed a phase I/II trial that determined the recommended dose and regimen of durvalumab 1500mg IV in combination with lenalidomide (25 mg/day or 10 mg/day) [see AdisInsight drug profile 800012854] with or without dexamethasone (40 mg/day or 20 mg/day) in patients with newly diagnosed multiple myeloma (MEDI4736-MM-002; NCT02685826; EudraCT2015-004831-11). Earlier, in September 2017, the US FDA had placed full clinical hold on a phase Ib trial based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48]. The randomised, open-label trial initiated in April 2016 and enrolled 56 patients in Spain, Finland, the US, Canada, Denmark, Italy, the Netherlands, and Germany^[47]^[306].

In September 2017, the US FDA placed a partial clinical hold on a phase Ib trial which was investigating the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide with or without low dose-dexamethasone in patients with relapsed and refractory multiple myeloma (NCT02616640; MEDI4736-MM-001). The hold was based on the risks identified in other trials for an anti-PD-1 agent, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents^[48]. The open-label, randomised trial initiated in January 2016 intended to enrol approximately 121 patients in the Netherlands, the US, Canada, France, Germany, Italy and Spain^[47]^[50]^[307].

In May 2018, MedImmune and Ludwig Institute for Cancer Research terminated a phase I trial as FDA placed on partial hold due to additional data, that was designed to assess the safety and efficacy of tremelimumab and durvalumab combination therapy in patients with multiple myeloma (LUD2014-010; NCT02716805). Checkpoint therapy was to be administered prior to and for two cycles post autologous stem cell transplant. The open-label, parallel, non-randomised trial intended to enrol approximately 24 patients in the US^[308].

In June 2018, Celgene withdrawn a phase II trial prior to enrolment due to safety concerns (373200; U1111-1198-3556; ACTRN12617000958381). The trial was designed to evaluate efficacy of durvalumab rescue for inadequate response to lenalidomide and dexamethasone, in transplant ineligible patients with newly diagnosed multiple myeloma. The open label trial intended to enrol 137 patients in Australia^[309].

Mesothelioma:

In February 2021, AstraZeneca and PrECOG initiated the phase III DREAM3R trial to assess the safety and efficacy of durvalumab in combination with standard chemotherapy of pemetrexed and cisplatin as first-line treatment for patients with unresectable malignant pleural mesothelioma (PrE0506; ALTG 18/001; CTC 0231; NCT04334759; NCT04181411; X19-0462and2019ETH13618; CTC0231PrE0506; CTC0231ALTG18/001PrE0506; ACTRN12620001199909; 380505). The open-label, randomised trial will recruit approximately 480 patients in Australia^[310].

In April 2017, Dana-Farber Cancer Institute and AstraZeneca initiated a phase II trial to evaluate the efficacy of durvalumab in combination with tremelimumab [see AdisInsight drug profile 800020650] for the treatment of patients with malignant pleural mesothelioma (16-549; NCT03075527). This trial is enrolling 40 patients in the US^[311].

In September 2019, AstraZeneca completed a phase I/II DREAM trial that assessed the efficacy of durvalumab combined with cisplatin and pemetrexed as first line therapy in malignant pleural mesothelioma (370989; CTC0142ALTG15/003; X16-0234and-HREC16RPAH287; ACTRN12616001170415). The non-randomized trial was initiated in December 2016 and enrolled 54 patients in Australia. In June 2018, interim efficacy and safety data were presented at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[312]^[313].

In October 2015, AstraZeneca in collaboration with Italian Network for Tumor Biotherapy Foundation initiated the phase II NIBIT-MESO 1 trial to evaluate the efficacy of tremelimumab in combination with durvalumab in patients with unresectable malignant mesothelioma (NCT02588131; NIBIT-MESO-1). The open-label, single-arm trial is recruiting 40 patients in Italy^[314].

In June 2023, AstraZeneca and PrECOG completed a phase II trial that assessed the safety and efficacy of durvalumab in combination with standard chemotherapy of pemetrexed and cisplatin as first-line treatment for patients with unresectable malignant pleural mesothelioma (PrE0505; ESR-15-10792; NCT02899195). The open-label, non-randomised, parallel trial was initiated in May 2017 and enrolled 55 patients in the US^[315]. In May 2020, efficacy and adverse event data from the trial were presented at 56^thAmerican Society of Clinical Oncology (ASCO-2020)^[316].

Baylor College of Medicine initiated a phase I trial in May 2016, to determine whether MEDI 4736 or combination therapy with MEDI 4736 + tremelimumab [see AdisInsight drug profile 800020650] are associated with favourable alterations of the intratumoural immunologic environment in patients undergoing resectional surgery for malignant pleural mesothelioma (MPM) (H-36952; NCT02592551). The open-label, randomised, parallel trial will recruit approximately 20 patients in the US^[317].

Myelodysplastic syndromes

Celgene completed the phase II FUSION HR MDS/ELDERLY AML 001 in December 2021 which evaluated the safety and efficacy of azacitidine in combination with subcutaneous durvalumab, in patients with acute myeloid leukaemia and those who are at a high risk myelodysplastic syndrome (MEDI4736-MDS-001; NCT02775903; EudraCT2015-003596-30). The randomised, open-labelled trial was initiated in June 2016 and enrolled 213 patients in Austria, Portugal, Poland, the Netherlands, Italy, France, Canada, Belgium, USA, Germany, Spain and the UK. The primary endpoint was overall response rate in both myelodysplastic syndrome and acute myeloid leukaemia cohorts. In December 2019, efficacy and safety data from the trial was presented at the 61^stAnnual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2019)^[101]^[50]^[102].

In June 2015, Celgene initiated a phase II trial to evaluate the safety and efficacy of oral azacitidine both alone and in combination with durvalumab for the treatment of myelodysplastic syndromes in patients who failed to reach objective response when treated with azacitidine or decitabine (CC-486-MDS-006; EudraCT2014-002675-29; NCT02281084). The randomised, open-labelled study intends to enrol approximately 194 patients in the US, Australia, Belgium, France, Germany, Poland, Spain and the UK^[50]^[318].

In April 2019, MedImmune completed a phase I trial in that assessed the safety and tolerability of durvalumab as monotherapy, or in combination with tremelimumab [see AdisInsight drug profile800020650] with or without azacitidine, in patients with myelodysplastic syndromes, after treatment with hypomethylating agents (D4190C00007; NCT02117219). The open-label, non-randomised, dose-escalation and dose-expansion study was initiated in May 2014, and enrolled 67 patients in the US, France, Germany and the UK^[319].

Myelofibrosis

In August 2019, Celgene, in collaboration with Northwestern University (sponsor), The Leukemia and Lymphoma Society and National Cancer Institute withdrew a pilot phase I trial prior to enrolment (STU00202833; NU 16H05; P30CA060553; NCI-2016-01024; NCT02871323). The trial was designed to assess the safety and efficacy of durvalumab in patients with myelofibrosis, in the US^[320].

Small cell lung cancer (SCLC)

In August 2020, the Pharmaceuticals and Medical Devices Agency approved durvalumab (120 mg and 500 mg injection) for the treatment of extensive-stage small cell lung cancer^[321].

In November 2021, AstraZeneca initiated the phase IIIb LUMINANCE trial to evaluate the safety and tolerability of durvalumab in combination with cisplatin or carboplatin plus etoposide (EP) as first-line treatment in patients with extensive-stage small-cell lung cancer (NCT04774380; D419QC00007; EudraCT2020-005537-32). The open-label, single-arm, multi-center, international study will enrol approximately 150 patients Czech Republic, Italy, Bulgaria, Germany and may expand to other countries^[322].

In June 2023, AstraZeneca completed phase IIIB trial of durvalumab in combination with platinum-etoposide for untreated patients with extensive-stage small cell lung cancer reflecting real world clinical practice in Spain (CANTABRICO) (NCT04712903; EudraCT2020-002328-35; D419QC00005). The open label trial was initiated in December 2022 enrolled 101 participants in Spain^[323]. In September 2022, efficacy and adverse events data from the trial were presented at the 47^th Congress of the European Society for Medical Oncology (ESMO-2022)^[324].

In June 2023, AstraZeneca initiated the phase II MOZART trial to evaluate the safety and efficacy of the monalizumab [see Adis Insight drug profile800034739] in combination with durvalumab plus platinum-based chemotherapy as first-line treatment in patients with extensive stage small cell lung cancer (NCT05903092; HCRN LUN21-530). The open label trial intends to enrol 38 patients in the US^[29]^[30]^[31]^[325].

In October 2022, AstraZeneca initiated a phase II Aphrodite trial to study the efficacy and safety of combination therapy of durvalumab (MEDI4736) and amrubicin in patients with recurrent small cell lung cancer (jRCT2061220036). This multicenter, open label trial intends to enrol 18 participants in Japan. In October 2022, the company began the enrollment and is expected to complete in March 2025^[326]^[327]

In February 2021, AstraZeneca initiated the phase II TAZMAN trial to assess the efficacy, safety and tolerability of a combination of durvalumab and AZD 2811 [see AdisInsight Drug profile 800037955] as a maintenance therapy, following induction with platinum-based chemotherapy combined with durvalumab, for the first line treatment of advanced small-cell lung cancer. The open label trial has initiated enrolment in the US and South Korea, and intends to expand to Italy and Spain, to enrol a total of approximately 100 patients^[328].

In March 2022, Washington University School of Medicine in collaboration with AstraZeneca initiated a phase II trial to evaluate the safety, tolerability and efficacy of neoantigen DNA vaccine [see ADIS insight drug profile 800049779] in combination with durvalumab+carboplatin+etoposide, in patients with extensive-stage small cell lung cancer (202104143; NCT04397003). The open label trial intends to enrol approximately 27 patients in the US^[329].

Non-small cell lung cancer (NSCLC)

In February 2023, AstraZeneca received approval from the EMA for tremelimumab in combination with durvalumab [see AdisInsight drug profile 800037095] in EU for the treatment of patients with stage IV (metastatic) non-small cell lung cancer (NSCLC). Approval was based on POSEIDON Phase III trial results, which showed significant survival benefit with a limited course of durvalumab added to tremelimumab and chemotherapy^[263].

In December 2022, durvalumab was approved in Japan for the treatment of unresectable, advanced or recurrent NSCLC in combination with tremelimumab [see Adis Insight drug profile 800020650]. The approval is based on the results from the phase III POSEIDON trial [see below]^[108].

As of August 2022, Durvalumab (Imfinzi^®) is available in Netherlands for treatment of patients with NSCLC.

In December 2019, China’s National Medical Products Administration (NMPA) granted marketing authorisation for durvalumab (Imfinzi^®) for the treatment of unresectable, stage III NSCLC, whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. The approval was based on the phase III PACIFIC trial ^[330]^[331].

In July 2018, Japan Ministry of Health approved durvalumab (Imfinzi^®) as a maintenance therapy after definative chemoradiation therapy in locally advanced (stage III), unresectable non-small cell lung cancer (NSCL). The approval is based on positive data from the phase III PACIFIC trial^[332]^[333].

In February 2018, AstraZeneca and MedImmune announced that the US FDA approved durvalumab (Imfinzi^®) for the treatment of patients with unresectable Stage III non-small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy^[334]^[335]. The companies had, in October 2017, announced that the agency accepted their supplemental Biologics License Application (sBLA) and granted priority review status for durvalumab for the treatment of patients with locally advanced, unresectable NSCLC. The sBLA submission was based on positive progression-free survival data from the phase III PACIFIC trial^[336].

In May 2018, the Health Canada approved durvalumab for the treatment of patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy. The drug, reviewed under an accelerated approval, was granted Notice of Compliance with Conditions (NOC/c) based on data from the phase III PACIFIC trial^[337].

In September 2018, AstraZeneca announced that the Brazil Health Regulatory Agency has approved durvalumab for the treatment of locally-advanced, unresectable NSCLC, who had not progressed after standard platinum-based chemotherapy concurrent with radiation therapy. In February 2018, AstraZeneca had reported that the Brazil Health Regulatory Agency granted expedited review to durvalumab. The submission was based on PACIFIC trial data^[338]^[76].

In February 2018, AstraZeneca reported that the the Republic of Korea Ministry of Food and Drug Safety accepted the marketing authorisation application for durvalumab for the treatment of locally-advanced, unresectable NSCLC, who had not progressed after standard platinum-based chemotherapy concurrent with radiation therapy. The submission was based on PACIFIC trial data^[76].

In September 2018, the European Commission granted a marketing authorisation of durvalumab for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥1% of tumour cells and whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT)^[338]. In July 2018, Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency had adopted a positive opinion, recommending a marketing authorisation of durvalumab for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥1% of tumour cells and whose disease was not progressed following platinum-based chemotherapy and radiation therapy (CRT). The recommendation was based on the progression-free survival (PFS) and overall survival (OS) primary endpoints of the Phase III PACIFIC trial, and post-hoc subgroup analyses by PD-L1 expression requested by the CHMP^[339]. In October 2017, AstraZeneca and MedImmune announced that the European Medicines Agency (EMA) accepted a Marketing Authorisation Application (MAA) for durvalumab for the treatment of patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy. The regulatory submission was based on data from the phase III PACIFIC trial^[333]^[340].

In May 2022, the National Institute for Health and Care Excellence (NICE) has published a draft final appraisal document (FAD) recommending durvalumab (Imfinzi) as an option for treating non-small-cell lung cancer (NSCLC) in adults^[341]. Earlier in March 2019, the National Institute for Health and Care Excellence (NICE) published draft final guidance recommending durvalumab that will be available on the National Health Service (NHS) through Cancer Drugs Fund in the UK (England) for the patients with locally advanced unresectable non-small-cell lung cancer, who have already had platinum-based chemoradiation^[342].

In September 2017, the NCCN Clinical Practice Guidelines in Oncology were updated to include durvalumab for the treatment of patients with locally advanced, unresectable NSCLC with no disease progression after two or more cycles of definitive chemoradiation, based on the data from the phase III PACIFIC trial^[336].

In July 2017, the US FDA granted Breakthrough Therapy Designation for durvalumab (IMFINZI™), for the treatment of patients with locally advanced, unresectable non-small cell lung cancer, whose disease has not progressed following platinum-based chemoradiation therapy, based on the interim results from the phase III PACIFIC trial [see below]^[343].

In May 2015, the US FDA granted durvalumab fast track designation for the treatment of advanced NSCLC that has failed two prior systemic-treatment regimens and is EFGR and ALK negative and PD-L1 positive^[344].

In January 2024, AstraZeneca initiated the phase III TRITON trial to assess the efficacy of durvalumab plus tremelimumab [see ADISInsight profile 800020650] in combination with chemotherapy compared with pembrolizumab in combination with chemotherapy in metastatic NSCLC patients with non-squamous histology who have mutations and/or co-mutations in STK11, KEAP1, or KRAS (NCT06008093; D419ML00003). The open label trial intends to enrol approximately 280 participants in the US^[345].

In January 2022, AstraZeneca in collaboration with Arcus Biosciences initiated a phase III PACIFIC-8 trial to evaluate domvanalimab in combination with durvalumab [see Adis Insight drug profile800049306] in patients with locally advanced, unresectable non-small cell lung cancer, whose disease has not progressed following definitive platinum based concurrent chemoradiation therapy (D9075C00001; EudraCT2021-004327-32; NCT05211895). The randomised, double blind, placebo controlled trial will enroll approximately 860 patients in the US, Hungary, Taiwan, Turkey, in the UK, South Africa, Malaysia, Japan, India, Hungary, Greece, Belgium, Norway, Germany, Spain and may expand to Chile, Romania and Russia^[346]^[347].

In August 2022, AstraZeneca initiated the phase III trial to assess the efficacy and safety of the combination of ceralasertib [see Adis Insight drug profile 800039325] and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic non-small cell lung cancer (EudraCT2022-000493-26, NCT05450692;D533BC00001). The randomised, open label trial intends to 580 patients in Argentina, Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, Hong Kong, India, Ireland, Italy, Japan, South Korea, Netherlands, Poland, Romania, Serbia, Spain, Taiwan, United Kingdom and US^[348].

In February 2022, AstraZeneca initiated a phase III PACIFIC-9 trial to investigate the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT (NCT05221840; D9078C00001; EudraCT-2021-004346-37). The randomised trial intends to enrol approximately 999 patients in the US and may extends to the UK, Ukraine, Thailand, Taiwan, Spain, South Korea, Peru, Japan, Italy, Colombia, Canada, Australia^[349]. In April 2022, first patient was dosed in the trial^[350].

In November 2020, AstraZeneca initiated a phase III MERMAID-2 trial to evaluate the efficacy and safety of adjuvant durvalumab in patients with completely resected stage II-III with non-small cell lung cancer (NSCLC) who have undergone curative intent therapy (complete resection and/or neoadjuvant and/or adjuvant therapy), and who are MRD+ during a 96-week surveillance period (D910MC00001; EudraCT2020-000612-30; NCT04642469). The double-blind, randomised trial intends to enrol approximately 284 patients in the UK, Greece, and Taiwan, and is expected to expand to Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Peru, Poland, Romania, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, in the United Kingdom, in US, and Vietnam^[351].

In August 2023, AstraZeneca completed a phase III MERMAID-1 trial which evaluated the efficacy and safety of adjuvant durvalumab in patients with completely resected stage II-III with non-small cell lung cancer (NSCLC) who are MRD+ post surgery (EudraCT2020-000556-35; NCT04385368; CTRI2020-09-027739; D910LC00001). The double-blind, randomised trial was initiated in July 2020 and enrolled 89 patients in Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, South Korea, Mexico, the Netherlands, Peru, Poland, Romania, Russia, Singapore, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Vietnam and in the US^[352]

In March 2023, AstraZeneca completed the phase III PACIFIC-6 trial that assessed the safety of durvalumab (1500mg q4w) in patients with unresectable stage III non-small cell lung cancer (NSCLC), who had not progressed following platinum-based sequential chemoradiation therapy (sCRT) (EudraCT2018-002220-16; D4194C00006; NCT03693300). The open-label, non-randomised trial was initiated in April 2019, and enrolled 117 patients in the US, the UK, Spain, Italy, Germany, and France^[353]. In October 2023, AstraZeneca presented efficacy and adverse events data from the trial at the 48^th European Society for Medical Oncology Congress(ESMO-2023)^[354].

In March 2019, AstraZeneca initiated the PACIFIC-4 phase III study to evaluate the efficacy and safety of durvalumab in patients with unresected clinical Stage I/II lymph node negative non-small-cell lung cancer (D9103C00001; EudraCT2018-002572-41; NCT03833154). The randomised study intends to enroll approximately 690 patients. Enrollment is ongoing at the US, Australia, Belgium, Brazil, Canada, China ,France, Germany, Greece, Israel, Italy, Japan, South Korea, Netherlands, Poland, Puerto Rico, Russia, Spain, Turkey and the UK^[355].

In May 2021, AstraZeneca in collaboration with VU University Medical Center initiated the DIRECT phase II/III study to evaluate the effect of neoadjuvant treatment with tremelizumab [see AdisInsight drug profile 800020650] plus durvalumab in combination with radiotherapy in patients with early-stage non-small cell lung cancer (EudraCT2020-004413-13). The open-label study intends to enrol approximately 24 patients in the Netherlands^[356].

In December 2023, AstraZeneca completed the phase II DUART trial that evaluated the clinical activity of durvalumab following radiation therapy in patients with stage III, unresectable non-small cell lung cancer who are ineligible for chemotherapy (NCT04249362; D4194C00009, EudraCT2019-004336-31). The open-label, non-randomized trial was initiated in November 2020, and enrolled approximately 102 participants in the US, the UK, France, Italy, Poland, Russia and Spain^[357]. In October 2023, AstraZeneca presented efficacy and safety data from the trial at the 48th European Society for Medical Oncology Congress (ESMO-2023)^[358].

In March 2024, the phase II SOUND trial was suspended after the sponsor's decision to comprehensively evaluate the risk and benefit of the study. In November 2022, AstraZeneca initiated the phase II SOUND trial to evaluate the efficacy and safety of savolitinib [see ADIS Insight drug profile800035893] combined with durvalumab in Chinese EGFR wild-type locally advanced or metastatic NSCLC patients with MET alteration (NCT05374603; D5083C00002). The open-label trial intends to enroll 60 patients in China^[359].

In June 2022, AstraZeneca in collaboration with Academic Thoracic Oncology Medical Investigators Consortium completed a phase II trial that evaluated the safety and efficacy of durvalumab as first line therapy in advanced non-small cell lung cancer (NSCLC) patients With ECOG performance status of 2 (PS2) (16-054; NCT02879617). The open-label trial initiated in April 2017, enroled 50 patients in USA^[360].

In September 2021, AstraZeneca initiated a phase II BRIDGE trial to evaluate the efficacy and safety of combining immunotherapy with durvalumab in association with standard chemotherapy and subsequently with standard radiotherapy, followed by a treatment of maintenance with only durvalumab (NCT04765709; IRFMN-NSCLC-8187; EudraCT2019-004025-24). The multicentre, open study intends to enrol 65 patients in France, Italy, and Spain^[361].

In April 2022, AstraZeneca initiated a phase II NeoCOAST 2 study to evaluate monalizumab as neoadjuvant and adjuvant treatment in patients with resectable, early-stage (II to IIIA) non-small cell lung cancer (NCT05061550; EudraCT2021-003369-37; D9077C00001). The open-label, randomised study intends to enroll 350 patients in the US, France, Canada, Italy, South Korea, Portugal and Spain and may further extend in Belgium, Hungary, Ireland, Taiwan, Turkey and Russia^[362].

In December 2021, Sheba Medical Center and AstraZeneca, Rambam Health Care Campus with Tel-Aviv Sourasky Medical Center initiated the phase II CORAL-Lung study to evaluate concomitant radiotherapy, tremelimumab [See Adis Insight Drug Profile 800020650] and durvalumab for metastatic or locally advanced NSCLC patients progressing on first-line immunotherapy (ESR-17-13252; NCT05000710). The intends to enroll 29 patients in Israel^[363].

In June 2020, AstraZeneca in collaboration with University of Utah initiated the phase II STAGGER trial to evaluate the safety and efficacy of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer (HCI127115; NCT04163432). The open label trial intends to enrol 84 patients in the US^[364].

In October 2021, Ludwig Institute for Cancer Research in collaboration with Boehringer Ingelheim and MedImmune completed a phase I/II study to evaluate the safety and preliminary efficacy of the addition of CV 9202 [see Adis Insight RDI profile [800038489]] to tremelimumab [see Adis Insight RDI profile [800020650]] or durvalumab plus tremelimumab in patients with non-small cell lung cancer (LUD2014-012-VAC; NCT03164772).The non-randomised study, initiated in December 2017, enrolled 59 patients in the US ^[365]

In June 2022, AstraZeneca completed the phase II SPIRAL-RT trial which was initiated earlier in September 2019, to evaluate the efficacy and safety of durvalmab when administered to patients with stage III NSCLC unsuitable for chemoradiothrapy who did not have progressive disease after radiation monotherapy (JMA-IIA00434; 2019-2480). The open-label trial enrolled 33 patients in Japan^[366].

In November 2019, AstraZeneca initiated the phase II CHESS trial to assess the efficacy of immunotherapy, chemotherapy plus stereotactic radiotherapy to metastases followed by definitive surgery or radiotherapy to the locoregional primary tumour, in patients with histologically-confirmed synchronous oligo-metastatic non-small cell lung cancer (NCT03965468; ETOP 14-18; ESR-17-13224; EudraCT2018-003011-22). The open-label trial intends to enrol approximately 47 patients in Spain and Switzerland and might expand to Netherlands^[367].

In October 2019, AstraZeneca initiated a phase II trial of durvalumab to investigate the efficacy and safety of durvalumab along with concurrent radiation therapy for untreated patients with unresectable advanced non-small cell lung cancer (JapicCTI194840; WJOG11619L). The phase II study enrolled 35 patients in Japan^[368].

In September 2022, AstraZeneca withdrew a phase II trial to evaluate the safety and efficacy of durvalumab in combination with tremelimumab [see AdisInsight Drug profile800020650] after platinum based chemotherapy compared with platinum based chemotherapy alone as though the study was setup in 2017 and the protocol was adjusted, it was not possible to find suitable patients (EudraCT2017-003780-35; NCT05383001; AIO-TRK-0221; ESR-17-12719). The randomised, open-label trial was initiated in April 2019 and withdrawn prior to enrolment in Germany^[369].

In July 2021, AstraZeneca initiated an investigator sponsored phase I/II trial to evaluate the safety and efficacy of consolidative hypofractionated radiation therapy (hfRT) for boosting the residual primary lung cancer with adjuvant durvalumab after definitive chemoradiation therapy for stage III non-small cell lung cancer (NCT04748419; 004-21). The open-label trial intends to enrol 43 participants in the US^[370].

MedImmune, in July 2023, completed the phase II COAST trial of durvalumab alone or in combination with oleclumab [See ADIS Insight Drug Profile 800042969]or monalizumab [See ADIS Insight Drug Profile800034739] in patients with locally advanced, unresectable (stage III) non-small cell lung cancer (D9108C00001; NCT03822351; EudraCT2018-002931-35). The primary end point of the trial is to determine objective response (OR) rate as a measure of antitumor activity of durvalumab alone vs durvalumab in combination with Oleclumab or Monalizumab at 16 weeks after randomisation. The open-label, randomised trial, initiated in December 2018 and enrolled 188 patients in the US, Canada, France, Hong Kong, Italy, Poland, Portugal, Spain and Taiwan^[371]. Later in September 2021, AstraZeneca presented updated efficacy and adverse events data at European Society for Medical Oncology (ESMO) Congress 2021^[372]^[373].

As of May 2023, AstraZeneca discontinued the phase Ib/II MAGELLAN trial that evaluated the efficacy and safety of durvalumab in combination with novel anti-cancer therapy (oleclumab, danvatirsen) with or without chemotherapy in patients with late-stage, metastatic non-small cell lung cancer (NSCLC) (EudraCT2018-001748-74; D933IC00001; NCT03819465). The randomised, open-label trial initiated in January 2019 and enrolled 258 participants in Austria, Poland, the US, South Korea, Belgium, Canada, Russia, Taiwan, spain, and Thailand^[374].

The OCEANS clinical development programme is assessing durvalumab as monotherapy and in combination with tremelimumab, a CTLA-4 monoclonal antibody, in lung cancer^[19].

In February 2022, AstraZeneca withdrew a phase II trial of durvalumab alone or in combination with chemotherapy (carboplatin and pemetrexed) in kras mutation positive and PD-L1 high (≥ 50%) non-small cell lung cancer patients (NCT04470674; HCRN-LUN17-126). The randomised, open label trial was initiated in April 2021, and intended to enrol patients in the US^[375].

In July 2022, AstraZeneca announced that the trial met its primary co-endpoint pathological complete response (pCR)^[111]. Previously, In December 2018, AstraZeneca initiated a phase III AEGEAN trial to evaluate the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of major pathological response (AEGEAN; D9106C00001; NCT03800134). The randomised, double-blind trial intends to enrol approximately 825 patients in Taiwan, US, Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Costa Rica, France, Germany, Hungary, India, Italy, Japan, South Korea, Mexico, Netherlands, Peru, Philippines, Poland, Romania, Russia, Spain, Thailand and in Vietnam^[376]. In June 2022, the company released positive efficacy and safety data of the trial ^[377]. In March 2023, efficacy and adverse events data from the trial was released by AstraZeneca^[378]. In April 2023, Updated efficacy and adverse events data from the trial were released by AstraZeneca^[379]. In September 2023, clinical data was presented at the 24th World Conference on Lung Cancer (WCLC-2023)^[380]

In January 2019, AstraZeneca initiated a phase III trial, to evaluate efficacy of durvalumab along with chemotherapy given prior to surgery in patients with non-small cell lung cancer (EudraCT2018-002997-29). The double-blind, placebo-controlled trial intends to enrol approximately 300 patients in Hungary.

In November 2018, AstraZeneca initiated a phase III PACIFIC-5 trial to assess the safety and efficacy of durvalumab as consolidation therapy in patients with locally advanced unresectable, non-small cell lung cancer, who have not progressed following definitive, platinum-based, chemoradiation therapy (D933YC00001; NCT03706690). The randomised, placebo-controlled trial intends to enrol approximately 360 patients. Enrolment is underway in South Korea, and is expected to expand in China, Philippines, Poland, Russia, Taiwan and Turkey^[381].

As at December 2023, AstraZeneca discontinued the phase III PACIFIC-2 trial of durvalumab given concurrently with platinum-based chemoradiation therapy in patients with locally advanced, unresectable non-small cell lung cancer (AstraZeneca pipeline, February 2024). In November 2023, AstraZeneca announced that the trial did not achieve statistical significance for the primary endpoint. In April 2018, AstraZeneca initiated a phase III study to assess the efficacy and safety of durvalumab given concurrently with platinum-based chemoradiation therapy in patients with locally advanced, unresectable non-small cell lung cancer (D933KC00001; NCT03519971). In fourth quarter of 2019, AstraZeneca completed an enrolment in the trial. The randomised, placebo-controlled, double-blind, multi-centre, international study enrolled 328 patients in Brazil, Hungary, India, Mexico, Philippines, Poland, Thailand, Turkey, Vietnam, Russia, South Korea and Japan, Peru and Czech Republic^[382]^[383]. In November 2023, efficacy and adverse events data from the trial released by the company^[384].

In November 2022, AstraZeneca received approval from the US FDA for tremelimumab [see AdisInsight drug profile 800020650] in combination with durvalumab for the treatment of patients with stage IV (metastatic) non-small cell lung cancer (NSCLC). Approval was based on POSEIDON Phase III trial results, which showed significant survival benefit with a limited course of durvalumab added to tremelimumab and chemotherapy^[385].

In December 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted positive opinion for durvalumab in combination with tremelimumab [see AdisInsight drug profile 800020650] and platinum-based chemotherapy for the first-line treatment of adults with metastatic NSCLC in European Union^[386]^[387].

Before November 2022, AstraZeneca submitted regulatory applications in Japan and several other countries for non-small cell lung cancer based on the POSEIDON results.

In June 2017, AstraZeneca initiated the phase III POSEIDON trial to determine the efficacy and safety of durvalumab + tremelimumab combination therapy + standard of care (SoC) chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as first line treatment in patients with metastatic non-small cell lung cancer with tumours that lack activating EGFR mutations and anaplastic lymphoma kinase ALK fusions (D419MC00004; EudraCT2017-000920-81; NCT03164616; JapicCTI173673). The randomised, open-label trial intends to enrol approximately 1193 patients in Brazil, Bulgaria, China, Germany, Hong Kong, Hungary, Japan, Mexico, Peru, Poland, Russia, South Africa, South Korea, Taiwan, Thailand, Ukraine, United Kingdom, the US and Vietnam^[388]. In October 2019, AstraZeneca completed the recruitment in the study and released results from the trial that showed that the trial met both its primary and secondary end points. In May 2021, AstraZeneca released updated efficacy and adverse events data from the trial. In September 2021, updated efficacy and safety data from the trial were released by the company. In June 2022, results from this trial were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[389]^[390]^[391]^[271]^[392]. In September 2022, AstraZeneca released additional four years follow-up data from the trial, and subsequently presented the data at the European Society of Medical Oncology Congress (ESMO-2022)^[393].

In December 2022, AstraZeneca reported that phase III PEARL trial did not achieve statistical significance for the primary endpoints of improving overall survival (OS) versus platinum-based chemotherapy, or in a subgroup of patients at low risk of early mortality^[394]. In October 2019, AstraZeneca completed recruitment in the phase III PEARL trial that determine the efficacy and safety of durvalumab monotherapy versus platinum-based SoC chemotherapy in the first-line treatment of advanced NSCLC in patients who are epidermal growth factor receptor and anaplastic lymphoma kinase wild-type and with PD-L1-high expression (D419AC00002; NCT030039l62). The randomised, open-label, parallel-group trial was initiated January 2017 and enrolled 671 patients in the US, Hungary, China, South Korea, Thailand, the Netherlands, Poland, Vietnam, Taiwan, Turkey, Australia and Russia^[271]^[395] ^[396].

In July 2017, AstraZeneca reported initial results from the phase III MYSTIC trial demonstrating that the combination treatment of durvalumab and tremelimumab did not meet a primary endpoint of improvement in the progression free survival as compared with standard of care regimen, in patients with 25% or more PDL1 expression on cancer cells (D419AC00001; NCT02453282; EudraCT2015-001279-39). The assessment of other two primary endpoints of overall survival for durvalumab monotherapy and combination therapy with tremelimumab is ongoing. The trial is designed to compare the safety and efficacy of durvalumab as a single agent and in combination with tremelimumab [see AdisInsight drug profile 800020650] versus platinum-based chemotherapy (SoC) as first-line therapy in patients with late-stage or metastatic NSCLC. The trial was initially focused on PFS; however, in January 2017, the company refined endpoints, to include overall survival (OS) as a co-primary endpoint, based on data showing durvalumab’s strong efficacy as a monotherapy. The trial will now assess PFS and OS in patients with PDL1-expressing tumours for both durvalumab monotherapy and combination therapy, and also in ‘all comers’ for the combination therapy, as compared with SoC chemotherapy. The randomised, open-label trial, initiated in July 2015, enrolled 1 118 patients in the US, Australia, Belgium, Canada, France, Germany, Hungary, Italy, Switzerland, Japan, the Netherlands, Russia, Spain, South Korea, Taiwan, Thailand and Vietnam^[397]^[395]^[215]^[301]^[398]. Final results from the trial were released in November 2018^[63]. In December 2018, AstraZeneca and MedImmune presented results for the trial at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-2018)^[399].

AstraZeneca, in November 2015, initiated the NEPTUNE phase III trial to determine the efficacy and safety of durvalumab in combination with tremelimumab versus platinum-based standard of care chemotherapy in the first-line treatment of patients advanced or metastatic NSCLC (D419AC00003; NCT02542293). Enrolment of 960 patients has been completed in South Korea, the US, Argentina, Brazil, Bulgaria, China, Chile, Denmark, Finland, Greece, Hong Kong, India, Israel, Japan, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russia, Saudi Arabia, Singapore, Sweden, Turkey, Ukraine and the UK^[76]^[395]^[400]^[401]. In August 2019, AstraZeneca reported that the trial failed to meet its primary endpoint^[402].

In July 2023, AstraZeneca completed the phase III CAURAL trial which was designed to evaluate the safety and efficacy of osimertinib as single agent and in combination with durvalumab in patients with late-stage, metastatic T790M mutation positive NSCLC who have received prior epidermal growth factor receptor tyrosine kinase inhibitor therapy (D5165C00001; NCT02454933). The trial was reinitiated in March 2016 which was earlier suspended in October 2015. The randomised, open-label trial was initiated in July 2015 and enrolled 29 participants in South Korea, Taiwan and Canada^[403].

AstraZeneca is planning a phase III trial to investigate the combination of durvalumab and gefitinib [see AdisInsight drug profile 800007340] as first line treatment of EGFR mutation NSCLC^[404]^[405].

In August 2023, AstraZeneca completed the randomised, open-label phase III ARCTIC trial, that was designed to investigate the efficacy and safety of durvalumab as monotherapy, or in combination with tremelimumab, in patients with locally advanced or metastatic NSCLC who have received at least two prior lines of therapy (D4191C00004; NCT02352948; EudraCT2014-000338-46). The trial was initiated in January 2015 and enrolled 597 patients in the US, Australia, Belgium, Bulgaria, Canada, Chile, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, South Korea, Netherlands, Poland, Russia, Romania, Serbia, Singapore, Spain, Taiwan, Thailand, and the UK (MedImmune pipeline, June 2018)^[76]^[406]. In April 2018, the company released efficacy data which demonstrated that sub-study B failed to meet the primary endpoint and sub-study A was not powered for statistical significance^[407]. In October 2018, AstraZeneca presented results from the trial at the 43rd European Society for Medical Oncology Congress (ESMO-2018)^[408]^[409].

In May 2017, the interim data from the phase III PACIFIC trial demonstrated that the primary endpoint of statistically-significant and clinically-meaningful progression free survival was met in all-comer patients with locally-advanced, unresectable (Stage III) non-small cell lung cancer and the results demonstrated a favourable benefit/risk profile (D4191C00001; NCT02125461; EudraCT2014-000336-42). In May 2018, durvalumab met the second primary endpoint of statistically-significant overall survival benefit with clinically-meaningful improvement in patients receiving durvalumab compared to placebo, in the planned interim analysis conducted by an Independent Data Monitoring Committee. The safety and tolerability profile for durvalumab was consistent with that reported at the time of the progression-free survival (PFS) analysis^[333]^[410]. In May 2014, AstraZeneca initiated the trial to assess the effects of durvalumab following concurrent chemotherapy in NSCLC patients, whose disease has not progressed following platinum-based chemoradiation therapy. The randomised, double-blind, placebo-controlled trial completed enrolment of 983 patients in the US, Canada, Mexico, Chile, Peru, the UK, Belgium, Germany, Hungary, Italy, Spain, Poland, France, the Netherlands, Slovakia, Greece, Turkey, South Africa, Australia, Japan, South Korea, Singapore, Taiwan, Israel, Thailand and Vietnam. In September 2020, updated results from the trial were presented at the 45^thEuropean Society for Medical Oncology Congress (ESMO-2020). Later, in June 2021, updated data was presented at the 57th American Society of Clinical Oncology Annual Meeting (ASCO-2021)^[411]^[412]^[413]^[414]^[415]^[416]^[417]^[406]^[215]^[418].

In November 2014, NCIC Clinical Trials Group initiated the phase III ADJUVANT trial, to evaluate durvalumab in the adjuvant setting in completely resected NSCLC (BR31; IFCT1401; ACTRN12615000323527; NCT02273375). This double-blind, randomised trial enrolled 13060 patients in the US, Australia, Canada, France, Italy, Japan, South Korea, Netherlands, New Zealand, Singapore, Spain, Taiwan, Bulgaria, Brazil, China, Hungary, Poland, Romania, Ukraine. In fourth quarter of 2019, AstaZeneca completed enrolment in the trial^[382]^[301]^[419]^[420].

In February 2022, the Southwest Oncology Group, in collaboration with the US National Cancer Institute as well as MedImmune, AstraZeneca, Pfizer, Amgen and Genentech, completed the Lung Cancer Master Protocol (Lung-MAP) phase II/III trial in the US, initiated in June 2014 and enrolled 1864 participants(S1400; NCI-2014-00627; S1400E; S1400A; S1400I; S1400C; S1400D; S1400B; U10CA180888; NCT02154490). The trial is investigating biomarker-driven targeted therapy to treat patients with stage IIIB or IV squamous NSCLC who have failed first-line therapy with a platinum-based regimen for metastatic disease. Docetaxel, erlotinib, nivolumab, palbociclib, ipilimumab, durvalumab, rilotumumab [see AdisInsight drug profile 800015060], taselisib [see AdisInsight drug profile 800033797], AZD-4547 [see AdisInsight drug profile 800030912] will be evaluated in the study. Approximately, 10000 patients will be enrolled and assigned to a treatment arm based on the cancer mutation genomic profile. This trial contains multiple sub-studies. In June 2014, National Cancer Institute and Southwest Oncology Group initiated the phase II Lung-Map Sub-Study trial to assess the efficacy of durvalumab in patients with stage IV, recurrent squamous cell lung cancer and no-matching biomarkers (NCI-2014-01378; S1400A; U10CA180888; NCT02766335). The open-label, parallel, non-randomised trial recruited 100 patients in the US ^[421]^[422].

In December 2022, AstraZeneca in collaboration with Radboud University completed a phase II trial that assessed the feasibility and safety of durvalumab in neo-adjuvant setting in patients with resectable NSCLC (ESR17-13332; EudraCT2019-000670-37; NCT03853187; NL68987-091-19). The open-label trial was initiated in September 2019 and enrolled 20 patients in the Netherlands^[423].

In January 2021, MedImmune completed the phase II NeoCOAST trial, which evaluated the safety and efficacy of neoadjuvant durvalumab alone or in combination with oleclumab [see Adis Insight profile 800042969], monalizumab [see Adis Insight profile 800034739] or danvatirsen [see Adis Insight profile 800021483], for the treatment of patients with non-small cell lung cancer (D9108C00002; NCT03794544; EudraCT2018-002932-26). The randomised, open-label study was initiated in March 2019 and enrolled 84 patients in the US, Canada, France, Italy, Portugal, Spain and Switzerland^[424]. In April 2022, efficacy and safety data from the trial were presented at the 113^th Annual Meeting of the American Association for Cancer Research (AACR-2022)^[425]. In September 2022, efficacy data from the trial were presented at the 47^th European Society for Medical Oncology Congress (ESMO-2022)^[426].

Prior to August 2022, AstraZeneca completed the phase II ORION trial which evaluated the efficacy and safety of durvalumab plus olaparib combination therapy, as compared with durvalumab monotherapy as a maintenance therapy, in patients whose disease has not progressed following standard of care (SoC) platinum-based chemotherapy with durvalumab as a first-line treatment in patients with stage IV non small-cell lung cancer (NCT03775486; D9102C00001; EudraCT2018-003460-30). The trial includes patients with tumors lacking activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions. The randomised, double blind trial was initiated in December 2018, and enrolled 401 patients in the US, Belgium, France, Hungary, India, South Korea, Mexico, Netherlands, Poland, Romania, Russia, Ukraine, the UK, and Japan ^[427].

In December 2022, Celgene and AstraZeneca in collaboration with AIO-Studien-gGmbH completed the phase II DURATION trial which evaluated the safety and tolerability of sequential therapy consisting of standard of care mono- or combination chemotherapy followed by durvalumab in comparison to standard of care mono- or combination chemotherapy in frail/elderly patients (NCT03345810; AIO-YMO/TRK-0416; EudraCT 2016-003963-20; ESR-15-11003). The open, parallel, prospective, randomised trial was initiated in December 2017, enroled approximately 200 patients in Germany^[428]. In October 2023, efficacy and safety data were presented at the 48th European Society for Medical Oncology Congress (ESMO-2023)^[429].

In December 2017, AstraZeneca initiated the phase II HUDSON trial to evaluate the efficacy, safety, and tolerability of durvalumab, AZD 6738 [see AdisInsight drug profile 800039325], AZD 9150 [see AdisInsight drug profile 800021483], olaparib [see AdisInsight drug profile 800024096] and vistusertib [see AdisInsight drug profile 800031625] in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy (119833; D6185C00001; NCT03334617). The open, parallel, prospective trial is enrolling approximately 200 patients in Canada, South Korea and may extend to the US, Austria, France, Germany and Israel^[430].

In March 2017, Canadian Cancer Trials Group and AstraZeneca initiated a phase II trial to assess the efficacy of durvalumab, in combination with tremelinumab [see AdisInsight drug profile 800020650] in patients with advanced metastatic NSCLC (NCT03057106; BR34). Overall survival is the defined primary endpoint of the trial. The randomized trial is enrolling 300 patients in Australia and Canada^[431].

In March 2016, The Swiss Group for Clinical Cancer Research initiated a phase II trial to evaluate the efficacy and feasibility of adding neoadjuvant and adjuvant immunotherapy with durvalumab to standard neoadjuvant chemotherapy in primary resectable stage IIIA(N2) NSCLC (NCT02572843; SAKK 16/14; 000001480). The open-label trial completed enrolment of 68 patients in Switzerland, in January 2020^[432]. In September 2020, the company presented safety and efficacy data from the trial at the 45^th European Society for Medical Oncology Congress (ESMO-2020)^[433].

University of Texas M.D. Anderson Cancer Center in collaboration with MedImmune and AstraZeneca planned to initiate a phase II trial to evaluate safety and efficacy of durvalumab in combination with selumetinib in patients with KRAS mutant NSCLC, however the trial was withdrawn prior to enrolment due to insufficient funding (2016-0060; NCT03004105). The randomised, parallel, open-labelled trial was designed to enrol approximately 76 patients in the US^[434].

In September 2016, IFCT initiated a prospective phase II trial of durvalumab, for the treatment of patients with early stage resectable NSCLC (IFCT-1601; EudraCT2016-001849-15). The trial intends to evaluate the impact of neo-adjuvant therapy with durvalumab, for one month on complete resection. The open label trial intends to enrol 81 patients in France^[435].

In October 2015, Peregrine Pharmaceuticals, in collaboration with AstraZeneca, a global phase II trial included durvalumab in combination with bavituximab [see AdisInsight drug profile 800022616] in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC) (NCT02673814). However, as of March 2016, the trial was suspended by the company. The randomised trial to be conducted by Peregrine planned to include approximately 198 patients^[21]^[22].

In June 2016, AstraZeneca completed a randomised, open-label phase IIa trial, which investigated the efficacy of gefitinib, osimertinib, selumetinib plus docetaxel, and tremelimumab, with switch to durvalumab, in patients with locally advanced or metastatic NSCLC (D4191C00011; NCT02179671) [see AdisInsight drug profiles 800007340, 800037784, 800019504, 800020650]. The trial was initiated in July 2014 and enrolment of approximately 40 patients was completed in the US in October 2015^[436].

In February 2014, AstraZeneca initiated a single-arm phase II ATLANTIC trial to evaluate the efficacy and safety of durvalumab in patients with locally advanced or metastatic PD-L1-positive NSCLC who have received at least two prior treatment regimens, including one platinum-based chemotherapy regimen (D4191C00003; NCT02087423; EudraCT2013-005427-16). The primary endpoint will be objective response rate, assessed over 2 years. Enrolment of 453 patients has begun in the US, Austria, Belgium, Canada, the Czech Republic, France, Germany, Hungary, Italy, Japan, South Korea, Philippines, Poland, Singapore, Spain, Taiwan, Thailand and the UK^[437]. In June 2017, MedImmune presented pooled efficacy and safety data of ATLANTIC and 1108 (see below) trial at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO-2017)^[438]^[439].

In October 2022, Weill Medical College of Cornell University and AstraZeneca completed a phase II trial to assess the safety and efficacy of durvalumab with or without stereotactic body radiation therapy (SBRT) in patients with stage I, II and IIIA NSCLC prior to surgery and one year following surgery (1501015795; NCT02904954). The open-label, parallel, randomised trial was initiated in December 2016 and enrolled 60 patients in the US^[440].

In December 2018, MedPacto and AstraZeneca initiated a phase Ib/IIa trial to evaluate the safety and efficacy of vactosertib in combination with durvalumab in patients with metastatic non-small cell lung cancer (NCT03732274; MP-VAC203). The open-label trial is enrolling approximately 63 patients in South Korea^[441].

In February 2018, AstraZeneca initiated a phase Ib/II trial to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD 9150 [see AdisInsight drug profile 800021483] plus durvalumab, alone or in combination with chemotherapy in patients with advanced solid tumours and subsequently in patients with non-small-cell lung cancer (D5660C00016; REFMAL 558; NCT03421353). The randomised, parallel, open-label trial is intended to enrol approximately 213 patients in the US^[442].

In October 2017, Jonsson Comprehensive Cancer Center, AstraZeneca and National Cancer Institute initiated the phase I/II ISABR trial of ablative radiotherapy plus durvalumab for medically inoperable early-stage non-small cell lung cancer (17-000004; NCT03148327). The open, parallel, prospective, randomised trial is enrolling approximately 105 patients in the US^[443].

In August 2017, Ludwig Institute for Cancer Research, MedImmune, Xcovery and Cancer Research Institute, New York completed a phase I/II trial that evaluated the safety and preliminary efficacy of ensartinib [see AdisInsight drug profile 800036425] monotherapy and combination therapy with durvalumab, in patients with with ALK-positive NSCLC (LUD2014-012-ALK; NCT02898116). Evaluation of the treatment emergent adverse events was the primary endpoint of the trial. The open-label, parallel, non-randomised trial was initiated in March 2017, and enrolled two patients in the US^[444].

In June 2020, MedImmune and Mirati Therapeutics terminated a phase I/II trial early because the sponsor de-prioritized development of mocetinostat. The decision to stop was not due to any patient safety issues (0103-020, NCT02805660). The trial was initiated in June 2016 to evaluate the safety and efficacy of durvalumab in combination with the latter's histone deacetylase inhibitor, mocetinostat, in patients with NSCLC and advanced or metastatic solid tumours. The trial enrolled 83 patients in the US^[19]^[445].

In January 2021, AstraZeneca and Daiichi Sankyo initiated the phase Ib DESTINY-Lung03 trial to evaluate the safety, tolerability and preliminary efficacy of trastuzumab deruxtecan and durvalumab in combination with cisplatin, carboplatin or pemetrexed in first-line treatment of patients with advanced or metastatic HER2+ non-squamous non-small cell lung (DL03; D967YC00001; NCT04686305). The open-label dose-escalation Study intends to enrol 120 participants in Taiwan and may expand to the US, Canada, Belgium, Italy, South Korea, Spain and Thailand^[446].

In December 2020, AstraZeneca initiated a phase I trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of durvalumab, in combination with MEDI 9253 [see AdisInsight drug profile 800061111], in patients with select advanced/metastatic solid tumours including stable colorectal cancer (MSS-CRC), renal cell carcinoma (D7880C00001; NCT04613492). The open-label, non-randomised, dose escalation and dose expansion study enrolled 37 patients in the US and France^[447]^[448]. The dose escalation phase will evaluate a single dose of MEDI 9253 with sequential durvalumab, then multiple-dose cohorts of up to 4 ascending dose levels of MEDI9253 with sequential or concurrent durvalumab. The dose expansion phase will include 3 cohorts of ~20 patients, each enrolling a single tumor type^[448]. In March 2023, data from the trial were presented at 21^st International Congress on Targeted Anticancer Therapies (TAT-2023)^[449].

In July 2020, AstraZeneca, in collaboration with University of Wisconsin and National Cancer Institute, due to a slow accrual terminated a phase Ib trial that evaluated the safety and tolerability of durvalumab and tremelimumab [see AdisInsight drug profile 800020650] with stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic NSCLC (NCT03275597; P30CA014520; UW17003; 2017-0665, A533300; NCI2017-01952; Protocol-Version10/2//2020; Protocol-Version1-9-2020; SMPH-HUMAN-ONCOLOGY-HUMAN-ONCO). This open-label trial was initiated in February 2018 and enrolled 31 patients in the US. Later, in June 2021, data were presented at the 57^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[450]^[451].

Positive preclinical data involving the combination therapy of durvalumab and monalizumab [see Adis Insight Drug profile 800034739] were presented at the American Association for Cancer Research Annual Meeting (AACR-2018), in April 2018^[452].

In August 2014, AstraZeneca initiated the phase Ib TATTON trial to determine the safety, tolerability and preliminary anti-tumour activity of mereletinib [see AdisInsight drug profile 800037784] in combination with durvalumab, savolitinib or selumetinib in patients with EGFR mutation positive advanced lung cancer (D5160C00006; NCT02143466). The open-label, non-randomised study is intended to enrol approximately 344 patients in the US, Japan, South Korea, Taiwan, Canada, Poland, Russia and Ukraine^[453]. Preliminary data from the trial indicated that durvalumab and mereletinib were tolerated at their phase III doses in the combination arm^[300]. In April 2021, efficacy data from the trial presented at the 112th Annual Meeting of the American Association for Cancer Research (AACR-2021)^[454].

In March 2021, AstraZeneca in collaboration with MedImmune completed a phase I trial which assessed the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of gefitinib [see RDI profile800007340] in combination with durvalumab in patients with advanced NSCLC in escalation phase and advanced EGFR mutant NSCLC in expansion phase (D791PC00001; NCT02088112). The trial consisted of two parts: part I is an escalation phase conducted in advanced NSCLC patients and part II is an expansion phase conducted in advanced EGFR mutant NSCLC. The open-label trial was initiated in March 2014 and enrolled 56 patients in the US, Japan and South Korea^[455]. Interim data from the trial showed that the combination was generally well tolerated and had early treatment activity in heavily pre-treated patients^[300].

In September 2019, MedImmune completed a phase Ib/II trial that investigated the safety and tolerability of durvalumab, in combination with tremelimumab [see AdisInsight drug profile 800020650], in patients with advanced NSCLC (Study 006; D4190C00006; EudraCT2015-003715-38; NCT02000947). The open-label, dose-escalation trial was initiated in October 2013 and enrolled 459 patients in the US, Australia, Belgium, France, Germany, Italy, South Korea, Spain, Taiwan and the UK^[456]. Positive interim data from the dose-escalation part of the trial have been presented, and identified a range of doses to be used for phase III combination studies. A specific dose and schedule of durvalumab 20mg every four weeks (12 total doses) and tremelimumab 1mg/kg every four weeks (four total doses) were selected^[300]. In February 2016 and April 2018, updated efficacy and safety results of the trial were released by AstraZeneca and MedImmune^[457]^[458].

Non-Hodgkin lymphoma

In February 2023, Juno Therapeutics, in collaboration with Celgene Corporation, completed the exploratory phase I/II PLATFORM trial that evaluated the safety and efficacy of lisocabtagene maraleucel [see AdisInsight drug profile800041076], in combination with avadomide or durvalumab, in patients with relapsed or refractory aggressive non-Hodgkin lymphoma, diffuse large B cell lymphoma and follicular lymphoma (JCAR017-BCM-002; U1111-1201-2046; NCT03310619). The open-label trial was initiated in November 2017, and enrolled 62 patients in the US^[459]^[460].

In May 2021, Fred Hutchinson Cancer Research Center in collaboration with Juno Therapeutics terminated a phase Ib trial due to slow accrual, which was initiated to investigate the safety and efficacy of the combination of durvalumab with JCAR 014 [see AdisInsight drug profile 800041075] for the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (NCT02706405; NCI-2015-02286; 9457; P30CA015704; R01CA136551). The open-label, non-randomised trial was initiated in November 2016 and enrolled 29 patients in the US [700269061]. The IND application for the phase Ib trial was approved by the US FDA in late 2015 [809195683] [809192012]. In December 2022, data from the trial was presented at the 64^th American Society of Hematology Annual Meeting and Exposition (ASH-2022)^[461].

Oesophageal cancer

In October 2020 AstraZeneca initiated a phase III KUNLUN trial to evaluate durvalumab in combination with chemoradiation therapy in patients with advanced, unresectable oesophageal cancer (D910SC00001; NCT04550260). The randomised, double blind, placebo controlled trial will enrol approximately 600 patients in Taiwan and South Korea, and may extend to Brazil, China, Japan and Thailand^[462].

In October 2018, Cambridge University Hospitals NHS Foundation Trust and AstraZeneca initiated a phase II CALIBRATION trial to evaluate whether early changes in circulating tumour DNA can predict tumour response, in patients with advanced oesophageal malignancies receiving durvalumab (NCT03653052). Evaluation of the clinical response to therapy is the defined primary endpoint of the trial. The open label trial intends to enrol approximately 19 patients in the UK^[463]. In September 2020, the company presented updated results of the trial at the 45th European Society for Medical Oncology Congress (ESMO-2020)^[464].

In June 2021, Big Ten Cancer Research Consortium, in collaboration with Medimmune and AstraZeneca, completed a phase II trial that evaluated safety and efficacy of durvalumab following multi-modality therapy in patients with oesophageal cancer (BTCRC-ESO14-012; NCT02639065). In October 2019, the open-label trial was initiated in April 2016 and completed enrolment of 39 patients in the US^[465]. In May 2020, the company presented updated results from this trial at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[466].

In June 2022, The Ludwig Institute for Cancer Research in collaboration with AstraZeneca completed an open-label, phase I/II study that evaluated the safety of durvalumab in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer and with neoadjuvant chemotherapy before surgery in operable oesophageal cancer (NCT02735239; EudraCT2015-005298-19; LUD2015-005). The trial was initiated in June 2016 and enrolled 73 patients in the UK^[467].

In February 2016, Samsung Medical Center initiated a phase II trial to evaluate durvalumab, as an adjuvant therapy, in patients with completely resected oesophageal cancer, previously treated with neoadjuvant concurrent chemoradiotherapy (2015-06-166; NCT02520453). The placebo-controlled, randomised, double-blind study is designed to enrol approximately 84 patients in South Korea^[468].

Oropharyngeal cancer

In February 2023, AstraZeneca in collaboration with Institut Claudius Regaud completed the phase II CITHARE trial which evaluated the efficacy and the safety of definitive Radiotherapy (RT) (70 Gy) delivered in combination with durvalumab immunotherapy in patients with Human Papilloma Virus (HPV)-related oropharyngeal squamous cell carcinoma (18VADS06; NCT03623646). The open-label, randomised trial was initiated in March 2019, enroled 11 patients in France^[469].

In January 2018, AstraZeneca in collaboration with Canadian Cancer Trials Group initiated a phase II study to study cisplatin plus radiotherapy versus durvalumab plus radiotherapy followed by adjuvant durvalumab versus durvalumab plus radiotherapy followed by adjuvant tremelimumab and durvalumab in patients with locoregionally advanced oropharyngeal squamous cell cancer (HN9; NCT03410615). The non-comparative, randomised study intends to enrol approximately 140 patients in Canada^[470].

In March 2021, AstraZeneca in collaboration with M.D. Anderson Cancer Center completed the phase I CIAO trial that evaluated durvalumab alone or in combination with tremelimumab [see AdisInsight drug profile 800020650] to patients with oropharynx carcinoma before standard-of-care surgery can help to control the disease (NCT03144778; 2016-0805). The open, parallel, prospective, randomised trial initiated in July 2017 enrolled 39 patients in the US^[471].

Ovarian cancer

In January 2019, AstraZeneca in collaboration with Myriad Genetic Laboratories initiated a phase III DUO-O trial to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer, primary peritoneal and/or fallopian tube cancer (D081RC00001; EudraCT2017-004632-11; JapicCTI184212; NCT03737643). The randomised, double-blind study intends to enrol 1200 patients in South Korea, Finland, Hungary, Austria, US, Belgium, Japan, Bulgaria, Canada, Denmark, France, Germany, Italy, Romania and Turkey^[472]. In June 2023, the company released the data from the trial^[473]. In June 2023, updated data from the study were presented at the 59^th American Society of Clinical Oncology Annual Meeting (ASCO-2023)^[474]^[475].

In July 2019, Yonsei University and AstraZeneca initiated the phase II TRU-D trial to evaluate the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer (KCT0003742; ESR17-13142; KGOG3046; NCT03899610). The open label trial intends to enrol approximately 24 patients in South Korea^[476]. In April 2022, efficacy and safety data from the trial were presented at the 113^th Annual Meeting of the American Association for Cancer Research (AACR-2022)^[477].

In January 2022, Institut Bergonié, in collaboration with AstraZeneca and PharmaMar completed a TRAMUNE phase Ib trial that investigated the safety and efficacy of trabectedin, in combination with durvalumab, in patients with ovarian cancer and soft tissue sarcoma (NCT03085225; IB2016-02). The open-label trial was initiated in 2017 and enrolled 30 patients in France^[478]. .

M.D. Anderson Cancer Center and AstraZeneca, in May 2017, initiated a phase II trial to evaluate the safety and efficacy of tremelimumab and durvalumab given in combination versus sequentially in patients with high-grade, recurrent, platinum-resistant epithelial ovarian, peritoneal or fallopian tube cancer (2016-0093; NCT03026062). The open-label, randomised, parallel trial intends to enrol approximately 100 patients in the US^[479]. In March 2022, Northwestern University released preliminary data from the trial^[480]

In October 2017, ARCAGY/GINECO-Group and AstraZeneca initiated a phase Ib/II INEOV trial to assess the afety and feasibility in neo-adjuvant first-line ovarian cancer (including patients with primary peritoneal or fallopian tube adenocarcinoma) of various combinations of durvalumab with chemotherapy with or without tremelimumab (GINECO-OV127b; NCT03249142). In February 2021, the randomised, open-label trial completed enrolment of 66 patients in France^[481]. In September 2021, efficacy and safety data from the trial was presented at the 46^th European Society for Medical Oncology Congress (ESMO-2021)^[482]. In June 2022, the company presented the updated results from this trial at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[483].

In June 2021, Ludwig Institute for Cancer Research in collaboration with MedImmune, VentiRx Pharmaceuticals (now Celgene) and Institute of Cancer Research, completed a phase I/II trial which evaluated the safety and efficacy of durvalumab in combination with motolimod [see AdisInsight drug profile 800029322] in patients with recurrent, platinum-resistant ovarian cancer (LUD2014-001; NCT02431559). The trial was initiated in November 2015. The open-label trial is recruiting 53 patients, who are scheduled to receive pegylated liposomal doxorubicin, in the US and Switzerland^[484]. In October 2018, data from the study was presented at the 43^rd European Society for Medical Oncology Congress (ESMO-2018)^[485].

AstraZeneca and M.D. Anderson Cancer Center, in July 2016, initiated a phase I/II trial to assess the safety and efficacy of the combination of durvalumab 750mg, carboplatin and paclitaxel 80mg in patients with high-grade epithelial non-mucinous ovarian, primary peritoneal or fallopian tube cancers (2015-0900; NCT02726997). The open-label, single-group trial will enrol approximately 35 patients in the US^[486]. In April 2020, results from the trial were presented at the 111^thAnnual Meeting of the American Association for Cancer Research (AACR-2020)^[487].

The Roswell Park Cancer Institute, in collaboration with the National Cancer Institute (NCI), plans to initiate a phase I/II trial that will evaluate the efficacy of durvalumab, in combination with olaparib [see AdisInsight drug profile 800024096] and tremelimumab [see AdisInsight drug profile 800020650], in the treatment of recurrent platinum sensitive or resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in female adult patients with a BRCA1 or BRCA2 mutation (I 288216; NCI-2016-01598; P30CA016056; NCT02953457). The open label, single group study intends to recruit approximately 39 adult female patients in the US^[488].

Pancreatic cancer

Prior to February 2017, AstraZeneca and MedImmune terminated the phase II/III ALPS registrational trial of durvalumab in combination with tremelimumab, for the treatment of metastatic pancreatic ductal carcinoma due to safety and efficacy reasons. The study was initiated in the fourth quarter of 2015. Based on the results of the study, filings are planned in the US, the EU and Japan in 2017 (AstraZeneca pipeline, February 2017) (Medimmune pipeline, September 2016).

In September 2021, M.D. Anderson Cancer Center initiated a phase II trial to evaluate the effects of gemcitabine, nab-paclitaxel, durvalumab, and oleclumab in treating patients with primary pancreatic cancer that may be able to be removed by surgery (resectable/borderline resectable) (NCT04940286; 2020-0898; NCI-2021-05721). The open-label trial intends to enroll approximately 30 patients in the US^[489].

In May 2020, AstraZeneca initiated the phase II MIMIPAC trial to evaluates the effectiveness of minimally invasive microwave ablation (MIS-MWA) combined with durvalumab plus tremelimumab [see Adis Insight Drug Profile800020650] in patients with unresectable non-metastatic locally advanced pancreatic cancer (UZ S61508; EudraCT 2018-002852-34; NCT04156087). Combination of durvalumab (fixed dose of 1500 mg) and tremelimumab (fixed dose of 75 mg) will be given 2 weeks before surgery and ystemic gemcitabine will be started 6 weeks after MIS-MWA.The open-label trial intends to enrol approximately 20 patients in Belgium^[490].

In November 2018, AstraZeneca and Seoul National University Hospital initiate a phase II trial to evaluate combination of chemoradiation therapy (CCRT/gemcitabine) and durvalumab as neoaduvant treatment followed by adjuvant gemcitabine/durvalumab in resectable or borderline resectable pancreatic cancer patients (NCT03572400; ESR-16-12315). The trial intends to enrol 71 patients in South Korea^[491].

In June 2018, MedImmune initiated a phase Ib/II study to evaluate the safety, pharmacokinetics, and antitumour activity of oleclumab [see AdisInsight drug profile 800042969] with or without durvalumab plus chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma patients (D6070C00005;EudraCT2018-001028-21; NCT03611556). The randomised, open-label trial intends to enrol approximately 339 patients in the US, Australia, Norway and Spain^[492]. In June 2023, efficacy and safety results from the trial 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) ^[493]

In April 2019, University of Colorado in collaboration with AstraZeneca withdrawed a phase II trial (cancelled by PI) (16-0546cc; NCT03038477). The trial was initiated in June 2017 that was designed to evaluate efficacy of durvalumab as an adjuvant therapy in patients with borderline resectable pancreatic ductal adenocarcinoma. The randomised, open-label trial intended to enrol approximately 114 patients in the US^[494].

University of Maryland is planning to initiate a phase II trial to evaluate combination of radiation therapy and durvalumab in metastatic pancreas cancer patients who have progressed through first-line chemotherapy (HP-00070528; NCT02885727). The trial intends to enrol 55 patients in the US^[495].

AstraZeneca and Canadian Cancer Trials Group, in August 2016, initiated a phase II trial to assess the safety and efficacy of gemcitabine plus nab-paclitaxel versus gemcitabine, nab-paclitaxel, tremelimumab and durvalumab, as a first-line therapy in patients with metastatic pancreatic ductal adenocarcinoma (PA7; NCT02879318). The randomised, parallel, open-label trial will enrol approximately 180 patients in Canada^[496].

AstraZeneca is planning to conduct a phase II trial to investigate durvalumab plus tremelimumab [see AdisInsight drug profile 800020650] in combination with targeted therapies (AZD 5069) for the treatment of patients with pancreatic ductal adenocarcinoma as a second-line therapy^[497].

In May 2017, AstraZeneca completed the phase II ALPS trial that assessed the efficacy of durvalumab, alone or in combination with tremelimumab, as second-line therapy in patients with metastatic pancreatic ductal adenocarcinoma (D4198C00001; NCT02558894; EudraCT2015-002001-11). The primary endpoint was objective response rate, assessed up to 3 years. The randomised, open-label trial was initiated in November 2015 and enrolled 95 patients in the US, Canada, Netherlands, South Korea, Germany and Spain^[498].

In August 2020, AstraZeneca and Cedars-Sinai Medical Center reinitiated the phase I/II DurvaRad trial to evaluate the safety and tolerability of durvalumab in combination with stereotactive ablative radiotherapy (SABR), a standard radiation treatment, for patients with borderline resectable and locally advanced pancreatic cancer (NCT03245541; IIT2016_01Tuli-DURVARAD). The open-label trial intends to recruit approximately 36 patients in the US^[499].

AstraZeneca completed phase Ib/II trial in July 2018, that evaluated. the safety, tolerability, pharmacodynamics and anti-tumour activity of durvalumab in combination with chemotherapy and novel anticancer agents in patients with pancreatic ductal adenocarcinoma (PDAC) (D4198C00003; NCT02583477; EudraCT2015-003639-37). This study consisted of two independent cohorts, which will involve the combination of durvalumab with nab-paclitaxel + gemcitabine [see AdisInsight drug profiles 800016962 and 800000811] chemotherapy regimen and durvalumab + AZD 5069 [see AdisInsight drug profile 800030696]. The non-randomised and open-labelled trial was initiated in March 2016 and enrolled 23 patients in the UK and the US^[500].

In April 2019, Eli Lilly and AstraZeneca completed a phase Ib trial that assessed the safety and efficacy of galunisertib [see AdisInsight drug profile 800028406] in combination with durvalumab in patients with recurrent or refractory metastatic pancreatic cancer (15784; H9H-MC-JBEG; EudraCT2015-005295-26; NCT02734160). The dose-escalation and cohort-expansion, single-group, open-label trial was initiated in June 2016 and enrolled 42 patients in the US, South Korea, France, Spain and Italy^[501].

In March 2019, AstraZeneca and New York University School of Medicine terminated a phase Ib study due to low accrual that was designed to determine the safety, recommended phase II dose (RP2D) and efficacy of (A) durvalumab alone, (B) tremelimumab alone or (C) the combination of durvalumab and tremelimumab [see AdisInsight drug profile800020650] along with Stereotactic Body Radiation Therapy in patients with unresectable locally advanced adenocarcinoma of pancreas (NYU S14-01317; NCT02868632). The non-randomised, parallel, open-label, three-cohort trial was initiated in August 2016 and approximately enrolled 36 patients in the US^[502].

In May 2018, NewLink Genetics announced that pancreatic cancer was deprioritized and the company has mutually agreed with AstraZeneca not to proceed with the phase II trial^[503]. NewLink Genetics Corporation and AstraZeneca had planned the Indigo201 phase II, randomised, double-blind, placebo-controlled trial of indoximod in combination with durvalumab [see AdisInsight drug profile 800027736] along with standard of care chemotherapy for patients with metastatic pancreatic cancer. The trial was to be funded by both the companies^[14]^[504].

Lymphoproliferative disorders

Before September 2017, as per the FDA recommendation, Celgene in collaboration with Memorial Sloan Kettering Cancer Center terminated a phase I trial (NCT03196401; 17-269). The trial was initiated in July 2017 to evaluate the abscopal effect of durvalumab, in combination with definitive radiation therapy, in solitary bone plasmacytoma with limited clonal bone marrow plasmacytosis. The open-label trial was intended to enrol 20 patients in the US^[505].

Prostate cancer

In October 2020, AstraZeneca initiated a phase II trial to evaluate the effects of durvalumab and olaparib in treating prostate cancer in men predicted to have specific genetic mutations (a high neoantigen load) (10509; NCI2020-01860; NCT04336943; P30CA015704; RG1007001). The pilot, open label trial intends to enrol 30 patients in the US^[506].

In August 2022, AstraZeneca completed the phase II AARDVARC trial that assessed the efficacy, safety, and tolerability of durvalumab in combination with AZD 4635 [see Adis Insight Drug Profile 800046147], alongside the exploration of a combination therapy with cabazitaxel and durvalumab, in patients with progressive metastatic castrate-resistant prostate cancer (NCT04495179; EudraCT2020-000209-10; D8731C00002). The open label, non-randomised trial was initiated in August 2020 and enrolled 30 patients in the US, South Korea, Belgium, Denmark, France, Germany, Italy, Spain and Netherlands^[507].

In April 2023, AstraZeneca completed a phase II trial that assessed the safety, efficacy, and tolerability of imaradenant [see AdisInsight drug profile 800046147], in combination with other therapeutic agents, including durvalumab and oleclumab [see AdisInsight drug profile 800042969], for metastatic castration-resistant prostate cancer (NCT04089553; D8731C00001; GU 156). The non-randomised, open-label, multi-drug trial was initiated in August 2019, and enrolled 59 participants in the US^[508].

In March 2019, AstraZeneca and Institut Cancerologie de l'Ouest initiated the phase II POSTCARD trial to evaluate stereotactic body radiation therapy (SBRT; 3x 9 or 3 x 11 Gy) with or without durvalumab (1500 mg/cycle) in oligometastatic recurrent hormone sensitive prostate cancer patients (ICO-N-2017-08; NCT03795207). The open-label, randomised trial intends to enrol approximately 96 patients in France^[509].

In April 2021, M.D. Anderson Cancer Center, in collaboration with Medimmune, completed a phase II trial that explored the link between immunological changes, efficacy, safety and tolerability of durvalumab plus tremelimumab [see AdisInsight drug profile 800020650] in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (NCT03204812). This open-label trial initiated in July 2017 enrolled 31 patients in the US^[510].

In May 2016, AstraZeneca in collaboration with Canadian Cancer Trials Group initiated a phase II trial to evaluate the efficacy and safety of durvalumab alone or in combination with tremelimumab [see AdisInsight drug profile 800020650] in patients with metastatic castration resistant prostate cancer (NCT02788773; 1232). The open, parallel, prospective, randomised trial is recruiting approximately 74 patients in Canada. The primary endpoint ORR (RECIST1.1 and iRECIST) using a Simon 2-stage design. Key secondary endpoints were PSA response rate (RR) and time to progression (TTP). In September 2019, the safety results were presented at the 44th European Society for Medical Oncology Congress (ESMO-2019)^[511]^[512].

The University of Washinton and the National Cancer Institute plans to initiate a phase II trial to evalaute the efficacy of durvalumab in hypermutated metastatic, castration-resistatnt prostate cancer (9768, NCI-2016-01618, 9768, P30CA015704, NCT02966587). The response rate to durvalumab in terms of modified RECIST 1.1 criteria or a reduction in PSA level >= 50% will be evaluated as priamry endpoint measure in the trial. The open-label, single-group assignment trial will enrol 28 patients in the US^[513].

Pulmonary sarcomatoid carcinoma (lung cancer in development table)

Seoul National University Hospital is planning a phase II study to evaluate the efficacy and safety of durvalumab plus tremelimumab regimen in patients with pulmonary sarcomatoid carcinoma (NCT03022500). Approximately 18 subjects will be enrolled in South Korea^[514].

Renal cell carcinoma

In November 2017, University College, London in collaboration with AstraZeneca initiated the phase III RAMPART trial to assess the efficacy of durvalumab monotherapy and durvalumab/tremelimumab combination therapy compared with standard of care regimen, in patients with resected primary renal cell carcinoma at high or intermediate risk of relapse, in adjuvant setting (MRC RE06; ISRCTN53348826; EudraCT2017-002329-39, NCT03288532). The randomised, open-label trail is designed to enrol approximately 1750 patients in the UK^[515].

In December 2017, AstraZeneca and Big Ten Cancer Research Consortium, initiated a phase Ib/II trial to investigate the efficacy and safety of durvalumab 1500 mg IV, in combination with guadecitabine (60 mg/m² or 45 mg/m²) subcutaneously [see AdisInsight drug profile 800025573], in patients with advanced renal cancer, renal cell carcinoma (BTCRC-GU16-043; NCT03308396). The single arm study is enrolling approximately 58 patients in the US^[516]. Safety and efficacy results from the phase Ib part of the trial were presented at the 45th European Society for Medical Oncology Congress (ESMO-2020)^[517].

In May 2016, AstraZeneca initiated a clinical trial to assess the safety and efficacy of durvalumab alone or in combination with savolitinib or tremelimumab in patients with metastatic renal cell carcinoma (178883; UKCRN30435). The trial is recruiting patients in the UK, France and Spain^[518].

Small cell lung cancer

As of August 2022, Durvalumab (Imfinzi^®) is available in Netherlands for treatment of patients with small cell lung cancer (SCLC)

In September 2020, durvalumab has been approved in the European Union for the 1st-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin. The approval by the European Commission was based on positive results from the phase III CASPIAN trial showing durvalumab plus chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit for the 1st-line treatment of patients with ES-SCLC. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2020^[519].

In March 2020, AstraZeneca announced that durvalumab has been approved in the US as a first line treatment for adult patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with standard-of-care (SoC) chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide). The approval by the US Food and Drug Administration was based on positive results from the Phase III CASPIAN trial [see below]. Earlier in November 2019, AstraZeneca announced that the US FDA has accepted a supplemental Biologics License Application (sBLA) for durvalumab for the treatment of patients with previously untreated extensive-stage small cell lung cancer (SCLC) and granted priority review for the same. The drug is available in the US for small cell lung cancer^[520]^[521].

In July 2021, durvalumab was approved by National Medical Products Administration for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with standard of care platinum chemotherapy (etoposide plus a choice of either carboplatin or cisplatin), in China. The approval was based on positive results from the CASPIAN phase III trial ^[522].

In fourth quarter of 2019, AstraZeneca announced that the European Union has accepted a regulatory submission for durvalumab for the treatment of extensive small cell lung cancer^[382].

As of March 2020, durvalumab is approved in Singapore for the treatment of extensive-stage small cell lung cancer in combination with standard of care chemotherapy^[523].

In August 2020, durvalumab (Imfinzi) was approved by the Japanese Ministry of Health, Labour and Welfare as a first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with etoposide plus a choice of platinum chemotherapy (either carboplatin or cisplatin), based on positive results from the phase III CASPIAN trial^[524]. AstraZeneca filed a regulatory submission with the Pharmaceuticals and Medical Devices Agency of Japan in fourth quarter of 2019^[382].

In July 2019, the US FDA granted orphan drug designation to durvalumab, for the treatment of small cell lung cancer^[525].

In March 2023, AstraZeneca completed the phase IIIb Oriental trial that determined the safety of durvalumab plus etoposide and cisplatin or carboplatin as first-line treatment in patients with extensive stage small-cell lung cancer (NCT04449861; D419BR00018). The open-label, single-arm study was initiated in December 2020 and enrolled 166 patients, in China^[526]. Prior to November 2020, AstraZeneca submitted regulatory application for the approval of durvalumab in the treatment of patients with extensive-stage small cell lung cancer in China^[71].

In June 2020, AstraZeneca completed the ADRIATIC phase III trial that assessed the efficacy of of durvalumab or durvalumab and tremelimumab as consolidation therapy in patients with small-cell lung cancer (D933QC00001; NCT03703297). The randomised, triple-blind trial was initiated in September 2018 and enrolled 600 patients in Russia, the US, Belgium, Canada, Argentina, China, Czech republic, Germany, India, Italy, Japan, South Korea, Netherlands, Spain, Taiwan, Turkey and Vietnam^[527]. In March 2024, AstraZeneca announced that the results from the trial showed durvalumab demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer and the safety profile was consistent with its known profile, and no new safety signals were identified^[528].

In March 2017, AstraZeneca initiated the phase III CASPIAN trial to assess the efficacy of durvalumab or durvalumab and tremelimumab [see AdisInsight drug profile 800020650], in combination with platinum-based chemotherapy for the first-line treatment in patients with extensive stage small-cell lung cancer (D419QC00001; EudraCT2016-001203-23; NCT03043872). The open-label, parallel trial enrolled 988 patients in Bulgaria, Czech Republic, Hungary, Russia, South Korea, Slovakia, Spain, the Netherlands, Argentina, Austria, Brazil, France, Germany, Israel, Italy, Poland, Romania, Taiwan, Turkey, Japan, Ukraine and the US. In June 2019, an Independent Data Monitoring Committee conducted an interim analysis, concluding the trial met its primary endpoint by showing a statistically significant and clinically meaningful improvement in overall survival in patients, treated with durvalumab, in combination with standard-of-care etopos ide and platinum-based chemotherapy options versus chemotherapy alone. However, the second experimental arm testing tremelimumab, added to durvalumab and SoC did not meet its primary endpoint of demonstrating a statistically significant improvement in OS in the analysis. In May 2020, updated efficacy and safety data from the trial was presented at the American Society of Clinical Oncology (ASCO-2020). Updated results were announced by AstraZeneca. In September 2021, updated efficacy and safety data were released by AstraZeneca^[529]^[414]^[530]^[520]^[531]^[532]^[533]^[534]. In April 2022, the company presented updated results of this trial at the 113th Annual Meeting of the American Association for Cancer Research (AACR-2022)^[535]. In June 2022, adverse events data from the trial were presented at the 58^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[536].

In June 2020, Samsung Medical Center in collaboration with AstraZeneca initiated the phase II SUKSES-N4 trial to evaluate the efficacy of ceralasertib (AZD 6738) [see Adis Insight drug profile800039325] and durvalumab combination therapy in patients with relapsed small cell lung cancer (SCLC) as a second or third line che AdisInsight drug profile 800037095] or durvalumab and tremelimumab as consolidation therapy in patients with small-cell lung cancer (D933QC00001; NCT03703297). The randomised, triple-blind trial was initiated in September motherapy (2020-02-103; NCT04361825). The open-label trial intends to enrol approximately 45 patients in South Korea^[537].

In November 2016, AstraZeneca initiated a phase II trial to assess the preliminary efficacy, safety, tolerability and immunogenicity of two combinations, A) AZD 1775 + carboplatin [see AdisInsight drug profile 800028808] B) durvalumab + tremelimumab followed by durvalumab monotherapy, in patients with platinum refractory or resistant extensive-stage SCLC (BALTIC; D419QC00002; EudraCT2016-001202-42; NCT02937818). The non-randomised, parallel, open-label, signal-searching study is enrolling approximately 80 patients in Germany, Hungary, Poland, Spain, Ukraine and will expand to the US^[538]. In October 2018, preliminary efficacy and safety results from the trial were presented by AstraZeneca at the 43^rdEuropean Society for Medical Oncology Congress (ESMO-2018)^[539]. In April 2022, AstraZeneca presented efficacy and safety data from the trial at 113^th Annual Meeting of the American Association for Cancer Research (AACR-2022)^[540].

In August 2020, AstraZeneca and Emory University completed a phase II trial that assessed the efficacy of tremelimumab [see AdisInsight drug profile 800020650] and durvalumab combination therapy with or without radiation therapy in patients with relapsed small cell lung cancer (IRB00086004; NCI-2016-00026; ESR-14-10531; Winship3112-15; NCT02701400). The randomised, parallel, open-label trial was initiated in April 2016 and enrolled 18 patients in the US. In May 2019, Emory University presented safety and efficacy results at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[541]^[542].

In January 2022, Trans Tasman Radiation Oncology Group in collaboration with AstraZeneca initiated a phase II CHEST RT trial of platinum and etoposide chemotherapy, durvalumab with thoracic radiotherapy in the first line treatment of patients with extensive-stage Small-cell lung cancer (NCT05796089; 381223; TROG 20.01 CHEST RT; ACTRN12621000586819p). The open label, single arm trial intends to enroll approximately 35 patients in Australia^[543].

Squamous cell cancer

In March 2022, Southwest Oncology Group in collaboration with National Cancer Institute completed a phase II clinical trial of durvalumab in combination with tremelimumab [see AdisInsight RDI 800020650] as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-Map Non-Match Sub-Study) (NCT03373760; S1400F; NCI-2016-01597; U10CA180888). The open-label trial was initiated in October 2017, and enrolled 67 patients in the US ^[544].

Solid tumours

Before June 2023, University Health Network terminated the SOLID phase II basket study to evaluate combination of olaparib [see Adis profile 800024096] and durvalumab in patients with IDH-mutated solid tumours including glioma, cholangiocarcinoma and other solid tumours due to ack of efficacy (NCT03991832; 19-5526). The single arm, open-label trial was initiated in December 2019 and enrolled 10 participants in Canada^[545]. In June 2021, data from the trial were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021)^[546]. In June 2023, safety and efficacy results from the trial were presented at the 59^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023)^[547].

In September 2021, Astra Zeneca completed the phase I/II MEDIOLA trial that evaluate the effect of durvalumab 50 mg/ml IV infusion in combination with olaparib [see AdisInsight drug profile800024096] (100mg and 150mg) film-coated tablet on disease control rate in patients with advanced solid tumours (D081KC00001; EudraCT2015-004005-16; NCT02734004). The trial will also assess the anti-tumour activity, safety and tolerability of the combination therapy in patients with selected advanced solid tumours, including small cell lung cancer, breast cancer, ovarian cancer and gastric cancer. The open-label trial initiated in March 2016, enrolled 264 patients in the US, France, Israel, South Korea, Netherlands, Switzerland, and the UK. Preliminary safety and efficacy data from the breast cancer cohort were presented at the 40th Annual San Antonio Breast Cancer Symposium (SABCS-2017). The company presented safety data at the 44th European Society for Medical Oncology Congress (ESMO-2019)^[548]^[404]^[549]. In September 2022, Astra Zeneca presented efficacy data from the trial at 47th Congress of European Society for Medical Oncology (ESMO-2022)^[550].

In March 2022, AstraZeneca terminated a phase I trial that was designed to assess the safety and tolerability of durvalumab in combination with tremelimumab [see ADIS Insight Drug profile800020650] in combination with carboplatin plus (+) etoposide in treatment naive patients with extensive-stage small cell lung cancer (ES-SCLC) and performance status 2 (PS2) (NCT03963414; 275-19). The open-label trial was initiated in June 2020 and enrolled 1 patients in the US^[551].

In October 2021, Medimmune completed the phase I/II trial for monalizumab [see Adis Insight Drug profile800034739] in combination with durvalumab in patients with advanced solid tumours (NCT02671435; EudraCT2016-000662-38; D419NC00001). In May 2018, Innate Pharma released preliminary data from a phase I trial, designed to evaluate the safety, tolerability, anti-tumour activity, and immunogenicity of monalizumab in combination with durvalumab (MEDI 4736) in patients with advanced solid tumours. The company had amended the trial protocol and included expansion cohort of patients with first and second-line, metastatic colorectal cancer, in March 2018. The dose-escalating part of the study has been completed. The trial was initiated by Innate Pharma, in collaboration with MedImmune, in February 2016. The open-label, dose-escalation, cohort-expansion study enrolled 383 participants in Canada, France, Hungary, Italy, Spain, United Kingdom, the US, South Korea, Australia, Belgium, New Zealand. Updated positive results released in June 2018 have prompted further expansion of the study with cohorts including patients with less heavily pre-treated disease Updated safety data were presented by the company at the 44th European Society for Medical Oncology Congress (ESMO-2019)^[552]^[553]^[554]^[555]^[556]^[557]. In March 2021, Innate Pharma announced that it expanded a phase II expansion cohort (cohort 3), to explore the combination of monalizumab, cetuximab and durvalumab in first-line IO naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), in 20 to 40 patients. The company also announced that the recruitment of patients for cohort 3 is complete ^[558]. In December 2021, Innate Pharma released data from the phase II expansion cohort (cohort 3) of the trial demonstrating anti-tumour activity of the triplet combination of monalizumab, cetuximab and durvalumab in the first-line treatment of R/M SCCHN ^[559].

In February 2023, AstraZeneca, in collaboration with Stanford University, discontinued a phase II study due to low accrual as per results, which was designed to evaluate the safety and tolerability of durvalumab in combination with chemotherapy in patients with bladder cancer (NCI-2019-01364; BLDR0028; IRB-48062; NCT03912818). The open-label study was initiated in April 2019, and enrolled six patients in the US^[560].

In April 2017, AstraZeneca initiated the phase III STRONG trial to evaluate the safety of durvalumab monotherapy or in combination with tremelimumab [see AdisInsight drug profile 800020650] in patients with advanced solid tumours (D4191C00068; NCT03084471). The open-label trial completed enrolment of 867 patients in the US, Canada, France, Germany, Italy, the Netherlands, South Korea and the UK, in November 2019^[561].

In March 2017, M.D. Anderson Cancer Center in collaboration with AstraZeneca initiated a phase II trial to evaluate the efficacy and safety of AZD 9150 [see AdisInsight drug profile 800021483] in combination with durvalumab (MEDI 4736) in patients with advanced pancreatic cancer, non-small cell lung cancer mismatch repair deficient colorectal cancer (NCT02983578; 2016-0108). The multicenter, open-label, dose-escalation and dose-expansion trial intends to enrol approximately 140 patients in the US and France^[562].

In September 2016, The University Health Network, Toronto, initiated the phase II METADUR trial, to assess anti-tumour activity of durvalumab in combination with azacitidine, in patients with solid tumour (METADUR-001; NCT02811497). The open-label trial intends to enrol approximately 60 patients in Canada^[563].

In August 2016, AstraZeneca and Canadian Cancer Trials Group initiated a phase II trial to assess the safety and efficacy of tremelimumab [see AdisInsight drug profile 800020650] in combination with durvalumab in patients with advanced rare tumours, which includes salivary carcinoma, carcinoma of unknown primary with tumour infiltrating lymphocytes (TILs) and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary and squamous cell carcinoma of the anal canal (I228; NCT02879162). The open-label, single-group trial intends to enrol approximately 160 patients in Canada^[564].

In January 2016, Astra Zeneca initiated a phase II trial to evaluate the effect of durvalumab 50 mg/ml IV infusion in combination with olaparib (100mg and 150mg) film-coated tablet [see AdisInsight drug profile 800024096] on disease control rate in patients with advanced solid tumours (D081KC00001; EudraCT2015-004005-16). The trial will also assess the anti-tumour activity, safety and tolerability of the combination therapy in patients with selected advanced solid tumours, including small cell lung cancer, breast cancer, ovarian cancer and gastric cancer. The open-label trial is recruiting 139 patients in the Netherlands, the UK and will extend to France, Israel, South Korea, Switzerland and the US^[404]^[549].

In June 2015, AstraZeneca presented data on durvalumab in combination with tremelinumab [see isInsight drug profile 800020650]. The combination therapy demonstrated efficacy regardless of PD-L1 status, showing promise for patients who fail anti-PD-1/PD-L1 monotherapy because of their PD-L1 biomarker negative status. The combination also had a manageable safety profile, with a 7% discontinuation rate due to related adverse events. The company plans to explore the combination therapy in other tumour types, including gastric, pancreatic and bladder cancer. Additional data that was presented included durvalumab in combination with and BRAF and MEK inhibitors, durvalumab in combination with mereletinib [see AdisInsight drug profile 800037784] and durvalumab in combination with gefitinib [see AdisInsight drug profile 800007340].

MedImmune, AstraZeneca and Greenville Health System, in December 2016, initiated a phase II trial to assess the anti-tumour activity, safety and tolerability of tremelimumab in combination with durvalumab in patients with select advanced rare solid tumours (ESR-15-11633; NCT02938793). The open-label, single-group study will enrol approximately 100 patients in the US^[565].

In March 2023, AstraZeneca completed a phase II trial that evaluated the safety and efficacy of durvalumab as a monotherapy and in combination with tremelimumab [see AdisInsight drug profile 800020650] in patients with advanced solid tumours (D4884C00001; NCT02527434; 2015-002934-32). This open-label trial was initiated in November 2015 and enrolled 64 patients in South Korea, the US, Belgium, the Netherlands and Poland^[566].

In September 2021, AstraZeneca announced that trial met its primary efficacy endpoint. In October 2020, AstraZeneca re-initiated phase I/II MOVIE trial which was earlier suspended in April 2020 due to COVID-19 pandemic. The trial was initiated in June 2018 to evaluate the safety and activity of metronomic oral vinorelbine associated with durvalumab plus tremelimumab combination immunotherapy for the treatment of advanced solid tumours (NCT03518606; UC-101-1709). The open-label trial intended to enrol approximately 150 patients in France^[567]. In September 2020, Pierre Fabre presented the safety data at the 45th European Society for Medical Oncology Congress (ESMO-2020)^[568]^[569]. In September 2021, efficacy and adverse events data from a trial was presented at the 46th European Society for Medical Oncology Congress (ESMO-2021)^[570]^[571].

In June 2017, Gustave Roussy initiated a phase I/II trial to evaluate the safety, and clinical activity of durvalumab + tremelimumab [see AdisInsight drug profile 800020650] antibodies administered in combination with Stereotactic Body Radiotherapy (SBRT) in patients with metastatic squamous cell carcinoma of head and neck, lung, or oesophagus (2016/2454; EudraCT2016-003293-40; NCT03212469). The open-label trial intends to enrol approximately 40 patients in France.

In November 2017, Eli Lilly and AstraZeneca terminated a phase Ia/Ib trial that was designed to assess the safety and tolerability of durvalumab and LY 2510924 SC [see AdisInsight drug profile 800034546] in patients with advanced refractory solid tumours (16387; I2V-MC-CXAD; NCT02737072). The open-label, parallel, non-randomised trial was initiated in September 2016 and intended to enrol approximately 45 patients in the US^[572].

In September 2018, Innate Pharma and MedImmune initiated the phase I STELLAR-001 trial to evaluate IPH 5401[see AdisInsight drug profile800036376], in combination with durvalumab in patients with solid tumours, including non-small-cell lung cancer with secondary resistance to prior immuno-oncology (IO) treatment and IO-naive liver cancer (IPH5401-101; NCT03665129). The two-part study design includes an initial dose escalation phase to explore three doses of IPH5401 in combination with durvalumab, followed by dose expansion part. The open label trial is enrolling 100 patients in the US and France^[573]^[574]. Preclinical data suggested that C5aR blockade increased immune-mediated tumour killing and efficacy of checkpoint inhibitors^[9]. In March 2022, updated data from the study was presented at the 20th International Congress on Targeted Anticancer Therapies (TAT-2022). In September 2019, Innate Pharma presented the adverse events data from a phase I STELLAR-001 trial in solid tumours presented at the 44th European Society for Medical Oncology Congress (ESMO-2019)^[575]^[576].

AstraZeneca is planning to initiate another clinical trial of AZD 9150 with durvalumab^[577].

In November 2020, AstraZeneca completed its phase I/II trial that assessed the safety, tolerability, pharmacokinetics and anti-tumour activity of durvalumab alone and in combination with tremelimumab in patients with advanced solid malignancies (phase I cohort), including nasopharyngeal carcinoma (phase II cohort) (D419AC00006; NCT02978482). The open-label, parallel, non-randomised trial was initiated in December 2016 and enrolled 26 patients in China^[578].

In August 2017, Pharmacyclics completed a phase Ib/II trial that evaluated the safety and efficacy of durvalumab in combination with ibrutinib [see AdisInsight drug profile 800022023], in patients with relapsed or refractory solid tumours including breast cancer, NSCLC and pancreatic cancer (PCYC-1135-CA; NCT02403271). The open-label trial was initiated in March 2015, and enrolled 124 patients in the US. Ibrutinib (560 mg, daily) and durvalumab, 10 mg/kg every two-week was identified as the recommended phase II dose. Data from the trial were presented at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[579]^[580]^[581].

In August 2015, NCIC and AstraZeneca initiated a phase Ib trial to assess the safety and efficacy of durvalumab alone and in combination with tremelimumab in patients with advanced and incurable solid malignancies undergoing standard chemotherapy regimens (I226; NCT02537418). This study will determine the recommended phase II dose and will enrol 150 patients in Canada. Updated results were presented at the 44^th European Society for Medical Oncology Congress (ESMO-2019)^[582]^[583].

In August 2014, MedImmune initiated a phase Ib/II study to evaluate the safety and efficacy of MEDI 6469 in combination with tremelimumab, durvalumab or rituximab in patients with either advanced solid tumours or diffuse large B-cell lymphoma (NCT02205333). The study will also determine the maximum tolerated dose of MEDI 6469 when administered as a monotherapy and as a part of a combination regimen. MEDI 6469 will be assessed with tremelimumab and durvalumab in patients with advanced solid tumours, whereas the MEDI 6469 plus rituximab regimen will be evaluated in patients with diffuse large B-cell lymphoma. Recruitment of approximately 252 patients is underway in the US^[584]. [see AdisInsight drug profiles 800020650, 800035174 and 800004275].

In October 2020, MedImmune in collaboration with Incyte Corporation completed a phase I/II trial that evaluated the durvalumab in combination with Incyte's IDO1 inhibitor epacadostat [see AdisInsight drug profile 800025047] in patients with solid tumours, including metastatic melanoma, NSCLC, squamous cell carcinoma of the head and neck and pancreatic cancer (NCT02318277). The open labe trial was initiated in January 2015, and enrolled 176 patients in the US^[585].

In February 2020, Medimmune completed the phase I/II trial that examined the safety, tolerability and pharmacokinetics of durvalumab in patients with solid tumours (CD-ON-MEDI4736-1108; EudraCT2012-002206-52; NCT01693562). The study was initiated in August 2012 and enrolled 1022 patients in the US, Belgium, Canada, France, Germany, Italy, South Korea, Taiwan and the UK^[220]. In June 2016, AstraZeneca presented preliminary results of 61 patients with advanced urothelial bladder cancer from the trial at American Society of Clinical Oncology (ASCO) Annual Meeting^[586]. In October 2016, positive preliminary results from the study were presented at the 41^st European Society for Medical Oncology Congress (ESMO-2016). Updated results from the trial, displaying a durable response of durvalumab, were released by the company in February 2017. In June 2017, MedImmune presented pooled efficacy and safety data of the ATLANTIC (see above) and 1108 trial at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO-2017). In June 2018, safety and efficacy data from the trial was presented at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[587]^[438]^[439]^[588]^[589]^[590]^[248]^[300]^[591]. In April 2023, updated efficacy data from the trial was presented at 114th Annual Meeting of the American Association for Cancer Research (AACR-2023)^[592]

In September 2017, Targovax and MedImmune, in collaboration with Ludwig Institute for Cancer Research initiated a phase I/II study to investigate the safety and efficacy of durvalumab in combination with ONCOS 102 [see AdisInsight drug profile 800033483] in patients with advanced peritoneal malignancies, who have failed prior standard chemotherapy and have histologically confirmed platinum-resistant or refractory epithelial ovarian cancer or colorectal cancer (LUD2015-008; NCT02963831). The trial intends to enrol approximately 78 patients in the US^[593]. In July 2018, the safety evaluation for the first dose cohort^[594].

In February 2022, MedImmune, in collaboration with the Ludwig Institute for Cancer Research and Cancer Research Institute completed a phase I/II trial of in situ vaccination with tremelimumab and IV durvalumab [see AdisInsight drug profile [500037095]] in combination with the tumour microenvironment (TME) modulator polyICLC, in subjects with advanced, measurable, biopsy-accessible cancers, including head and neck cancer, breast cancer, sarcoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, malignant melanoma, renal cancer, bladder cancer and prostate cancer (NCT02643303; LUD2014-011). The non-randomised, parallel-assignment trial was initiated in December 2016 and enrolled 58 patients in the US^[595].

In May 2018, AstraZeneca initiated the phase I CLOVER trial to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumours (D933BC00001; NCT03509012). The open, parallel, prospective trial is enrolling approximately 300 patients in Japan, Spain, South Korea, Taiwan and the US^[596]. In September 2020, interim safety data from the trial was presented at the 45^thEuropean Society for Medical Oncology Congress (ESMO-2020)^[597].

In March 2017, Medimmune initiated a phase I trial to evaluate the safety, pharmacokinetics and immunogenicity of MEDI 5083 [see AdisInsight drug profile 800049207 alone and in combination with durvalumab in selected advanced solid tumours (D6840C00001; NCT03089645). The trial plans to enrol 204 patients in the US and Australia^[598].

In January 2020, MedImmune completed the phase I trial that assessed the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumour activity of MEDI 9090 [see AdisInsight drug profile800047888] plus durvalumab in adult patients with advanced solid tumours (D4190C00055; NCT02900157). The trial was initiated in August 2016 recruited 40 patients in the US and Japan^[599].

In July 2016, the Children's Hospital Los Angeles initiated a phase I, open-label, single institution study to assess the safety, tolerability, and pharmacokinetics of durvalumab in paediatric patients with relapsed or refractory solid tumours, lymphoma, and central nervous system tumours (ESR-14-10488; NCT02793466). The study is enrolling approximately 36 patients in the US^[600]^[601]. In June 2022, results from the trial were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022)^[602].

In January 2021, AstraZeneca and Eli Lilly and Company completed a phase I trial that evaluated the safety of ramucirumab [see AdisInsight drug profile 800021478] in combination with durvalumab in patients with advanced solid tumours/ gastrointestinal or thoracic malignancies including gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer, or hepatocellular carcinoma (NCT02572687; EudraCT2015-003013-14; 16116; I4T-MC-JVDJ). The non-randomised, open-label trial was initiated in February 2016, and enrolled 85 patients in the US, France, Germany, Israel, Italy, South Korea, Spain and Taiwan^[603]. Preclinical data of the combination therapy of vascular endothelial growth receptor inhibitors with immune checkpoint blockades demonstrated the potential to enhance the anti-tumour activity. In May 2019, efficacy and safety results from the trial were presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[604]^[23].

In November 2019, AstraZeneca completed a phase I trial that evaluated the safety and tolerability of durvalumab and tremelimumab [see AdisInsight drug profile 800020650], in combination with first-line chemotherapy in patients with advanced solid tumours (NCT02658214; D419SC00001). The open-label, non-randomised trial was initiated in April 2016, and enrolled 32 patients in South Korea and Japan^[605].

AstraZeneca, in December 2015, initiated a phase I trial to evaluate the safety, tolerability and pharmacokinetics of MK 1775 capsule [see AdisInsight drug profile 800028808] in combination with durvalumab IV infusion in patients with advanced or refractory solid tumours (D6015C00002; REFMAL 412; NCT02617277). The immunogenicity, pharmacodynamics and preliminary anti-tumour activity will also be determined. The dose-escalation/expansion, open-label, single-group trial will enrol approximately 18 patients in the US^[606]. In May 2019, efficacy, pharmacokinetics and safety data from the trial were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[607].

In collaboration with AstraZeneca, Kyowa Hakko Kirin initiated a phase I/Ib trial in November 2014 to investigate the safety, tolerability and efficacy of mogamulizumab in combination with durvalumab, and in combination with tremelimumab, in patients with advanced solid tumours (NCT02301130). The trial will enrol 108 patients in the US^[608]. The trial is being funded by both companies^[38].

In September 2019, AstraZeneca completed a phase I trial to investigate the safety, tolerability, pharmacokinetics and anti-tumour activity of durvalumab in combination with ascending doses of selumetinib [see AdisInsight drug profile 800019504] in patients with advanced solid tumour (D1345C00003; NCT02586987). The open-label, non-randomised trial was initiated in December 2015 and enrolled 58 patients in the US^[609].

In January 2021, Medimmune completed a phase I trial that assessed the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumour activity of oleclumab [see AdisInsight drug profile 800042969] alone and in combination with durvalumab in patients with select advanced solid tumours (D6070C00001; NCT02503774). The non-randomised, open-label trial was initiated in July 2015, and enrolled 192 patients in the US, Australia and South Korea^[610].

In January 2020, MedImmune completed a phase I study which assessed the safety, tolerability and anti-tumour activity of durvalumab, in combination with tremelimumab [see AdisInsight drug profile 800020650], in patients with advanced solid tumour (D4190C00010; NCT02261220). This open-label trial, which was initiated in October 2014, enrolled 380 patients in the US, Canada, France, Germany, Israel, South Korea, the Netherlands, Spain, the UK^[611]. In June 2018, safety and efficacy data were presented at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[612].

In September 2014, MedImmune initiated a non-randomised phase I trial to assess the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and anti-tumour activity of MEDI 6383 [see AdisInsight drug profile 800041453], alone or in combination with durvalumab, as a second-line or greater therapy in patients with recurrent or metastatic solid tumours (D6050C00001; NCT02221960). The trial will enrol approximately 212 patients in the US and Australia^[613]^[614].

AstraZeneca completed a phase I trial in January 2017, assessed safety, tolerability, pharmacokinetics and preliminary efficacy of durvalumab in combination with tremelimumab, compared to tremelimumab alone, patients with advanced solid tumours (D4880C00010; JapicCTI142553; NCT02141347). The non-randomised trial initiated in May 2014, enrolled 73 patients in Japan^[615].

In March 2020, MedImmune completed the uncontrolled phase I trial, that assessed the safety and tolerability of AMP 514 in combination with durvalumab [see AdisInsight drug profile 800037095] in patients with advanced cancers (D6020C00001; NCT02118337). The trial was initiated in May 2014 and enrolled 97 patients in the US^[616]. Interim efficacy, safety and immunogenicity data was presented at the 41^st European Society for Medical Oncology Congress (ESMO-2016) in October 2016^[617].

In July 2021, The Ludwig Institute for Cancer Research, in collaboration with Medimmune completed a phase I trial which evaluated the safety and tolerability of durvalumab, in combination with tremelimumab, in patients with advanced solid tumours (NCT01975831). The open label trial enrolled 104 patients in the US^[618].

AstraZeneca, in November 2020, completed a phase I trial that evaluated safety, tolerability and pharmacokinetics of escalating doses of durvalumab in patients with advanced solid tumours (NCT01938612; D4190C00002). The primary endpoint of the trial was to determine number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs) within 90 days after the last dose of durvalumab. This open-label trial was initiated in September 2013 and recruited 269 patients in Japan, South Korea and Taiwan^[619].

In December 2019, Plexxikon and AstraZeneca completed the MEDIPLEX phase I trial that evaluated the safety and efficacy of combination of durvalumab with plexidartinib [see AdisInsight drug profile 800031061] in patients with advanced/metastatic cancer including colorectal or pancreatic cancers (ET15-037; EudraCT2015-002438-31; NCT02777710). This dose escalation, open-label trial was initiated in July 2016 and enrolled 48 patients in France. The study was a 2-part study comprising a dose-finding escalation part (to determine maximum tolerated dose/recommended phase II dose, safety and PK) followed by an extension part at recommended phase II dose. In the dose-escalation part, successive cohorts of 3 patients received pexidartinib (given orally every day at escalating doses, five dose levels) in combination with durvalumab (given IV every 4 weeks at a fixed dose of 1500mg). In June 2019, data from the trial were presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[620]^[621].

AstraZeneca in collaboration with Peregrine plans a phase I/Ib trial to investigate the safety and efficacy of durvalumab in combination with bavituximab in patients with multiple solid tumours. However, as of March 2016, the trial was suspended by the company. The phase I part of the trial was planned to establish a recommended dose regimen for the combination, while the phase Ib part was planned to assess the safety and efficacy of the combination^[20]^[622].

Eli Lilly and AstraZeneca, in June 2016, initiated a phase Ia/Ib trial to assess the safety of IMC CS4 IV in combination with durvalumab IV or tremelimumab IV in patients with advanced solid tumours (16348; I5F-MC-JSCC; EudraCT2016-000427-11; NCT02718911). The dose-escalation/expansion, open-label, parallel, non-randomised trial is enrolling approximately 178 patients in the US, and will expand to France, Belgium, Germany, Israel, Italy, the Czech Republic^[24].

In August 2015, Peregrine entered into a non-exclusive clinical trial collaboration with AstraZeneca to conduct a phase I/Ib trial of bavituximab [see AdisInsight drug profile 800022616] in combination with AstraZeneca's durvalumab in multiple solid tumours. The phase I part of the trial will establish a recommended dose regimen for the combination, while the phase Ib part will assess the safety and efficacy of the combination. Pursuant to the terms of the agreement, Peregrine will conduct the initial phase I part of the trial^[20]^[622].

MedImmune in collaboration with Juno Therapeutics is planning to initiate a phase Ib trial during late 2015, to investigate the safety, tolerability and preliminary efficacy of durvalumab (MEDI 4736) in combination with anti-CD19 chimeric antigen receptors (CAR) transduced T cells [see AdisInsight drug profile 800041081] in patients with non-Hodgkin's lymphoma^[623]^[624]^[625].

AstraZeneca is planning to initiate clinical studies of durvalumab + AZD 9150 [see AdisInsight drug profile 800021483], in the first half of 2015^[626].

Multiple sarcoma subtypes

In August 2022, AstraZeneca completed the phase II MEDISARC trial that evaluated the efficacy of tremelimumab and durvalumab [See ADIS Insight Drug Profile 800037095] and in comparison to doxorubicin in treatment-naïve soft tissue sarcoma patients (NCT03317457; EudraCT2016-004750-15; AIO-STS0415). The open, parallel, prospective, randomised trial was initiated in December 2017 and enrolled approximately 103 patients in Germany^[627].

As of August 2022, the phase II study to evaluate the efficacy of the combination of durvalumab and tremelimumab [see AdisInsight drug profile 800020650] in multiple metastatic sarcoma was completed ^[628] (2015-1071; NCI-2016-01178; NCT02815995). Previously, In August 2016, M.D. Anderson Cancer Center in collaboration with MedImmune initiated a phase II study to evaluate the efficacy of the combination of durvalumab and tremelimumab in multiple metastatic sarcoma subtypes, including, epithelioid haemangioendothelioma, undifferentiated pleomorphic sarcoma, synovial sarcoma and osteosarcoma. The non-randomised open-label trial enrolled 62 patients in the US^[629]. In May 2020, efficacy and safety data from the trial were presented at the 56th American Society of Clinical Oncology meeting (ASCO-2020)^[630].

In June 2022, University of Maryland, in collaboration with University of Arizona and AstraZeneca, completed the phase I/II NEXIS trial that evaluated the efficacy of the combination of tremelimumab [see AdisInsight drug profile 800020650] and durvalumab, in patients with soft tissue sarcoma (HP-00073356; NCT03116529). The open-label trial was initiated in June 2017, and enrolled 22 patients in the US^[631].

Thyroid cancer

In June 2022, Memorial Sloan Kettering Cancer Center and AstraZeneca completed a phase I trial which evaluated the safety of durvalumab and tremelimumab [see AdisInsight drug profile800020650] in combination with radiation therapy for the treatment of thyroid cancer (17-108; NCT03122496). The open label trial was initiated in April 2017 and enrolled 13 patients in the US^[632].

Other NIO-sponsored trials

In December 2018, Jules Bordet Institute and AstraZeneca initiated a phase SYNERGY I/II trial of paclitaxel plus carboplatin and durvalumab (MEDI 4736) with or without oleclumab (MEDI 9447) for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (NCT03616886; IJB-SYNERGY-012017; EudraCT2017-004651-23). The randomized, open-label trial intend to enroll approximately 129 patients in Belgium and France^[633]. In December 2021, the company presented data from the trial at the 44th Annual San Antonio Breast Cancer Symposium (SABCS-2021)^[634].

In December 2020, M.D. Anderson Cancer Center in collaboration with National Cancer Institute initiated a phase II trial to evaluate the efficacy of oleclumab and durvalumab [see AdisInsight drug profile800037095] as a combination therapy for the treatment of patients with recurrent, refractory, or metastatic multiple sarcoma (NCT04668300; 2020-0159; NCI-2020-05660). The single group, open label trial intends to recruit approximately 75 patients in USA.
In September 2018, Exelixis in collaboration with University of Kansas Medical Center initiated the phase I CAMILLA trial to evaluate the safety, tolerability and efficacy of cabozantinib [See ADIS Insight Drug profile 800021701] in combination with durvalumab in previously treated patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies (IIT2017Cabozant-DurvaGI; NCT03539822). The open-label trial is enrolling approximately 30 patients in the US^[635]. In May 2020, the company presented the preliminary efficacy and safety data at the 56^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020)^[636].

In May 2018, AIO-Studien-gGmbH and AstraZeneca completed a phase II trial that evaluated the objective response rate of the combination of durvalumab and tremelimumab [see ADIS insight drug profile800020650], in addition with gemcitabine or in addition with gemcitabine and cisplatin, in treatment-naive patients with advanced, unresectable and/or metastatic cholangio- and gallbladder carcinoma (AIO-HEP0117; EudraCT2017-001538-25; NCT03473574). The open label trial was initiated in May 2018 and enrolled 128 patients in Germany^[637].

In February 2018, University of Southern California and National Cancer Institute initiated a phase Ib trial to evaluate the efficacy and safety of guadecitabine and durvalumab, in patients with advanced hepatocellular carcinoma, pancreatic adenocarcinoma, and cholangiocarcinoma/gallbladder cancer (0S16-18; NCI2017-01432; P30CA014089; NCT03257761). Evaluation of the adverse events and tumour response are the defined primary endpoints of the trial. The open label trial intends to enrol approximately 90 patients in the US^[638].

In May 2017, Memorial Sloan Kettering Cancer Center initiated a phase II trial to evaluate the safety and effectiveness of durvalumab with tremelimumab [see AdisInsight drug profile 800020650], in patients with relapsed or refractory germ cell tumours (17-160; NCT03158064). Evaluation of overall response is the defined primary endpoint of the trial. The single arm open label trial intends to enrol approximately 29 patients in the US^[639].

In December 2019, Fondazione IRCCS Istituto Nazionale dei Tumori in collaboration with AstraZeneca terminated the phase II APACHE trial due to loss of accrual. The trial was initiated in February 2017. to evaluate durvalumab, alone or in combination with tremelimumab [see AdisInsight drug profile800020650], in patients with advanced and relapsed germ cell tumours (INT123-16; NCT03081923). The primary endpoint is the modified objective response-rate (mORR = RECIST 1.1 complete or partial response or stable disease +STM reduction > 10%). The open label, randomised trial enrolled 36 patients in Italy^[640]. In June 2018, the company presented efficacy data at the 54^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)^[641]. In September 2019, the company presented the efficacy and safety data from the trial at the 44^th European Society for Medical Oncology Congress (ESMO-2019)^[642].

In May 2022, Grupo Espanol de Tumores Neuroendocrinos completed the DUNE phase II trial to evaluate the safety and efficacy of durvalumab with tremelimumab for the treatment of patients with advanced neuroendocrine tumours (ESR15-11561-61DUNE; EudraCT2016-002858-20; NCT03095274). This prospective, open label, stratified, exploratory trial was initiated in April 2017, and enrolled 123 patients in Spain^[643]. In September 2020, safety and efficacy results from the trial were presented at the 45th European Society for Medical Oncology Congress (ESMO-2020)^[644]. In September 2021, efficacy results from the trial were presented at the 46th European Society for Medical Oncology Congress (ESM0-2021)^[645].

Columbia University plans a phase II trial to evaluate durvalumab and tremelimumab [see AdisInsight drug profile 800020650] as adjuvant therapy for the treatment of patients with resected non-small cell lung cancer (AAAQ8535; NCT03130764). This trial intends to enrol 30 patients in the US^[646].

In January 2017, Memorial Sloan Kettering Cancer Center initiated a phase II trial to assess the safety and efficacy of durvalumab with or without tremelimumab [see AdisInsight drug profile 800020650] in endometrial cancer (16-1491; NCT03015129). The open-label, parallel, randomised trial is recruiting 80 patients in the US^[647]. Interim analysis results from the trial were presented at 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019)^[648].

Azienda Ospedaliero-Universitaria Careggi plans a phase II trial of durvalumab combined with cetuximab and radiotherapy in locally advanced squamous cell carcinoma of the Head and Neck (DUCRO-HN; EudraCT2016-004668-2; NCT03051906). This open-label trial intends to enrol 69 patients^[649].

City of Hope Medical Center and the National Cancer Institute plan to initiate a pilot feasibility study to evaluate the safety and efficacy of tremelimumab plus durvalumab regimen, following radioembolisation in patients with microsatellite stable colorectal cancer that has spread to the liver (16423; NCI-2016-02001; NCT03005002). Approximately 18 adult and elderly subjects will be enrolled in the US^[650].

In February 2017, Breast International Group and UNICANCER initiated the phase II ULTIMATE trial to assess the safety and efficacy of durvalumab combined with exemestane in patients with ER+/Her2- breast cancer eligible for neoadjuvant endocrine therapy and who present CD8+ T cell infiltration after 4-6 weeks exposure to immune-attractant (tremelimumab) (UC-0140/1606; UCBG-105; BIG-106; EudraCT2016-000764-42; NCT02997995). The open-label, single-group trial is enrolling 240 patients in France^[651].

In February 2017, City of Hope Medical Center and the National Cancer Institute initiated a phase I/II trial to determine the maximum tolerated dose (recommended phase II dose, RP2D), safety and anti-tumour activity of durvalumab with or without lenalidomide [see AdisInsight drug profile 800012854] in patients with relapsed or refractory cutaneous T cell lymphoma (mycosis fungoides or Sezary syndrome) or peripheral T cell lymphoma (NCI-2016-02061; 16221; NCT03011814). The open-label, parallel, randomised trial will enrol approximately 62 patients in the US^[652]. In December 2023, company released preliminary data from the trial were presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023)^[653].

In August 2020, Jonsson Comprehensive Cancer Center in collaboration with AstraZeneca initiated a phase II trial to determine the safety of the treatment combination consisting of brachytherapy and tremelimumab or durvalumab [see ADIS insight drug profile[800020650]] for the gynecological malignancies including ovarian, endometrial, or cervical cancer (19-000459; NCT04395079). The randomised, open label trial is designed to enroll approximately 54 patients in the US^[654].

In July 2022, AstraZeneca, in collaboration with Dana-Farber Cancer Institute, terminated a phase I study as the expansion cohort was not open, that was designed to evaluate the safety and effectiveness of durvalumab and tremelimumab [see AdisInsight drug profile 800020650], in combination with radiation therapy as a possible treatment for recurrent or metastatic gynaecological cancer (17-382; NCT03277482). The non-randomised, open-label study was initiated in June 2018, and enrolled 16 patients in the US^[655].

In November 2021, Yonsei University completed a phase II trial of durvalumab (MEDI 4736) and tremelimumab [see ADIS Insight drug profile 800020650] in patients with receptor-positive, hypermutated metastatic breast cancer identified by whole exome sequencing (4-2016-0912; NCT03608865). The open-label study initiated in September 2017 enroled 30 patients in South Korea^[656].

In December 2016, Case Comprehensive Cancer Center initiated a phase Ib trial to assess the safety and efficacy of durvalumab with or without tremelimumab in patients with locally advanced renal cell carcinoma (CASE12815; NCT02762006). The open-label, single-group trial will enrol approximately 54 patients in the US^[657].

In December 2016, French National Cancer Institute and Gustave Roussy initiated the phase I MEDINDUCTION trial to evaluate the efficacy, feasibility and safety of the association of docetaxel, cisplatin, 5-fluorouracil (standard regimen for induction) and durvalumab, and determine the recommended phase II dose of the combination therapy in patients with locally advanced head and neck squamous cell carcinoma (EudraCT2015-004146-25; 2015/2316; NCT02997332). The open-label, single-group trial recruited 36 patients in France^[658].

In February 2017, VentiRx Pharmaceuticals was acquired by Celgene (VentiRx Pharmaceuticals website, February 2017).

In March 2018, Juno Therapeutics was acquired by Celgene^[659].

Labelling information

In July 2019, the US FDA approved the inclusion of overall survival data from the phase III PACIFIC trial in an update to the durvalumab prescribing information for the patients with unresectable, Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT), in the US^[660].

In October 2020, FDA awarded $USD3.2 million for over four years for a phase II trial oral azacytidine plus romidepsin for the treatment of periT-cell lymphoma^[661].

Patent Information

In March 2022, Bristol-Myers Squibb Co. and E.R. Squibb & Sons, LLC filed a lawsuit in US District Court for the District of Delaware against AstraZeneca alleging that AstraZeneca’s marketing of Imfinzi infringes several of their patents^[111].

In February 2022, Ono Pharmaceuticals filed a lawsuit in Tokyo District Court, Civil Division against AstraZeneca alleging that AstraZeneca’s marketing of Imfinzi in Japan infringes several of their patents^[111]

In July 2017, Bristol-Myers Squibb, E.R. Squibb & Sons LLC, Ono Pharmaceutical and Tasuku Honjo filed a patent infringement action relating to AstraZeneca’s commercialisation of durvalumab in the US District Court . A trial has been scheduled for October 2020^[331].

Drug Properties & Chemical Synopsis

Route of administration IV, SC
Formulation Infusion, Injection, unspecified
Class Antineoplastics, Immunotherapies, Monoclonal antibodies
Target Programmed cell death-1 ligand-1; T lymphocyte
Mechanism of Action Programmed cell death-1 ligand-1 inhibitors; T lymphocyte stimulants
WHO ATC code
L01F-F03 (Durvalumab)
EPhMRA code
L1G (Monoclonal Antibody Antineoplastics)
Chemical name Immunoglobulin G1-kappa, anti-(human programmed cell death 1 ligand 1 (B7 homolog 1,CD274)); human monoclonal antibody; γ1 heavy chain (1-451) [human VH (IGHV3-7*01 (99%) –IGHJ4*01) [8.8.14] (1-121) –IGHG1*03 (CH1 (122-219), hinge (220-234), CH2 L4>F(238),L5>E(239),P101>S(335) (235-344), CH3 (345-451)) (122-451)] (224-215')-disulfide with κ light chain (1'-215') [human V-KAPPA (IGKV3-20*01 (97%) –IGKJ1*01) [7.3.9] (1'-108') –IGKC*01(109'-215')] dimer (230-230'':233-233'')-bisdisulfide
Molecular formula C6502 H10018 N1742 O2024 S42
CAS Registry Number 1428935-60-7

Indication	Biomarker Function	Biomarker Name	Number of Trials
acute myeloid leukaemia	Eligibility Criteria	PML-RARA fusion FANCB C-Kit 1 more biomarker names Show less	1 1 1
adenocarcinoma	Arm Group Label	WEE1 PLK4 Microsatellite Instable (MSI) Androgen Receptor (AR) 2 more biomarker names Show less	1 1 1 1
adenocarcinoma	Outcome Measure	Vascular endothelial growth factor A (VEGF) Tumor Mutational Burden tubulin folding cofactor E Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PSA PD-L1/CD274 PD-1/CD279 L-Aspartic acid Interferon Gamma (IFNg) Hydrocortisone HER2/ERBB2 GINS complex subunit 2 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 Epidermal growth factor receptor (EGFR) Creatinine Creatine cleavage and polyadenylation specific factor 4 CD3 gamma chain (CD3G) Cardiac Troponin I Carbohydrate antigen 19-9 (CA 19-9) C-reactive protein (CRP) Bruton's tyrosine kinase (BTK) BRCA2 BRCA1 BNP Bilirubin Ataxia telangiectasia mutated ALT 35 more biomarker names Show less	1 1 1 1 1 1 2 2 3 5 11 2 1 1 1 1 1 1 1 1 1 1 1 2 1 1 2 1 2 1 2 1 1 1 2 1 1
adenocarcinoma	Brief Title	PD-L1/CD274 PD-1/CD279 Neprilysin Microsatellite Stable (MSS) Microsatellite Instable (MSI) KRAS HER2/ERBB2 Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Colony stimulating factor 1 receptor (CSF1R) 8 more biomarker names Show less	4 1 1 2 2 1 1 1 1 1
adenocarcinoma	Arm Group Description	VEGFR PD-L1/CD274 Microsatellite Instable (MSI) Macrophage colony stimulating factor (MCSF) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) Interferon Gamma (IFNg) HER2/ERBB2 Folinic acid Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) Cyclin-dependent kinase 4 (CDK4) cyclin-dependent kinase 12 5'-nucleotidase ecto 14 more biomarker names Show less	1 4 3 1 1 1 2 1 2 1 1 1 1 1 1 1
adenocarcinoma	Detailed Description	Tumor Mutational Burden trophoblast glycoprotein teneurin transmembrane protein 1 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 p63 Microsatellite Stable (MSS) Microsatellite Instable (MSI) KRAS Interferon Gamma (IFNg) Inducible T cell co-stimulator (ICOS) IDH2 IDH1 HER2/ERBB2 Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 cyclin-dependent kinase 12 CD3 gamma chain (CD3G) Carbohydrate antigen 19-9 (CA 19-9) Adenosine diphosphate ribose 25 more biomarker names Show less	1 1 1 2 2 1 11 5 1 3 2 2 1 1 1 1 3 1 1 1 1 2 3 1 2 1 1
adenocarcinoma	Eligibility Criteria	WT1 Vascular endothelial growth factor A (VEGF) UV radiation resistance associated Uridine 5'-diphosphate UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor necrosis factor alpha (TNF-alpha) Tumor Mutational Burden TTF1 trophoblast glycoprotein Thyroxine (T4) Thyroid stimulating hormone beta (TSH) TGFBR1 Testosterone T-cell surface antigen CD4 T-Cell differentiation antigen CD8 succinate dehydrogenase complex, subunit B, iron sulfur (Ip) sideroflexin 1 ROS1 retinal pigment epithelium-specific protein 65kDa RET receptor accessory protein 5 RAS RAD51 paralog D RAD51 paralog C PSA prostaglandin I2 (prostacyclin) receptor (IP) PMS2 phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PD-L2 PD-L1/CD274 PD-1/CD279 partner and localizer of BRCA2 PARP-1 p63 Nuclear protein Ki67 NK2 homeobox 1 Nibrin neuralized E3 ubiquitin protein ligase 1 MSH6 MSH2 MRE11 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Stable (MSS) Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) KRAS Interferon Gamma (IFNg) inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma IDH2 IDH1 HER2/ERBB2 gonadotropin releasing hormone 1 GEN1, Holliday junction 5' flap endonuclease FSH family with sequence similarity 175, member A Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) DPYD DNA (cytosine-5-)-methyltransferase 3 beta discoidin domain receptor tyrosine kinase 1 cytotoxic T-lymphocyte-associated protein 4 cytoskeleton-associated protein 4 Cytokeratin 18 cyclin-dependent kinase 12 Creatinine Creatine collagen, type XI, alpha 2 CHK2 chaperonin containing TCP1 subunit 3 Cardiac Troponin I Butyl nitrite Butanone BRCA2 BRCA1 BRAF ATPase inhibitory factor 1 (ATPI) Ataxia telangiectasia mutated artemin Anaplastic lymphoma receptor tyrosine kinase (ALP) amelogenin, X-linked Alpha-fetoprotein (AFP) Alkaline phosphatase (ALPL) 87 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 1 4 4 1 1 1 4 1 3 1 1 1 1 11 1 2 1 1 10 6 1 1 2 1 1 1 1 2 2 1 2 1 4 7 1 18 3 1 1 1 1 7 1 1 6 1 1 15 4 1 1 3 1 1 1 2 1 1 1 1 1 1 1 2 1 4 1 2 1 10 1 1 1
adenocarcinoma	Official Title	Transforming growth factor-beta (TGF-beta) PD-L1/CD274 PD-1/CD279 PARP-1 Microsatellite Stable (MSS) Microsatellite Instable (MSI) KRAS Human Microbiome HER2/ERBB2 Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Colony stimulating factor 1 receptor (CSF1R) collagen, type XI, alpha 2 Bruton's tyrosine kinase (BTK) 5'-nucleotidase ecto 13 more biomarker names Show less	1 9 1 1 2 1 1 1 1 2 4 1 1 2 1
adenocarcinoma	Brief Summary	PD-L1/CD274 PD-1/CD279 Microsatellite Stable (MSS) Microsatellite Instable (MSI) mannose receptor, C type 1 KRAS Isocitric acid IDH2 IDH1 HER2/ERBB2 Epidermal growth factor receptor (EGFR) 9 more biomarker names Show less	3 1 2 1 2 2 1 1 1 2 2
Adenoid cystic carcinoma	Outcome Measure	PD-1/CD279	1
adenosquamous carcinoma	Brief Title	Neprilysin	1
adenosquamous carcinoma	Outcome Measure	Thyroid stimulating hormone beta (TSH) PD-L1/CD274 L-Aspartic acid Creatinine Bilirubin ALT 4 more biomarker names Show less	1 1 1 1 1 1
adrenal cancer	Eligibility Criteria	CA125 ovarian cancer antigen (MUC16)	1
adrenocortical carcinoma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
adrenocortical carcinoma	Outcome Measure	PD-L1/CD274 PD-1/CD279	1 1
advanced breast cancer	Arm Group Label	Microsatellite Instable (MSI)	1
advanced breast cancer	EligibilityCriteria	trophoblast glycoprotein	1
advanced breast cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) UBE2C tumor protein p53 binding protein 1 transmembrane p24 trafficking protein 7 Thymidylate synthetase TCEAL1 T-Cell differentiation antigen CD8 Survivin Sjogren syndrome/scleroderma autoantigen 1 SERPINA2 RRM2 replication protein A2 Ras protein specific guanine nucleotide releasing factor 1 RAD51 PTTG1 PSA proteasome 26S subunit, non-ATPase 9 PD-L1/CD274 PD-1/CD279 PCNA PARP-1 p53 (tumor protein p53) NUF2 Nuclear protein Ki67 NKG2D (KLRK1) NDC80 mitogen-activated protein kinase 14 methylmalonic aciduria (cobalamin deficiency) cblB type MAPK1 Mab-21 domain containing 1 LAG-3 (CD223) Interferon Gamma (IFNg) HER2/ERBB2 H3P23 FOXP3 Estrogen receptor alpha (ER alpha) dynactin subunit 6 DNA polymerase delta interacting protein 2 discoidin domain receptor tyrosine kinase 1 Cyclin B1 CXCL9 CRK proto-oncogene, adaptor protein collagen, type XI, alpha 2 CEP55 cell division cycle 25C CDKN1B CDC20 Bruton's tyrosine kinase (BTK) BRCA2 BRCA1 ATR Ataxia telangiectasia mutated anthrax toxin receptor 1 activator of HSP90 ATPase activity 1 5'-nucleotidase ecto 53 more biomarker names Show less	1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 9 1 1 1 1 1 2 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 1 1 1 1 1 1
advanced breast cancer	Brief Title	PD-L1/CD274 HER2/ERBB2 Estrogen receptor alpha (ER alpha) cytotoxic T-lymphocyte-associated protein 4 2 more biomarker names Show less	2 8 1 2
advanced breast cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 1 more biomarker names Show less	1 1 2
advanced breast cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) tubulin folding cofactor E trophoblast glycoprotein PGR PD-L1/CD274 PD-1/CD279 Pancreatic lipase HER2/ERBB2 Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) BRCA1 11 more biomarker names Show less	1 1 1 2 4 1 1 6 1 1 1 1 1
advanced breast cancer	Eligibility Criteria	Tumor Mutational Burden tubulin folding cofactor E Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 Serum albumin ROS1 RAS RAD54L RAD51 paralog D RAD51 paralog C RAD51 paralog B protein phosphatase 2 regulatory subunit Balpha Progesterone PGR PD-L1/CD274 PD-1/CD279 partner and localizer of BRCA2 Nuclear protein Ki67 Nibrin neuralized E3 ubiquitin protein ligase 1 MRE11 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) hypertrichosis 2 (generalized, congenital) HER2/ERBB2 glycosylated serum albumin FSH Fanconi anemia, complementation group L FANCA Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 20 CYP3A4 Cyclin-dependent kinase 4 (CDK4) cyclin-dependent kinase 12 CHK2 CHK1 chaperonin containing TCP1 subunit 3 CA125 ovarian cancer antigen (MUC16) Butyl nitrite BRCA2 BRCA1 interacting protein C-terminal helicase 1 BRCA1 associated RING domain 1 BRCA1 BRAF B-lymphocyte antigen CD20 Ataxia telangiectasia mutated artemin Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT 5'-nucleotidase ecto 51 more biomarker names Show less	2 1 2 3 1 1 1 1 1 1 1 1 1 11 5 2 1 1 1 2 1 1 2 7 1 28 1 4 1 1 11 3 1 1 1 1 1 1 1 1 1 1 3 1 1 2 3 1 1 1 2 1 1
advanced breast cancer	Official Title	PD-L1/CD274 PARP-1 Interleukin-23 (IL-23) interleukin 37 HER2/ERBB2 Estrogen receptor alpha (ER alpha) cytotoxic T-lymphocyte-associated protein 4 collagen, type XI, alpha 2 Bruton's tyrosine kinase (BTK) 7 more biomarker names Show less	5 1 1 1 8 1 2 1 2
advanced breast cancer	Brief Summary	Microsatellite Stable (MSS) Microsatellite Instable (MSI) HER2/ERBB2 Estrogen receptor alpha (ER alpha) 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 8 2 1
anal cancer	Outcome Measure	PD-1/CD279	1
anal cancer	Arm Group Description	Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35)	1 1
anal cancer	Detailed Description	PD-L1/CD274	1
anal cancer	Eligibility Criteria	T-cell surface antigen CD4 PSA PD-L1/CD274 1 more biomarker names Show less	3 1 1
anal cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	1 1
appendiceal cancer	Eligibility Criteria	T-cell surface antigen CD4	1
appendiceal cancer	Outcome Measure	PD-1/CD279	1
astrocytoma	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
astrocytoma	Detailed Description	IDH2 IDH1	1 1
astrocytoma	Eligibility Criteria	Inhibin A IDH2 IDH1 Creatinine Alpha-fetoprotein (AFP) 3 more biomarker names Show less	1 1 1 1 1
astrocytoma	Outcome Measure	PD-L1/CD274	1
B-cell lymphoma	Eligibility Criteria	PD-1/CD279 CA125 ovarian cancer antigen (MUC16) c-Myc Bcl-6 B-lymphocyte antigen CD19 B-cell lymphoma 2 (Bcl-2) 4 more biomarker names Show less	1 1 2 2 1 2
B-cell lymphoma	Official Title	PD-L1/CD274 B-lymphocyte antigen CD19	1 1
B-cell lymphoma	Outcome Measure	PD-L1/CD274	2
basal cell cancer	Outcome Measure	PD-1/CD279	1
biliary cancer	Outcome Measure	PD-L1/CD274 Down syndrome chromosome region	1 1
biliary cancer	Brief Title	testis and ovary specific PAZ domain containing 1 ADAM metallopeptidase domain 17	1 1
biliary cancer	Arm Group Description	ADAM metallopeptidase domain 17	2
biliary cancer	Detailed Description	PD-L1/CD274 IDH2 IDH1 betacellulin 2 more biomarker names Show less	1 1 1 1
biliary cancer	Eligibility Criteria	Luteinizing hormone (LH) IDH2 IDH1 FSH CA125 ovarian cancer antigen (MUC16) 3 more biomarker names Show less	4 1 1 2 1
biliary cancer	Official Title	ADAM metallopeptidase domain 17	1
biliary cancer	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
bladder cancer	Arm Group Label	PD-L1/CD274 Microsatellite Instable (MSI) cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	1 1 1
bladder cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) ubiquitin associated and SH3 domain containing B Tumor necrosis factor alpha (TNF-alpha) Transthyretin TERT T-Cell differentiation antigen CD8 RPS6 PD-L1/CD274 PD-1/CD279 MHC class I antigen HLA-A heavy chain (HLA-A) Interleukin-8 (IL-8) Interleukin-6 (IL-6) Interleukin-5 (IL-5) Interleukin-4 (IL-4) Interleukin-2 (IL-2) Interleukin-17 (IL-17) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) Interleukin-10 (IL-10) Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) HLA-A GTP binding protein 1 Granulocyte-macrophage colony-stimulating factor (GM-CSF) glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 Fibroblast growth factor receptor 3 (FGFR3) Fanconi renotubular syndrome Epithelial cell adhesion molecule (EpCAM) enhancer of mRNA decapping 4 cytokine inducible SH2-containing protein CD36 molecule (thrombospondin receptor) c-Met annexin A6 34 more biomarker names Show less	1 1 1 1 1 2 1 10 1 1 1 2 1 1 2 1 2 2 2 2 1 1 1 1 1 1 1 1 2 1 1 1 2 1 1 1
bladder cancer	Brief Title	PD-L1/CD274	1
bladder cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) cytotoxic T-lymphocyte-associated protein 4 Creatinine 2 more biomarker names Show less	1 1 1 1
bladder cancer	Detailed Description	TSC1 trophoblast glycoprotein RPTOR independent companion of MTOR, complex 2 retinoblastoma 1 PD-L1/CD274 PD-1/CD279 p16 mTOR Inducible T cell co-stimulator (ICOS) Fibroblast Growth Factor (FGF2) Cyclin E1 CD80 molecule c-Myc 11 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 1
bladder cancer	Eligibility Criteria	trophoblast glycoprotein T-cell surface antigen CD4 suppressor of cytokine signaling 5 solute carrier organic anion transporter family member 1B3 sideroflexin 1 retinoblastoma 1 PSA PD-L2 PD-L1/CD274 PD-1/CD279 p16 N-Myc MYCL proto-oncogene Microsatellite Instable (MSI) MATE2 MATE1 Luteinizing hormone (LH) HER2/ERBB2 FSH Fibroblast growth factor receptor 3 (FGFR3) cytotoxic T-lymphocyte-associated protein 4 cytokine inducible SH2-containing protein Cyclin E1 c-Myc Alkaline phosphatase (ALPL) 23 more biomarker names Show less	1 1 1 1 1 1 7 2 3 2 1 1 1 1 1 1 13 1 1 1 3 2 1 1 1
bladder cancer	Official Title	XPA binding protein 2 Transforming growth factor-beta (TGF-beta) PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 crooked neck pre-mRNA splicing factor 1 3 more biomarker names Show less	1 1 1 3 1
bladder cancer	Brief Summary	cytokine inducible SH2-containing protein	1
brain metastases	Outcome Measure	PD-L1/CD274 L-Tryptophan Kynurenine Indoleamine 2, 3-dioxygenase 1 (IDO1) D-Tryptophan c-Met 4 more biomarker names Show less	2 1 1 1 1 1
brain metastases	Detailed Description	Tumor Mutational Burden TERT T-Cell differentiation antigen CD8 schlafen family member 11 PD-L1/CD274 IDH2 IDH1 Cholangitis, primary sclerosing Chemokine IFN-Î³-inducible protein 10 (IP-10/CXCL10) C-C motif chemokine 5 (CCL5 8 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1
brain metastases	Eligibility Criteria	PD-L2 PD-L1/CD274 PD-1/CD279 Luteinizing hormone (LH) LOC102724197 IDH2 IDH1 HER2/ERBB2 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase light chain 1 gamma-glutamyltransferase 2 FSH Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Anaplastic lymphoma receptor tyrosine kinase (ALP) 16 more biomarker names Show less	1 3 3 7 1 1 1 1 1 1 1 1 1 1 2 2 3 2
brain metastases	Official Title	collagen, type XI, alpha 2	1
brain metastases	Brief Summary	Isocitric acid IDH2 IDH1 Cholangitis, primary sclerosing 2 more biomarker names Show less	1 1 1 1
breast cancer	Eligibility Criteria	Luteinizing hormone (LH) FSH cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	1 1 1
breast cancer	Outcome Measure	PD-L1/CD274	1
cancer	Arm Group Description	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	1 1
cancer	Arm Group Label	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	1 1
cancer	Brief Title	Human Microbiome	1
cancer	Official Title	Human Microbiome	1
cancer metastases	Eligibility Criteria	hypertrichosis 2 (generalized, congenital)	1
carcinoid tumour	Eligibility Criteria	somatostatin Nuclear protein Ki67	1 1
carcinoid tumour	Outcome Measure	Neuron-specific enolase (NSE)	1
carcinoma	Arm Group Label	Microsatellite Instable (MSI)	1
carcinoma	Outcome Measure	Vascular endothelial growth factor A (VEGF) Tumor Mutational Burden Transthyretin T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PSA PD-L1/CD274 PD-1/CD279 p16 Nuclear protein Ki67 Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) H3P10 GTP binding protein 1 glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 FOXP3 Fanconi renotubular syndrome Epithelial cell adhesion molecule (EpCAM) Epidermal growth factor receptor (EGFR) enhancer of mRNA decapping 4 cytokine inducible SH2-containing protein Cytokeratin 20 Creatinine CD38 CD36 molecule (thrombospondin receptor) CD3 gamma chain (CD3G) CA125 ovarian cancer antigen (MUC16) c-Met B-lymphocyte antigen CD20 Anaplastic lymphoma receptor tyrosine kinase (ALP) 33 more biomarker names Show less	1 1 1 1 1 1 3 1 20 3 2 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 1 1
carcinoma	Brief Title	PD-L1/CD274 iroquois homeobox 2 HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 BRCA2 BRCA1 ARID1A ADAM metallopeptidase domain 17 6 more biomarker names Show less	2 1 1 1 1 1 1 2
carcinoma	Arm Group Description	Microsatellite Instable (MSI) iroquois homeobox 2 Creatinine ARID1A ADAM metallopeptidase domain 17 3 more biomarker names Show less	1 1 1 1 2
carcinoma	Detailed Description	Tumor Mutational Burden tubulin folding cofactor E T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PD-1/CD279 p16 mannose receptor, C type 1 Inducible T cell co-stimulator (ICOS) H3P10 FOXP3 Cholangitis, primary sclerosing CD80 molecule CD3 gamma chain (CD3G) BRCA2 BRCA1 ARID1A 18 more biomarker names Show less	1 2 1 1 1 2 1 8 1 2 1 1 2 1 1 1 1 1 1 1
carcinoma	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 suppressor of cytokine signaling 5 succinate dehydrogenase complex, subunit B, iron sulfur (Ip) ROS1 RAS PSA protein phosphatase 2, regulatory subunit A, alpha prostaglandin I2 (prostacyclin) receptor (IP) polymerase (DNA directed), delta 1, catalytic subunit PMS2 PMS1 phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PGR PD-L1/CD274 PD-1/CD279 p16 Nuclear protein Ki67 MSH6 MSH3 MSH2 MLH3 MLH1 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) L-Aspartic acid inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma HER2/ERBB2 H3P10 FSH Ethenyl acetate Estrogen receptor alpha (ER alpha) Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) DNA polymerase delta 2, accessory subunit cytotoxic T-lymphocyte-associated protein 4 cytokine inducible SH2-containing protein Cytokeratin 20 CYP3A4 Cyclin-dependent kinase 4 (CDK4) Creatine CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 BRAF Bilirubin B-lymphocyte antigen CD20 ATPase inhibitory factor 1 (ATPI) Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Alkaline phosphatase (ALPL) Adenosine diphosphate ribose 60 more biomarker names Show less	2 2 2 2 2 2 2 2 1 1 1 1 1 6 1 1 1 1 1 1 1 14 1 3 2 1 1 1 1 1 1 2 27 1 1 5 3 3 1 1 2 3 1 1 2 1 1 1 1 2 2 2 1 1 1 1 1 2 2 1 2 1
carcinoma	Official Title	XPA binding protein 2 Transforming growth factor-beta (TGF-beta) PD-L1/CD274 iroquois homeobox 2 Interleukin-23 (IL-23) interleukin 37 HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 crooked neck pre-mRNA splicing factor 1 BRCA2 BRCA1 ARID1A ADAM metallopeptidase domain 17 11 more biomarker names Show less	1 1 4 1 1 1 2 3 1 1 1 1 1
carcinoma	Brief Summary	T-Cell differentiation antigen CD8 PD-L1/CD274 Microsatellite Stable (MSS) HER2/ERBB2 Estrogen receptor alpha (ER alpha) cytokine inducible SH2-containing protein Cholangitis, primary sclerosing BRCA2 BRCA1 7 more biomarker names Show less	1 1 1 2 1 1 1 1 1
cervical cancer	Outcome Measure	Tumor Mutational Burden Thyroid stimulating hormone beta (TSH) PD-L1/CD274 PD-1/CD279 L-Aspartic acid FOXP3 Creatinine Bilirubin ALT 7 more biomarker names Show less	1 1 2 1 1 1 1 1 1
cervical cancer	Brief Title	Neprilysin cytotoxic T-lymphocyte-associated protein 4	1 1
cervical cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) 2 more biomarker names Show less	1 1 1 1
cervical cancer	Detailed Description	trophoblast glycoprotein PD-L1/CD274 PD-1/CD279 Pancreatic lipase 2 more biomarker names Show less	1 2 1 1
cervical cancer	Eligibility Criteria	trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 Serum albumin PSA PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Luteinizing hormone (LH) HER2/ERBB2 glycosylated serum albumin Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 18 Butanone BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) 16 more biomarker names Show less	1 1 1 1 1 4 3 1 1 5 2 1 1 2 1 1 1 1
cervical cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	2 2
cholangiocarcinoma	Outcome Measure	T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PD-L2 PD-L1/CD274 PD-1/CD279 MMP9 matrix metallopeptidase 7 Macrophage antigen CD68 lymphocyte antigen 75 LY75-CD302 readthrough immunoglobulin heavy constant mu FOXP3 Down syndrome chromosome region CXCL9 CXCL13 Chemokine IFN-Î³-inducible protein 10 (IP-10/CXCL10) CD3 gamma chain (CD3G) 17 more biomarker names Show less	1 1 1 1 1 2 2 1 1 1 1 1 1 1 1 1 1 1 1
cholangiocarcinoma	OutcomeMeasure	SMAD4	1
cholangiocarcinoma	Brief Title	testis and ovary specific PAZ domain containing 1 Colony stimulating factor 1 receptor (CSF1R)	1 1
cholangiocarcinoma	Arm Group Description	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 ADAM metallopeptidase domain 17 1 more biomarker names Show less	1 1 1
cholangiocarcinoma	Detailed Description	PD-L1/CD274 PD-1/CD279 IDH2 IDH1 betacellulin 3 more biomarker names Show less	2 1 1 1 1
cholangiocarcinoma	Eligibility Criteria	PSA Luteinizing hormone (LH) IDH2 IDH1 FSH CA125 ovarian cancer antigen (MUC16) Bilirubin amelogenin, X-linked 6 more biomarker names Show less	1 6 1 1 2 1 1 1
cholangiocarcinoma	Official Title	Colony stimulating factor 1 receptor (CSF1R)	1
cholangiocarcinoma	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
chronic lymphocytic leukaemia	Official Title	PD-L1/CD274	1
chronic lymphocytic leukaemia	Outcome Measure	PD-L1/CD274	1
clear cell sarcoma	Eligibility Criteria	Luteinizing hormone (LH)	1
CNS cancer	Eligibility Criteria	Luteinizing hormone (LH)	1
colon cancer	Brief Summary	Microsatellite Instable (MSI) mannose receptor, C type 1	1 1
colon cancer	Brief Title	Microsatellite Instable (MSI)	1
colon cancer	Eligibility Criteria	T-cell surface antigen CD4 receptor accessory protein 5 PMS2 MSH6 MSH2 MLH1 4 more biomarker names Show less	1 1 1 1 1 1
colon cancer	Official Title	cytotoxic T-lymphocyte-associated protein 4	1
colorectal cancer	Arm Group Label	Microsatellite Instable (MSI)	1
colorectal cancer	Outcome Measure	T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 SMAD4 PSA PD-L1/CD274 PD-1/CD279 Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) CD3 gamma chain (CD3G) 10 more biomarker names Show less	1 1 1 4 2 1 1 6 1 1 1 1
colorectal cancer	Brief Title	PD-L1/CD274 Microsatellite Stable (MSS) cytotoxic T-lymphocyte-associated protein 4 Colony stimulating factor 1 receptor (CSF1R) 2 more biomarker names Show less	4 5 1 1
colorectal cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) Macrophage colony stimulating factor (MCSF) Interferon Gamma (IFNg) 2 more biomarker names Show less	1 2 1 1
colorectal cancer	Detailed Description	Tumor Mutational Burden T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PD-L1/CD274 PD-1/CD279 p63 Microsatellite Stable (MSS) KRAS Interferon Gamma (IFNg) CD3 gamma chain (CD3G) Adenosine diphosphate ribose 11 more biomarker names Show less	1 1 1 1 1 5 2 1 4 1 1 1 1
colorectal cancer	Eligibility Criteria	Vascular endothelial growth factor A (VEGF) Tumor Mutational Burden Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 RAS PSA PMS2 PD-L1/CD274 PD-1/CD279 p63 neuralized E3 ubiquitin protein ligase 1 MSH6 MSH2 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Stable (MSS) Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) KRAS Interferon Gamma (IFNg) HER2/ERBB2 Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) discoidin domain receptor tyrosine kinase 1 cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 18 Creatinine Cardiac Troponin I CA125 ovarian cancer antigen (MUC16) Butanone BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) 33 more biomarker names Show less	2 1 1 1 3 2 2 3 3 1 1 2 2 2 1 5 7 1 7 3 1 3 1 7 1 2 1 2 1 1 1 1 1 4 3
colorectal cancer	Official Title	STAT3 PD-L1/CD274 Microsatellite Stable (MSS) cytotoxic T-lymphocyte-associated protein 4 Colony stimulating factor 1 receptor (CSF1R) 3 more biomarker names Show less	1 7 6 4 1
colorectal cancer	Brief Summary	PD-L1/CD274 PD-1/CD279 Microsatellite Stable (MSS) KRAS HER2/ERBB2 Estrogen receptor alpha (ER alpha) 4 more biomarker names Show less	1 1 8 1 1 1
cutaneous T-cell lymphoma	Detailed Description	T-cell surface antigen CD4	1
cutaneous T-cell lymphoma	Eligibility Criteria	TSPYL2	1
diffuse intrinsic pontine glioma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
diffuse intrinsic pontine glioma	Outcome Measure	PD-L1/CD274	1
diffuse large B cell lymphoma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 Luteinizing hormone (LH) Cytokeratin 20 c-Myc BRAF Bcl-6 B-lymphocyte antigen CD20 B-lymphocyte antigen CD19 B-cell lymphoma 2 (Bcl-2) 8 more biomarker names Show less	1 2 1 3 2 1 2 3 2 2
diffuse large B cell lymphoma	Official Title	PD-L1/CD274 Interleukin-23 (IL-23) interleukin 37 Bruton's tyrosine kinase (BTK) B-lymphocyte antigen CD19 3 more biomarker names Show less	1 1 1 1 1
diffuse large B cell lymphoma	Outcome Measure	T-Cell differentiation antigen CD8 STAT3 PD-L1/CD274 Interferon Gamma (IFNg) Bruton's tyrosine kinase (BTK) 3 more biomarker names Show less	1 1 5 1 1
ductal carcinoma	Brief Title	KRAS	1
ductal carcinoma	Arm Group Description	HER2/ERBB2 Folinic acid	1 1
ductal carcinoma	Detailed Description	KRAS	1
ductal carcinoma	Eligibility Criteria	neuralized E3 ubiquitin protein ligase 1 Luteinizing hormone (LH) KRAS HER2/ERBB2 FSH Epidermal growth factor receptor (EGFR) DPYD cytotoxic T-lymphocyte-associated protein 4 6 more biomarker names Show less	1 1 1 1 1 1 1 1
ductal carcinoma	Official Title	KRAS	1
ductal carcinoma	Brief Summary	KRAS	1
dysgerminoma	Eligibility Criteria	PSA Luteinizing hormone (LH) hypertrichosis 2 (generalized, congenital) chorionic gonadotropin beta subunit 5 CGA Alpha-fetoprotein (AFP) 4 more biomarker names Show less	1 1 1 1 1 1
early breast cancer	Outcome Measure	UBE2C tumor protein p53 binding protein 1 transmembrane p24 trafficking protein 7 Thymidylate synthetase TCEAL1 T-Cell differentiation antigen CD8 Survivin Sjogren syndrome/scleroderma autoantigen 1 SERPINA2 RRM2 replication protein A2 Ras protein specific guanine nucleotide releasing factor 1 RAD51 PTTG1 proteasome 26S subunit, non-ATPase 9 PD-L1/CD274 PD-1/CD279 PCNA PARP-1 p53 (tumor protein p53) NUF2 Nuclear protein Ki67 NKG2D (KLRK1) NDC80 mitogen-activated protein kinase 14 methylmalonic aciduria (cobalamin deficiency) cblB type MAPK1 Mab-21 domain containing 1 LAG-3 (CD223) Interferon Gamma (IFNg) HER2/ERBB2 H3P23 Estrogen receptor alpha (ER alpha) dynactin subunit 6 discoidin domain receptor tyrosine kinase 1 Cyclin B1 CXCL9 CRK proto-oncogene, adaptor protein collagen, type XI, alpha 2 CEP55 cell division cycle 25C CDKN1B CDC20 BRCA2 ATR anthrax toxin receptor 1 activator of HSP90 ATPase activity 1 45 more biomarker names Show less	1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 4 1 1 1 1 1 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
early breast cancer	OutcomeMeasure	DNA polymerase delta interacting protein 2	1
early breast cancer	Brief Title	PD-L1/CD274 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 1 more biomarker names Show less	1 3 2
early breast cancer	Arm Group Description	HER2/ERBB2 5'-nucleotidase ecto	1 1
early breast cancer	Detailed Description	T-Cell differentiation antigen CD8 PGR PD-L1/CD274 HER2/ERBB2 Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) Cyclin-dependent kinase 4 (CDK4) 5 more biomarker names Show less	1 1 1 3 1 1 1
early breast cancer	Eligibility Criteria	Thyroid stimulating hormone beta (TSH) T-Cell differentiation antigen CD8 Progesterone PGR PD-L1/CD274 Nuclear protein Ki67 neuralized E3 ubiquitin protein ligase 1 Luteinizing hormone (LH) HER2/ERBB2 FSH Estrogen receptor alpha (ER alpha) Estradiol-17beta 3-sulfate cytokine inducible SH2-containing protein CYP3A4 ALT 13 more biomarker names Show less	1 1 1 5 2 4 1 3 12 2 6 1 1 1 1
early breast cancer	Official Title	PD-L1/CD274 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 1 more biomarker names Show less	1 3 2
early breast cancer	Brief Summary	T-Cell differentiation antigen CD8 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 1 more biomarker names Show less	1 3 1
endometrial cancer	Arm Group Label	PARP-1	1
endometrial cancer	Outcome Measure	T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 SET binding protein 1 PSA PD-L1/CD274 PD-1/CD279 Monocyte differentiation antigen CD14 Macrophage antigen CD68 LAG-3 (CD223) KLRC1 integrin subunit alpha E cytotoxic T-lymphocyte-associated protein 4 CD33 molecule CD3 gamma chain (CD3G) CD163 CD161 (NKRP1) 16 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
endometrial cancer	Arm Group Description	ARID1A	1
endometrial cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) trophoblast glycoprotein PD-L1/CD274 PD-1/CD279 Pancreatic lipase BRCA1 4 more biomarker names Show less	1 1 1 1 1 1
endometrial cancer	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 trophoblast glycoprotein Thyroxine (T4) Thyroid stimulating hormone beta (TSH) succinate dehydrogenase complex, subunit B, iron sulfur (Ip) ROS1 PSA prostaglandin I2 (prostacyclin) receptor (IP) PD-L1/CD274 Microsatellite Instable (MSI) Luteinizing hormone (LH) inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma HER2/ERBB2 FSH Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 BRAF Bilirubin ATPase inhibitory factor 1 (ATPI) Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT 29 more biomarker names Show less	1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 5 1 1 1 2 1 2 1 1 1 1 1 1 1 1 2
endometrial cancer	Official Title	PD-L1/CD274	1
ependymoma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
ependymoma	Outcome Measure	PD-L1/CD274	1
fallopian tube cancer	Outcome Measure	tubulin folding cofactor E PSA PD-L1/CD274 PD-1/CD279 GINS complex subunit 2 CA125 ovarian cancer antigen (MUC16) 4 more biomarker names Show less	1 1 3 1 1 2
fallopian tube cancer	Brief Title	PD-L1/CD274 BRCA2 BRCA1 1 more biomarker names Show less	2 1 1
fallopian tube cancer	Arm Group Description	Granulocyte-macrophage colony-stimulating factor (GM-CSF)	1
fallopian tube cancer	Detailed Description	tubulin folding cofactor E T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PD-1/CD279 Pancreatic lipase mannose receptor, C type 1 FOXP3 CD3 gamma chain (CD3G) BRCA2 BRCA1 12 more biomarker names Show less	2 1 1 1 1 1 3 1 1 1 1 1 1 1
fallopian tube cancer	Eligibility Criteria	Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PARP-1 Luteinizing hormone (LH) HER2/ERBB2 FSH Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 CYP3A4 collagen, type XI, alpha 2 CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Adenosine diphosphate ribose 19 more biomarker names Show less	1 2 1 1 3 1 8 1 3 1 1 1 1 1 3 4 3 1 1 2 1
fallopian tube cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 BRCA2 BRCA1 2 more biomarker names Show less	2 1 1 1
fallopian tube cancer	Brief Summary	BRCA2 BRCA1	1 1
follicular lymphoma	Eligibility Criteria	Cytokeratin 20 c-Myc Bcl-6 B-lymphocyte antigen CD20 B-lymphocyte antigen CD19 B-cell lymphoma 2 (Bcl-2) 4 more biomarker names Show less	1 1 1 1 1 1
follicular lymphoma	Official Title	PD-L1/CD274 Bruton's tyrosine kinase (BTK)	1 1
follicular lymphoma	Outcome Measure	PD-L1/CD274 Bruton's tyrosine kinase (BTK)	2 1
gallbladder cancer	Outcome Measure	PD-L1/CD274 PD-1/CD279 Down syndrome chromosome region 1 more biomarker names Show less	1 1 1
gallbladder cancer	Brief Title	testis and ovary specific PAZ domain containing 1	1
gallbladder cancer	Arm Group Description	ADAM metallopeptidase domain 17	1
gallbladder cancer	Detailed Description	PD-L1/CD274 PD-1/CD279 betacellulin 1 more biomarker names Show less	2 1 1
gallbladder cancer	Eligibility Criteria	PSA Luteinizing hormone (LH) FSH amelogenin, X-linked 2 more biomarker names Show less	1 4 2 1
gastric cancer	Arm Group Label	Microsatellite Instable (MSI)	1
gastric cancer	ArmGroup Description	PD-L1/CD274	2
gastric cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) T-Cell differentiation antigen CD8 STAT3 SMAD4 PD-L1/CD274 Interferon Gamma (IFNg) HER2/ERBB2 FOXP3 BRCA2 BRCA1 Ataxia telangiectasia mutated 9 more biomarker names Show less	1 1 1 1 4 1 1 1 1 1 1
gastric cancer	Brief Title	PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 2 more biomarker names Show less	1 1 1 1
gastric cancer	Arm Group Description	Microsatellite Instable (MSI) Interferon Gamma (IFNg) Folinic acid 1 more biomarker names Show less	2 1 1
gastric cancer	Detailed Description	teneurin transmembrane protein 1 PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 7 more biomarker names Show less	1 1 1 3 1 1 1 1 2
gastric cancer	Eligibility Criteria	Uridine 5'-diphosphate UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor Mutational Burden TGFBR1 Serum albumin polymerase (DNA directed), delta 1, catalytic subunit PMS2 PMS1 PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 MSH6 MSH3 MSH2 MLH3 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Stable (MSS) Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) HER2/ERBB2 glycosylated serum albumin FSH Epidermal growth factor receptor (EGFR) DPYD DNA polymerase delta 2, accessory subunit Cytokeratin 18 Butanone BRAF Ataxia telangiectasia mutated Anaplastic lymphoma receptor tyrosine kinase (ALP) Alpha-fetoprotein (AFP) 36 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 1 1 1 1 1 1 1 1 5 1 2 4 1 1 2 1 1 1 1 1 1 1 1
gastric cancer	Official Title	PD-L1/CD274 PARP-1 Microsatellite Instable (MSI) HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 collagen, type XI, alpha 2 4 more biomarker names Show less	2 1 1 1 1 1
gastric cancer	Brief Summary	PD-L1/CD274 mannose receptor, C type 1 HER2/ERBB2 1 more biomarker names Show less	1 1 2
gastrointestinal cancer	Eligibility Criteria	Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) Epidermal growth factor receptor (EGFR) Alpha-fetoprotein (AFP) 3 more biomarker names Show less	1 1 1 1 1
gastrointestinal cancer	Outcome Measure	STAT3 SMAD4	1 1
gastrointestinal stromal tumours	Eligibility Criteria	somatostatin Nuclear protein Ki67	1 1
gastrointestinal stromal tumours	Outcome Measure	Neuron-specific enolase (NSE)	1
germ cell cancer	Brief Summary	PD-L1/CD274	1
germ cell cancer	Eligibility Criteria	PSA PD-L1/CD274 Luteinizing hormone (LH) hypertrichosis 2 (generalized, congenital) chorionic gonadotropin beta subunit 5 CGA Alpha-fetoprotein (AFP) 5 more biomarker names Show less	1 1 1 1 1 1 1
germ cell cancer	Official Title	PD-L1/CD274	1
giant cell tumours	Eligibility Criteria	Luteinizing hormone (LH)	1
glandular and epithelial neoplasms	Eligibility Criteria	Luteinizing hormone (LH)	1
glioblastoma	Arm Group Label	Microsatellite Instable (MSI)	1
glioblastoma	Outcome Measure	PD-L1/CD274	3
glioblastoma	Arm Group Description	Microsatellite Instable (MSI) MGMT	1 1
glioblastoma	Detailed Description	PD-L1/CD274 IDH2 IDH1 1 more biomarker names Show less	1 1 1
glioblastoma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 Inhibin A IDH2 IDH1 cytotoxic T-lymphocyte-associated protein 4 Creatinine CA125 ovarian cancer antigen (MUC16) Alpha-fetoprotein (AFP) 7 more biomarker names Show less	1 1 1 1 1 1 1 1 1
glioblastoma	Official Title	PD-L1/CD274	1
glioblastoma	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
glioma	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
glioma	Detailed Description	PD-L1/CD274 IDH2 IDH1 1 more biomarker names Show less	1 1 1
glioma	Eligibility Criteria	IDH2 IDH1	1 1
glioma	Outcome Measure	PD-L1/CD274	1
gynaecological cancer	Eligibility Criteria	Luteinizing hormone (LH)	2
haemangiosarcoma	Detailed Description	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 1 1 1
haemangiosarcoma	Eligibility Criteria	Luteinizing hormone (LH)	1
haemangiosarcoma	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 1 1 1
head and neck cancer	Arm Group Label	PD-L1/CD274 Microsatellite Instable (MSI) cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	3 1 1
head and neck cancer	Outcome Measure	T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PD-L1/CD274 PD-1/CD279 p16 long intergenic non-protein coding RNA 1194 Interleukin-6 (IL-6) Interleukin-10 (IL-10) H3P10 FOXP3 Cytokeratin 20 CD38 CD3 gamma chain (CD3G) B-lymphocyte antigen CD20 15 more biomarker names Show less	1 1 1 3 1 10 1 2 1 1 1 2 2 1 1 1 1
head and neck cancer	Brief Title	PD-L1/CD274 iroquois homeobox 2 cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	2 1 2
head and neck cancer	Arm Group Description	VEGFR1 VEGFR RET PDGFRB PDGFRA PD-L1/CD274 Microsatellite Instable (MSI) iroquois homeobox 2 Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) CDK6 CD80 molecule CD177 molecule 12 more biomarker names Show less	1 1 1 1 1 3 2 1 1 2 1 1 1 1
head and neck cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) tubulin folding cofactor E trophoblast glycoprotein T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 cytotoxic T-lymphocyte-associated protein 4 BRCA1 7 more biomarker names Show less	1 1 1 2 8 3 3 1 1
head and neck cancer	Eligibility Criteria	Tumor Mutational Burden tubulin folding cofactor E trophoblast glycoprotein T-Cell differentiation antigen CD8 Serum albumin ROS1 PSA PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 PD-1/CD279 p16 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) Luteinizing hormone (LH) Insulin HER2/ERBB2 H3P10 glycosylated serum albumin Fibroblast growth factor receptor 1 (FGFR1) Ethenyl acetate Epidermal growth factor receptor (EGFR) DPYD cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 20 Cytokeratin 18 Cystatin C Cyclin-dependent kinase 4 (CDK4) Creatinine Butanone BRCA2 BRAF B-lymphocyte antigen CD20 Anaplastic lymphoma receptor tyrosine kinase (ALP) 35 more biomarker names Show less	1 1 1 1 1 1 3 1 1 1 1 12 3 10 1 1 1 9 1 3 10 1 1 1 3 1 1 1 1 1 1 1 1 1 3 1 2
head and neck cancer	Official Title	PD-L1/CD274 iroquois homeobox 2 Interleukin-23 (IL-23) interleukin 37 cytotoxic T-lymphocyte-associated protein 4 3 more biomarker names Show less	4 1 1 1 4
head and neck cancer	Brief Summary	PD-L1/CD274 p16 H3P10 1 more biomarker names Show less	1 1 1
hepatoblastoma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
hepatoblastoma	Outcome Measure	PD-L1/CD274	1
hER2 negative breast cancer	Outcome Measure	PD-L1/CD274 PD-1/CD279 Nuclear protein Ki67 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 3 more biomarker names Show less	2 1 1 2 1
hER2 negative breast cancer	Brief Title	PD-L1/CD274 HER2/ERBB2	1 6
hER2 negative breast cancer	Arm Group Description	PD-L1/CD274 HER2/ERBB2	1 1
hER2 negative breast cancer	Detailed Description	PD-L1/CD274 HER2/ERBB2 Epidermal growth factor receptor (EGFR) 1 more biomarker names Show less	1 2 1
hER2 negative breast cancer	Eligibility Criteria	RAS RAD54L RAD51 paralog D RAD51 paralog C RAD51 paralog B protein phosphatase 2 regulatory subunit Balpha PGR PD-L1/CD274 partner and localizer of BRCA2 Nuclear protein Ki67 Nibrin neuralized E3 ubiquitin protein ligase 1 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) HER2/ERBB2 FSH Fanconi anemia, complementation group L FANCA Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) Cyclin-dependent kinase 4 (CDK4) cyclin-dependent kinase 12 CHK2 CHK1 Butyl nitrite BRCA2 BRCA1 interacting protein C-terminal helicase 1 BRCA1 associated RING domain 1 BRCA1 Ataxia telangiectasia mutated artemin 30 more biomarker names Show less	1 1 1 1 1 1 2 1 1 2 1 1 1 1 1 12 2 1 1 3 1 1 1 1 1 1 1 1 1 1 1 1
hER2 negative breast cancer	Official Title	PD-L1/CD274 HER2/ERBB2	3 6
hER2 negative breast cancer	Brief Summary	Microsatellite Stable (MSS) Microsatellite Instable (MSI) HER2/ERBB2 Estrogen receptor alpha (ER alpha) 2 more biomarker names Show less	1 1 5 1
hER2 negative breastcancer	Eligibility Criteria	MRE11	1
hER2 positive breast cancer	Outcome Measure	PD-L1/CD274 5'-nucleotidase ecto	1 1
hER2 positive breast cancer	Brief Title	HER2/ERBB2	1
hER2 positive breast cancer	Arm Group Description	HER2/ERBB2	1
hER2 positive breast cancer	Detailed Description	HER2/ERBB2	1
hER2 positive breast cancer	Eligibility Criteria	PGR PD-L1/CD274 neuralized E3 ubiquitin protein ligase 1 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 5'-nucleotidase ecto 4 more biomarker names Show less	2 1 1 3 1 1
hER2 positive breast cancer	Official Title	HER2/ERBB2	1
hER2 positive breast cancer	Brief Summary	HER2/ERBB2 5'-nucleotidase ecto	1 1
Hodgkin's disease	Official Title	PD-L1/CD274	1
Hodgkin's disease	Outcome Measure	PD-L1/CD274	1
Hypopharyngeal cancer	Outcome Measure	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 2 more biomarker names Show less	1 3 1 1
Hypopharyngeal cancer	Brief Title	iroquois homeobox 2	1
Hypopharyngeal cancer	Arm Group Description	iroquois homeobox 2	1
Hypopharyngeal cancer	Detailed Description	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 cytotoxic T-lymphocyte-associated protein 4 3 more biomarker names Show less	1 3 2 2 1
Hypopharyngeal cancer	Eligibility Criteria	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 Luteinizing hormone (LH) H3P10 DPYD Cystatin C Creatinine 6 more biomarker names Show less	1 3 3 3 3 1 1 1
Hypopharyngeal cancer	Official Title	iroquois homeobox 2	1
large cell carcinoma	Eligibility Criteria	PD-L1/CD274 FSH Alpha-fetoprotein (AFP) 1 more biomarker names Show less	2 1 1
large cell carcinoma	Official Title	PD-L1/CD274	1
laryngeal cancer	Outcome Measure	T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 FOXP3 Cytokeratin 20 CD38 CD3 gamma chain (CD3G) B-lymphocyte antigen CD20 10 more biomarker names Show less	1 1 1 2 4 2 2 1 1 1 1 1
laryngeal cancer	Brief Title	iroquois homeobox 2	1
laryngeal cancer	Arm Group Description	iroquois homeobox 2	1
laryngeal cancer	Detailed Description	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 cytotoxic T-lymphocyte-associated protein 4 3 more biomarker names Show less	1 3 2 2 1
laryngeal cancer	Eligibility Criteria	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 Luteinizing hormone (LH) H3P10 DPYD Cystatin C Creatinine 6 more biomarker names Show less	1 4 4 5 4 1 1 1
laryngeal cancer	Official Title	iroquois homeobox 2	1
leiomyosarcoma	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8	1 1
leiomyosarcoma	Brief Title	PD-L1/CD274	1
leiomyosarcoma	Detailed Description	PD-L1/CD274 p63 Adenosine diphosphate ribose 1 more biomarker names Show less	1 1 1
leiomyosarcoma	Eligibility Criteria	Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 p63 MXLPO discoidin domain receptor tyrosine kinase 1 amelogenin, X-linked 4 more biomarker names Show less	1 1 1 1 1 1
leiomyosarcoma	Official Title	PD-L1/CD274	1
liposarcoma	Detailed Description	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 1 1 1
liposarcoma	Eligibility Criteria	MXLPO Luteinizing hormone (LH) amelogenin, X-linked 1 more biomarker names Show less	1 1 1
liposarcoma	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 1 1 1
liver cancer	Arm Group Label	Microsatellite Instable (MSI) ADAM metallopeptidase domain 17	1 1
liver cancer	Outcome Measure	Tumor Mutational Burden T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PD-L2 PD-L1/CD274 PD-1/CD279 MMP9 matrix metallopeptidase 7 Macrophage antigen CD68 lymphocyte antigen 75 LY75-CD302 readthrough IVD immunoglobulin heavy constant mu FOXP3 CXCL9 CXCL13 Chemokine IFN-Î³-inducible protein 10 (IP-10/CXCL10) CD3 gamma chain (CD3G) Alpha-fetoprotein (AFP) 18 more biomarker names Show less	1 1 1 1 1 5 3 1 1 1 1 1 1 1 1 1 1 1 1 1
liver cancer	Brief Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 ADAM metallopeptidase domain 17 1 more biomarker names Show less	1 1 6
liver cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) ADAM metallopeptidase domain 17 1 more biomarker names Show less	1 2 5
liver cancer	Detailed Description	Tumor Mutational Burden trophoblast glycoprotein PD-L1/CD274 PD-1/CD279 Alpha-fetoprotein (AFP) 3 more biomarker names Show less	1 1 3 1 1
liver cancer	Eligibility Criteria	trophoblast glycoprotein T-cell surface antigen CD4 ROS1 PSA PD-L2 PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) HER2/ERBB2 Epidermal growth factor receptor (EGFR) Cytokeratin 18 Butanone BRAF Bilirubin Anaplastic lymphoma receptor tyrosine kinase (ALP) Alpha-fetoprotein (AFP) 18 more biomarker names Show less	1 1 1 1 1 1 2 1 1 1 1 4 2 3 1 1 2 1 2 2
liver cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 ADAM metallopeptidase domain 17 1 more biomarker names Show less	2 1 5
liver cancer	Brief Summary	PD-L1/CD274	2
liver metastases	Outcome Measure	T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 CD3 gamma chain (CD3G) 4 more biomarker names Show less	1 1 2 1 1 1
liver metastases	Brief Title	Microsatellite Stable (MSS)	1
liver metastases	Detailed Description	PD-L1/CD274 PD-1/CD279 Microsatellite Stable (MSS) 1 more biomarker names Show less	1 1 1
liver metastases	Eligibility Criteria	Vascular endothelial growth factor A (VEGF) RAS PMS2 MSH6 MSH2 MLH1 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) KRAS Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Creatinine BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) 14 more biomarker names Show less	1 1 1 1 1 1 2 2 3 1 1 2 1 1 1 1
liver metastases	Official Title	Microsatellite Stable (MSS) cytotoxic T-lymphocyte-associated protein 4	2 2
liver metastases	Brief Summary	Microsatellite Stable (MSS)	3
lung cancer	EligibilityCriteria	Epidermal growth factor receptor (EGFR)	1
lung cancer	Outcome Measure	PD-L1/CD274 Neuron-specific enolase (NSE)	1 1
lung cancer	Detailed Description	PD-L1/CD274	2
lung cancer	Eligibility Criteria	Thyroid stimulating hormone beta (TSH) somatostatin ROS1 RET PSA Nuclear protein Ki67 Anaplastic lymphoma receptor tyrosine kinase (ALP) 5 more biomarker names Show less	1 1 1 1 1 1 1
lung cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	2 1
lymphoma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 Luteinizing hormone (LH) Inhibin A Cytokeratin 20 Creatinine BRAF B-lymphocyte antigen CD20 Alpha-fetoprotein (AFP) Adenosine diphosphate ribose 8 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1
lymphoma	Official Title	PD-L1/CD274 Interleukin-23 (IL-23) interleukin 37 1 more biomarker names Show less	1 1 1
lymphoma	Outcome Measure	PD-L1/CD274	2
male breast cancer	Arm Group Label	Microsatellite Instable (MSI)	1
male breast cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) T-Cell differentiation antigen CD8 PD-L1/CD274 BRCA2 BRCA1 3 more biomarker names Show less	1 1 4 1 1
male breast cancer	OutcomeMeasure	Ataxia telangiectasia mutated	1
male breast cancer	Brief Title	HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4	4 1
male breast cancer	Arm Group Description	Microsatellite Instable (MSI) HER2/ERBB2	1 1
male breast cancer	Detailed Description	PGR HER2/ERBB2 Estrogen receptor alpha (ER alpha) cytotoxic T-lymphocyte-associated protein 4 2 more biomarker names Show less	1 4 1 1
male breast cancer	Eligibility Criteria	Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 RAS RAD54L RAD51 paralog D RAD51 paralog C RAD51 paralog B protein phosphatase 2 regulatory subunit Balpha PGR PD-L1/CD274 partner and localizer of BRCA2 Nuclear protein Ki67 Nibrin neuralized E3 ubiquitin protein ligase 1 MRE11 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) hypertrichosis 2 (generalized, congenital) HER2/ERBB2 FSH Fanconi anemia, complementation group L FANCA Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) Cyclin-dependent kinase 4 (CDK4) cyclin-dependent kinase 12 CHK2 CHK1 Butyl nitrite BRCA2 BRCA1 interacting protein C-terminal helicase 1 BRCA1 associated RING domain 1 BRCA1 Ataxia telangiectasia mutated artemin 34 more biomarker names Show less	1 1 1 1 1 1 1 1 6 1 1 1 1 1 1 1 1 3 1 14 3 1 1 5 1 1 1 1 1 1 1 1 1 1 1 1
male breast cancer	Official Title	PD-L1/CD274 PARP-1 HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 collagen, type XI, alpha 2 3 more biomarker names Show less	2 1 5 1 1
male breast cancer	Brief Summary	Microsatellite Stable (MSS) Microsatellite Instable (MSI) HER2/ERBB2 Estrogen receptor alpha (ER alpha) 2 more biomarker names Show less	1 1 5 1
malignant fibrous histiocytoma	Eligibility Criteria	PD-L1/CD274 MXLPO amelogenin, X-linked 1 more biomarker names Show less	1 1 1
malignant melanoma	Arm Group Label	Microsatellite Instable (MSI)	1
malignant melanoma	Outcome Measure	T-Cell differentiation antigen CD8 RAD50 PD-L1/CD274 PD-1/CD279 Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) gp100 FOXP3 6 more biomarker names Show less	2 1 4 1 1 1 1 1
malignant melanoma	Brief Title	PD-L1/CD274 PD-1/CD279 Human Microbiome 1 more biomarker names Show less	1 1 1
malignant melanoma	Arm Group Description	PD-L1/CD274 PD-1/CD279 Microsatellite Instable (MSI) 1 more biomarker names Show less	1 1 2
malignant melanoma	Detailed Description	tumor necrosis factor receptor superfamily member 9 trophoblast glycoprotein T-Cell differentiation antigen CD8 PD-1/CD279 LAG-3 (CD223) HAVCR2 (TIM-3) BRAF 5 more biomarker names Show less	1 1 1 1 1 1 1
malignant melanoma	Eligibility Criteria	trophoblast glycoprotein Serum albumin PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) MHC class I antigen HLA-A heavy chain (HLA-A) Luteinizing hormone (LH) HLA-A HER2/ERBB2 glycosylated serum albumin FSH Epidermal growth factor receptor (EGFR) Cytokeratin 18 Butanone BRAF Ataxia telangiectasia mutated Anaplastic lymphoma receptor tyrosine kinase (ALP) Alkaline phosphatase (ALPL) 18 more biomarker names Show less	1 1 2 1 1 1 1 1 1 1 2 1 1 1 1 1 3 1 1 1
malignant melanoma	Official Title	PD-L1/CD274 PD-1/CD279 Human Microbiome 1 more biomarker names Show less	2 1 1
malignant melanoma	Brief Summary	PD-1/CD279 BRAF	2 2
Malignant-mesothelioma	Eligibility Criteria	PD-L1/CD274	2
Malignant-mesothelioma	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 Inducible T cell co-stimulator (ICOS) 2 more biomarker names Show less	1 1 3 1
mantle-cell lymphoma	Eligibility Criteria	B-lymphocyte antigen CD19	1
mantle-cell lymphoma	Official Title	PD-L1/CD274	1
mantle-cell lymphoma	Outcome Measure	PD-L1/CD274	1
Merkel cell carcinoma	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI)	1 1
Merkel cell carcinoma	Brief Title	PD-L1/CD274	1
Merkel cell carcinoma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) HER2/ERBB2 Epidermal growth factor receptor (EGFR) Cytokeratin 18 Butanone BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) Alkaline phosphatase (ALPL) 10 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1
Merkel cell carcinoma	Official Title	PD-L1/CD274	2
mesothelioma	Detailed Description	trophoblast glycoprotein	1
mesothelioma	Eligibility Criteria	trophoblast glycoprotein HER2/ERBB2	1 1
mesothelioma	Outcome Measure	PD-L1/CD274 PD-1/CD279	1 1
mouth neoplasm	Brief Summary	p16 H3P10	1 1
mouth neoplasm	Detailed Description	T-Cell differentiation antigen CD8 PD-L1/CD274 p16 H3P10 cytotoxic T-lymphocyte-associated protein 4 3 more biomarker names Show less	1 3 1 1 1
mouth neoplasm	Eligibility Criteria	T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 p16 Luteinizing hormone (LH) H3P10 DPYD cytotoxic T-lymphocyte-associated protein 4 Cystatin C Creatinine 8 more biomarker names Show less	1 3 1 4 4 4 1 1 1 1
mouth neoplasm	Outcome Measure	T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 p16 H3P10 CXCR4 4 more biomarker names Show less	3 3 1 1 1 1
multiple myeloma	Arm Group Description	Creatinine	1
multiple myeloma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 Luteinizing hormone (LH) Hematopoietic progenitor cell antigen CD34 Fc fragment of IgG receptor Ib cytotoxic T-lymphocyte-associated protein 4 CA125 ovarian cancer antigen (MUC16) 5 more biomarker names Show less	1 1 1 1 1 1 1
mycosis fungoides	Detailed Description	T-cell surface antigen CD4	1
mycosis fungoides	Eligibility Criteria	TSPYL2	1
myelodysplastic syndromes	Eligibility Criteria	PML-RARA fusion FANCB C-Kit 1 more biomarker names Show less	1 2 1
myelofibrosis	Detailed Description	T-cell surface antigen CD4 PD-L1/CD274 PD-1/CD279 L-selectin interleukin 7 receptor CD25 (IL2RA) 4 more biomarker names Show less	1 1 1 1 1 1
myelofibrosis	Outcome Measure	PD-L1/CD274 PD-1/CD279	1 1
nasopharyngeal cancer	Arm Group Label	Microsatellite Instable (MSI)	1
nasopharyngeal cancer	Outcome Measure	T-Cell differentiation antigen CD8 PD-L1/CD274 L-Tryptophan Kynurenine Indoleamine 2, 3-dioxygenase 1 (IDO1) D-Tryptophan 4 more biomarker names Show less	1 3 1 1 1 1
nasopharyngeal cancer	Arm Group Description	Microsatellite Instable (MSI)	1
nasopharyngeal cancer	Detailed Description	PD-L1/CD274	1
nasopharyngeal cancer	Eligibility Criteria	T-cell surface antigen CD4 PD-L1/CD274 Luteinizing hormone (LH) LOC102724197 L-Aspartic acid GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase light chain 1 gamma-glutamyltransferase 2 9 more biomarker names Show less	1 1 2 1 1 1 1 1 1 1 1
nasopharyngeal cancer	Brief Summary	PD-L1/CD274	1
Nervous system neoplasms	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
Nervous system neoplasms	Outcome Measure	PD-L1/CD274	1
neuroendocrine carcinoma	Brief Title	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine carcinoma	Detailed Description	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine carcinoma	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 T-cell surface antigen CD4 PD-L1/CD274 Luteinizing hormone (LH) FSH Epidermal growth factor receptor (EGFR) ARID1A 10 more biomarker names Show less	1 1 1 1 1 1 1 1 2 1 1 1
neuroendocrine carcinoma	Official Title	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine carcinoma	Brief Summary	Epidermal growth factor receptor (EGFR)	1
neuroendocrine tumours	Outcome Measure	PD-L1/CD274 Neuron-specific enolase (NSE)	1 1
neuroendocrine tumours	Brief Title	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine tumours	Detailed Description	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine tumours	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 T-cell surface antigen CD4 somatostatin PSA PD-L1/CD274 Nuclear protein Ki67 Luteinizing hormone (LH) FSH Epidermal growth factor receptor (EGFR) ARID1A 13 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 2 1 1 1
neuroendocrine tumours	Official Title	Epidermal growth factor receptor (EGFR) ARID1A	1 1
neuroendocrine tumours	Brief Summary	Epidermal growth factor receptor (EGFR)	1
non-Hodgkin's lymphoma	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 Cytokeratin 20 CA125 ovarian cancer antigen (MUC16) c-Myc BRAF Bcl-6 B-lymphocyte antigen CD20 B-lymphocyte antigen CD19 B-cell lymphoma 2 (Bcl-2) 8 more biomarker names Show less	1 2 1 1 2 1 2 1 1 2
non-Hodgkin's lymphoma	Official Title	Interleukin-23 (IL-23) interleukin 37 B-lymphocyte antigen CD19 1 more biomarker names Show less	1 1 1
non-Hodgkin's lymphoma	Outcome Measure	PD-L1/CD274	1
non-small cell lung cancer	Arm Group Label	PD-L1/CD274 Microsatellite Instable (MSI) cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	1 1 1
non-small cell lung cancer	Outcome Measure	Uric acid tumor-associated calcium signal transducer 2 Tumor Mutational Burden Transforming growth factor-beta (TGF-beta) Thyroid stimulating hormone beta (TSH) T-Cell differentiation antigen CD8 STAT3 PSA PD-L1/CD274 PD-1/CD279 PAI-1 Lactate dehydrogenase (LDH) L-Aspartic acid GINS complex subunit 2 FOXP3 Epidermal growth factor receptor (EGFR) Creatinine c-Met Bruton's tyrosine kinase (BTK) Bilirubin Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Alkaline phosphatase (ALPL) 21 more biomarker names Show less	1 1 3 1 3 2 2 1 29 1 1 1 2 1 1 2 2 1 2 2 1 3 2
non-small cell lung cancer	Brief Title	PD-L1/CD274 PD-1/CD279 KRAS Human Microbiome HER2/ERBB2 Epidermal growth factor receptor (EGFR) 4 more biomarker names Show less	5 1 1 2 1 2
non-small cell lung cancer	Arm Group Description	VEGFR PIK3CA PD-L1/CD274 PD-1/CD279 KRAS Human Microbiome HER2/ERBB2 Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) Cyclin D3 Cyclin D2 Cyclin D1 c-Met 15 more biomarker names Show less	1 1 13 1 1 1 1 1 2 2 2 2 2 1 1 1 1
non-small cell lung cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) Tumor Mutational Burden trophoblast glycoprotein T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PIK3CA Phosphatidylinositols PD-L1/CD274 PD-1/CD279 HER2/ERBB2 GUCY2EP glutaryl-CoA dehydrogenase Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) Fibroblast Growth Factor (FGF2) Epidermal growth factor receptor (EGFR) Cyclin-dependent kinase 4 (CDK4) Cyclin D3 Cyclin D2 Cyclin D1 Cholangitis, primary sclerosing CD3 gamma chain (CD3G) BRCA1 Anaplastic lymphoma receptor tyrosine kinase (ALP) 25 more biomarker names Show less	1 1 1 1 1 2 1 1 1 10 1 1 1 1 1 1 1 1 4 1 1 1 1 1 1 1 2
non-small cell lung cancer	Eligibility Criteria	UV radiation resistance associated tumor-associated calcium signal transducer 2 TTF1 trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 Serum albumin ROS1 retinal pigment epithelium-specific protein 65kDa RET PSA PMS2 PD-L2 PD-L1/CD274 PD-1/CD279 p63 NK2 homeobox 1 neuralized E3 ubiquitin protein ligase 1 MSH6 MSH2 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) MDR1 Luteinizing hormone (LH) KRAS HER2/ERBB2 glycosylated serum albumin FSH Estradiol-17beta 3-sulfate Erythropoietin (EPO) Epidermal growth factor receptor (EGFR) EML4 D-threo-Isocitric acid cytotoxic T-lymphocyte-associated protein 4 cytoskeleton-associated protein 4 Cytokeratin 5 Cytokeratin 20 Cytokeratin 18 cytochrome P450 family 2 subfamily B member 6 CYP3A4 CA125 ovarian cancer antigen (MUC16) c-Met Butanone BRCA2 BRCA1 BRAF B-lymphocyte antigen CD20 Anaplastic lymphoma receptor tyrosine kinase (ALP) amelogenin, X-linked Alpha-fetoprotein (AFP) Alkaline phosphatase (ALPL) Adenosine diphosphate ribose 51 more biomarker names Show less	1 1 3 1 2 6 1 16 1 5 5 1 3 31 8 2 1 1 1 1 1 1 2 1 28 3 6 1 4 1 1 52 4 1 5 1 1 1 1 1 1 1 1 1 1 1 9 1 47 1 1 2 1
non-small cell lung cancer	Official Title	STAT3 PD-L1/CD274 PD-1/CD279 KRAS Interleukin-23 (IL-23) interleukin 37 Human Microbiome HER2/ERBB2 Epidermal growth factor receptor (EGFR) Bruton's tyrosine kinase (BTK) 8 more biomarker names Show less	1 14 1 1 1 1 3 1 4 2
non-small cell lung cancer	Brief Summary	T-Cell differentiation antigen CD8 serine/threonine kinase 11 interacting protein PD-L1/CD274 lipoic acid synthetase lipase, member I KRAS HER2/ERBB2 Epidermal growth factor receptor (EGFR) Cholangitis, primary sclerosing centromere protein J Anaplastic lymphoma receptor tyrosine kinase (ALP) 9 more biomarker names Show less	1 1 6 1 1 1 1 8 1 1 7
non-small celllung cancer	Arm Group Description	Microsatellite Instable (MSI)	2
oesophageal cancer	Arm Group Label	PD-L1/CD274 Microsatellite Instable (MSI) cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	1 1 1
oesophageal cancer	Outcome Measure	tumor necrosis factor receptor superfamily, member 4 T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 SMAD4 PD-L1/CD274 PD-1/CD279 Nuclear protein Ki67 Interferon Gamma (IFNg) HER2/ERBB2 GZMB FOXP3 cytotoxic T-lymphocyte-associated protein 4 CD3 gamma chain (CD3G) Caspase-3 (CASP3) 15 more biomarker names Show less	1 1 1 1 1 1 1 5 1 1 1 1 1 2 1 1 1
oesophageal cancer	Brief Title	PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 2 more biomarker names Show less	1 1 1 1
oesophageal cancer	Arm Group Description	VEGFR1 VEGFR RET PDGFRB PDGFRA PD-L1/CD274 Microsatellite Instable (MSI) Interferon Gamma (IFNg) Folinic acid Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) CDK6 CD80 molecule CD177 molecule 13 more biomarker names Show less	1 1 1 1 1 4 2 1 1 1 2 1 1 1 1
oesophageal cancer	Detailed Description	teneurin transmembrane protein 1 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 p16 Microsatellite Instable (MSI) HER2/ERBB2 H3P10 Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 11 more biomarker names Show less	1 1 4 1 1 1 2 1 1 1 1 1 1
oesophageal cancer	Eligibility Criteria	Uridine 5'-diphosphate UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor necrosis factor alpha (TNF-alpha) Tumor Mutational Burden TGFBR1 Serum albumin PSA PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 PD-1/CD279 p16 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Stable (MSS) Microsatellite Instable (MSI) mannose receptor, C type 1 Luteinizing hormone (LH) Insulin HER2/ERBB2 H3P10 glycosylated serum albumin FSH Fibroblast growth factor receptor 1 (FGFR1) Epidermal growth factor receptor (EGFR) DPYD Cytokeratin 18 Cyclin-dependent kinase 4 (CDK4) Butanone BRAF Ataxia telangiectasia mutated Anaplastic lymphoma receptor tyrosine kinase (ALP) Alpha-fetoprotein (AFP) 38 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 4 3 1 1 1 1 4 1 2 1 4 1 1 1 1 3 2 1 1 1 1 1 1 1
oesophageal cancer	Official Title	PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 2 more biomarker names Show less	3 1 1 2
oesophageal cancer	Brief Summary	PD-L1/CD274 mannose receptor, C type 1 HER2/ERBB2 1 more biomarker names Show less	1 1 2
oligodendroglioma	Brief Summary	Isocitric acid IDH2 IDH1 1 more biomarker names Show less	1 1 1
oligodendroglioma	Detailed Description	IDH2 IDH1	1 1
oligodendroglioma	Eligibility Criteria	IDH2 IDH1	1 1
oropharyngeal cancer	Outcome Measure	T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PD-L1/CD274 p16 mannosidase alpha class 2C member 1 HPV E6 H3P10 FOXP3 Cytokeratin 20 CD38 CD3 gamma chain (CD3G) B-lymphocyte antigen CD20 12 more biomarker names Show less	1 1 1 3 4 2 1 1 2 1 1 1 1 1
oropharyngeal cancer	Brief Title	iroquois homeobox 2	1
oropharyngeal cancer	Arm Group Description	iroquois homeobox 2	1
oropharyngeal cancer	Detailed Description	T-Cell differentiation antigen CD8 PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 p16 KRAS HPV E6 H3P10 cytotoxic T-lymphocyte-associated protein 4 9 more biomarker names Show less	2 1 1 1 1 3 2 1 1 2 1
oropharyngeal cancer	Eligibility Criteria	T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 p16 Luteinizing hormone (LH) H3P10 DPYD cytotoxic T-lymphocyte-associated protein 4 Cystatin C Creatinine 8 more biomarker names Show less	1 5 1 9 7 9 1 1 1 1
oropharyngeal cancer	Official Title	iroquois homeobox 2	1
osteosarcoma	Detailed Description	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 1 1 1
osteosarcoma	Eligibility Criteria	PD-L1/CD274 Luteinizing hormone (LH) Inhibin A Creatinine Alpha-fetoprotein (AFP) 3 more biomarker names Show less	1 1 1 1 1
osteosarcoma	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 5'-nucleotidase ecto 3 more biomarker names Show less	1 1 2 1 1
ovarian cancer	Arm Group Label	Microsatellite Instable (MSI)	1
ovarian cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) tubulin folding cofactor E T-Cell differentiation antigen CD8 PSA PD-L1/CD274 GINS complex subunit 2 CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 Ataxia telangiectasia mutated 8 more biomarker names Show less	1 1 1 2 5 1 2 1 1 1
ovarian cancer	Brief Title	PD-L1/CD274 BRCA2 BRCA1 1 more biomarker names Show less	2 1 1
ovarian cancer	Arm Group Description	Microsatellite Instable (MSI) Granulocyte-macrophage colony-stimulating factor (GM-CSF) ARID1A 1 more biomarker names Show less	1 1 1
ovarian cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) tubulin folding cofactor E trophoblast glycoprotein T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PD-1/CD279 Pancreatic lipase mannose receptor, C type 1 HER2/ERBB2 FOXP3 cytotoxic T-lymphocyte-associated protein 4 CD3 gamma chain (CD3G) BRCA2 BRCA1 16 more biomarker names Show less	1 3 1 1 1 1 1 1 3 1 1 1 1 1 1 1 1 2
ovarian cancer	Eligibility Criteria	WT1 UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 tubulin folding cofactor E trophoblast glycoprotein Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 ROS1 RAS PSA protein phosphatase 2, regulatory subunit A, alpha phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PD-L1/CD274 PD-1/CD279 PARP-1 Microsatellite Stable (MSS) Luteinizing hormone (LH) HER2/ERBB2 FSH Estrogen receptor alpha (ER alpha) Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 CYP3A4 Cyclin-dependent kinase 4 (CDK4) Creatine collagen, type XI, alpha 2 CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 BRAF Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Alkaline phosphatase (ALPL) Adenosine diphosphate ribose 40 more biomarker names Show less	1 1 1 1 1 1 1 1 1 2 3 1 1 1 1 1 1 5 1 1 1 11 5 5 1 1 3 2 1 1 1 1 4 5 3 2 1 1 2 2 1 1
ovarian cancer	Official Title	PD-L1/CD274 PARP-1 HER2/ERBB2 cytotoxic T-lymphocyte-associated protein 4 collagen, type XI, alpha 2 BRCA2 BRCA1 5 more biomarker names Show less	4 1 1 1 1 1 1
ovarian cancer	Brief Summary	Microsatellite Stable (MSS) HER2/ERBB2 Estrogen receptor alpha (ER alpha) BRCA2 BRCA1 3 more biomarker names Show less	1 1 1 1 1
pancreatic cancer	Arm Group Label	Microsatellite Instable (MSI)	1
pancreatic cancer	Outcome Measure	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 STAT3 SMAD4 PSA PD-L1/CD274 Neuron-specific enolase (NSE) Carbohydrate antigen 19-9 (CA 19-9) Bruton's tyrosine kinase (BTK) 7 more biomarker names Show less	1 3 2 1 1 3 1 2 2
pancreatic cancer	Brief Title	PD-L1/CD274 KRAS Colony stimulating factor 1 receptor (CSF1R) 1 more biomarker names Show less	2 1 1
pancreatic cancer	Arm Group Description	Microsatellite Instable (MSI) Macrophage colony stimulating factor (MCSF) Interferon Gamma (IFNg) HER2/ERBB2 Folinic acid ARID1A 4 more biomarker names Show less	1 1 1 1 1 1
pancreatic cancer	Detailed Description	tubulin folding cofactor E trophoblast glycoprotein STAT3 PD-L1/CD274 PD-1/CD279 p63 KRAS Interferon Gamma (IFNg) cytotoxic T-lymphocyte-associated protein 4 Carbohydrate antigen 19-9 (CA 19-9) Adenosine diphosphate ribose 9 more biomarker names Show less	1 1 1 5 2 1 1 1 1 1 1
pancreatic cancer	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 tubulin folding cofactor E trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 somatostatin PSA PD-L1/CD274 PD-1/CD279 p63 Nuclear protein Ki67 Luteinizing hormone (LH) KRAS Interferon Gamma (IFNg) HER2/ERBB2 FSH Epidermal growth factor receptor (EGFR) DPYD discoidin domain receptor tyrosine kinase 1 cytotoxic T-lymphocyte-associated protein 4 CA125 ovarian cancer antigen (MUC16) BRCA2 Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) 29 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 4 1 2 1 1 4 1 1 2 2 2 1 1 2 1 1 1 1 1
pancreatic cancer	Official Title	Transforming growth factor-beta (TGF-beta) STAT3 PD-L1/CD274 KRAS cytotoxic T-lymphocyte-associated protein 4 Colony stimulating factor 1 receptor (CSF1R) Bruton's tyrosine kinase (BTK) 5'-nucleotidase ecto 6 more biomarker names Show less	1 1 3 1 1 1 2 1
pancreatic cancer	Brief Summary	KRAS	1
pelvic cancer	Arm Group Description	Creatinine	1
pelvic cancer	Eligibility Criteria	PSA Luteinizing hormone (LH)	1 1
pelvic cancer	Official Title	Transforming growth factor-beta (TGF-beta)	1
pelvic cancer	Outcome Measure	Transthyretin Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) 1 more biomarker names Show less	1 1 1
penile cancer	Arm Group Description	Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35)	1 1
penile cancer	Detailed Description	PD-L1/CD274	1
penile cancer	Eligibility Criteria	T-cell surface antigen CD4	1
periampullary cancer	Detailed Description	PD-L1/CD274 betacellulin	1 1
periampullary cancer	Eligibility Criteria	Luteinizing hormone (LH) FSH	1 1
peripheral T-cell lymphoma	Arm Group Description	Folic acid Cyanocobalamin Cobalamin 1 more biomarker names Show less	1 1 1
peripheral T-cell lymphoma	Detailed Description	T-cell surface antigen CD4	1
peripheral T-cell lymphoma	Eligibility Criteria	TSPYL2 cytotoxic T-lymphocyte-associated protein 4	1 1
peritoneal cancer	Outcome Measure	tubulin folding cofactor E PSA PD-L1/CD274 GINS complex subunit 2 CA125 ovarian cancer antigen (MUC16) 3 more biomarker names Show less	1 1 3 1 2
peritoneal cancer	Brief Title	PD-L1/CD274 BRCA2 BRCA1 1 more biomarker names Show less	2 1 1
peritoneal cancer	Arm Group Description	Granulocyte-macrophage colony-stimulating factor (GM-CSF)	1
peritoneal cancer	Detailed Description	tubulin folding cofactor E T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PD-1/CD279 Pancreatic lipase mannose receptor, C type 1 FOXP3 CD3 gamma chain (CD3G) BRCA2 BRCA1 12 more biomarker names Show less	2 1 1 1 1 1 3 1 1 1 1 1 1 1
peritoneal cancer	Eligibility Criteria	Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 protein phosphatase 2, regulatory subunit A, alpha PD-L1/CD274 PARP-1 Luteinizing hormone (LH) HER2/ERBB2 FSH Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 CYP3A4 collagen, type XI, alpha 2 CA125 ovarian cancer antigen (MUC16) BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Adenosine diphosphate ribose 19 more biomarker names Show less	1 2 1 1 3 1 8 1 3 1 1 1 1 1 3 4 3 1 1 2 1
peritoneal cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4 BRCA2 BRCA1 2 more biomarker names Show less	2 1 1 1
peritoneal cancer	Brief Summary	BRCA2 BRCA1	1 1
plasmacytoma	Brief Title	PD-L1/CD274	1
plasmacytoma	Eligibility Criteria	Luteinizing hormone (LH)	1
prostate cancer	Arm Group Label	WEE1 PLK4 PD-L1/CD274 Androgen Receptor (AR) 2 more biomarker names Show less	1 1 1 1
prostate cancer	Outcome Measure	Testosterone T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PSA PD-L1/CD274 CD3 gamma chain (CD3G) 6 more biomarker names Show less	1 2 2 1 1 9 3 2
prostate cancer	Brief Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	2 2
prostate cancer	Arm Group Description	Microsatellite Instable (MSI) cyclin-dependent kinase 12 ARID1A 1 more biomarker names Show less	1 1 1
prostate cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) tubulin folding cofactor E trophoblast glycoprotein T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PSA PD-L1/CD274 Microsatellite Instable (MSI) Inducible T cell co-stimulator (ICOS) cyclin-dependent kinase 12 CD3 gamma chain (CD3G) BRCA1 11 more biomarker names Show less	1 1 1 2 2 1 2 1 2 1 1 2 1
prostate cancer	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor Mutational Burden tubulin folding cofactor E trophoblast glycoprotein Testosterone T-cell surface antigen CD4 solute carrier organic anion transporter family member 1B3 solute carrier family 22 member 6 SLCO1B1 ROS1 RAD51 paralog D RAD51 paralog C PSA POU class 2 homeobox 2 potassium channel, two pore domain subfamily K, member 3 partner and localizer of BRCA2 OCT2 OCT1 Nibrin MRE11 Microsatellite Instable (MSI) MDR1 MATE1 Luteinizing hormone (LH) HER2/ERBB2 gonadotropin releasing hormone 1 Gonadotropin releasing hormone GEN1, Holliday junction 5' flap endonuclease FSH family with sequence similarity 175, member A Epidermal growth factor receptor (EGFR) DNA (cytosine-5-)-methyltransferase 3 beta cyclin-dependent kinase 12 CHK2 chaperonin containing TCP1 subunit 3 CA125 ovarian cancer antigen (MUC16) Butyl nitrite BRCA2 BRCA1 BRAF ATP binding cassette subfamily G member 2 (Junior blood group) Ataxia telangiectasia mutated artemin ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) 48 more biomarker names Show less	1 1 1 1 1 1 1 1 1 6 2 1 1 1 1 1 1 9 1 1 1 1 1 1 1 3 1 1 1 2 2 1 1 1 1 2 1 1 1 1 1 1 3 2 2 1 2 1 1 2
prostate cancer	Official Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	2 2
prostate cancer	Brief Summary	PSA	1
pulmonary blastoma	Brief Summary	Cholangitis, primary sclerosing	1
pulmonary blastoma	Detailed Description	Cholangitis, primary sclerosing	1
pulmonary blastoma	Eligibility Criteria	Luteinizing hormone (LH)	1
pulmonary blastoma	Outcome Measure	PD-L1/CD274 c-Met	1 1
rectal cancer	Outcome Measure	T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) cleavage and polyadenylation specific factor 4 CD3 gamma chain (CD3G) 2 more biomarker names Show less	1 1 1 1
rectal cancer	Brief Title	Microsatellite Stable (MSS) Microsatellite Instable (MSI)	1 1
rectal cancer	Detailed Description	Microsatellite Stable (MSS)	1
rectal cancer	Eligibility Criteria	receptor accessory protein 5 PMS2 MSH6 MSH2 MLH1 Microsatellite Stable (MSS) Luteinizing hormone (LH) DPYD 6 more biomarker names Show less	1 1 1 1 1 1 2 1
rectal cancer	Official Title	PD-L1/CD274 Microsatellite Stable (MSS) cytotoxic T-lymphocyte-associated protein 4 1 more biomarker names Show less	1 1 1
rectal cancer	Brief Summary	Microsatellite Instable (MSI) mannose receptor, C type 1	1 1
renal cancer	Outcome Measure	Thyroxine (T4) PD-L1/CD274 Hydrocortisone GTP binding protein 1 glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 enhancer of mRNA decapping 4 Creatinine Creatine CD36 molecule (thrombospondin receptor) Cardiac Troponin I C-reactive protein (CRP) BNP Bilirubin 19 more biomarker names Show less	1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
renal cancer	Brief Title	Human Microbiome	1
renal cancer	Arm Group Description	Creatinine	1
renal cancer	Detailed Description	Inducible T cell co-stimulator (ICOS)	1
renal cancer	Eligibility Criteria	PSA PD-L1/CD274 Luteinizing hormone (LH) CA125 ovarian cancer antigen (MUC16) 2 more biomarker names Show less	2 1 2 1
renal cancer	Official Title	Human Microbiome cytotoxic T-lymphocyte-associated protein 4	1 1
renal cell carcinoma	Arm Group Label	Microsatellite Instable (MSI)	1
renal cell carcinoma	Outcome Measure	T-Cell differentiation antigen CD8 PSA PD-L1/CD274 Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) FOXP3 c-Met 5 more biomarker names Show less	3 1 3 1 1 1 1
renal cell carcinoma	Brief Title	PD-L1/CD274 papillary renal cell carcinoma (translocation-associated) Human Microbiome 1 more biomarker names Show less	1 1 1
renal cell carcinoma	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) ARID1A 1 more biomarker names Show less	1 2 1
renal cell carcinoma	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) trophoblast glycoprotein T-Cell differentiation antigen CD8 papillary renal cell carcinoma (translocation-associated) cytotoxic T-lymphocyte-associated protein 4 BRCA1 4 more biomarker names Show less	1 1 2 1 1 1
renal cell carcinoma	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 trophoblast glycoprotein Serum albumin ROS1 PSA PD-L1/CD274 PD-1/CD279 papillary renal cell carcinoma (translocation-associated) neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) Luteinizing hormone (LH) HER2/ERBB2 glycosylated serum albumin FSH Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 18 Butanone BRAF Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) Alkaline phosphatase (ALPL) 27 more biomarker names Show less	1 1 1 1 1 1 1 1 2 3 3 2 1 1 1 1 4 2 1 2 4 1 1 1 3 1 1 4 1
renal cell carcinoma	Official Title	PD-L1/CD274 Human Microbiome	2 1
renal cell carcinoma	Brief Summary	T-Cell differentiation antigen CD8 PD-L1/CD274 papillary renal cell carcinoma (translocation-associated) cytotoxic T-lymphocyte-associated protein 4 c-Met 3 more biomarker names Show less	1 1 1 1 1
renal cellcarcinoma	Detailed Description	PD-L1/CD274	1
rhabdomyosarcoma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
rhabdomyosarcoma	Outcome Measure	PD-L1/CD274	1
salivary gland cancer	Eligibility Criteria	PD-L1/CD274 CA125 ovarian cancer antigen (MUC16)	1 1
salivary gland cancer	Outcome Measure	PD-1/CD279	1
sarcoma	Outcome Measure	tubulin folding cofactor E T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 GINS complex subunit 2 c-Met 5'-nucleotidase ecto 6 more biomarker names Show less	1 1 1 2 1 1 1 1
sarcoma	Brief Title	ARID1A	1
sarcoma	Detailed Description	T-cell surface antigen CD4 T-Cell differentiation antigen CD8 PD-L1/CD274 PD-1/CD279 Cholangitis, primary sclerosing ARID1A 5'-nucleotidase ecto 5 more biomarker names Show less	1 1 1 1 1 1 1
sarcoma	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 PD-L1/CD274 PARP-1 Microsatellite Instable (MSI) Luteinizing hormone (LH) collagen, type XI, alpha 2 CA125 ovarian cancer antigen (MUC16) BRCA2 ARID1A ALT 13 more biomarker names Show less	1 1 1 1 1 1 1 1 1 4 1 1 1 1 1
sarcoma	Official Title	ARID1A	1
sarcoma	Brief Summary	Cholangitis, primary sclerosing	1
seminoma	Eligibility Criteria	PSA Luteinizing hormone (LH) hypertrichosis 2 (generalized, congenital) chorionic gonadotropin beta subunit 5 CGA Alpha-fetoprotein (AFP) 4 more biomarker names Show less	1 1 1 1 1 1
Sezary syndrome	Detailed Description	T-cell surface antigen CD4	1
Sezary syndrome	Eligibility Criteria	TSPYL2	1
skin cancer	Arm Group Label	PD-L1/CD274	1
skin cancer	Outcome Measure	PD-L1/CD274 gp100	1 1
skin cancer	Brief Title	PD-L1/CD274	1
skin cancer	Detailed Description	RAC-alpha serine/threonine-protein kinase (AKT) PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 PD-1/CD279 mTOR Insulin IGF1 8 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1
skin cancer	Eligibility Criteria	PD-L1/CD274 PD-1/CD279 MHC class I antigen HLA-A heavy chain (HLA-A) HLA-A Cytokeratin 20 BRAF B-lymphocyte antigen CD20 5 more biomarker names Show less	1 1 1 1 1 2 1
skin cancer	Official Title	PD-L1/CD274 Interleukin-23 (IL-23) interleukin 37 1 more biomarker names Show less	1 1 1
skin cancer	Brief Summary	PD-1/CD279 BRAF	1 1
small cell lung cancer	Arm Group Label	Microsatellite Instable (MSI)	1
small cell lung cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) Thyroid stimulating hormone beta (TSH) T-Cell differentiation antigen CD8 PSA PD-L1/CD274 L-Aspartic acid Inducible T cell co-stimulator (ICOS) FOXP3 Creatinine c-Myc BRCA2 BRCA1 Bilirubin Ataxia telangiectasia mutated ALT 13 more biomarker names Show less	1 1 2 1 4 1 1 1 1 1 1 1 1 1 1
small cell lung cancer	Brief Title	PD-L1/CD274 Epidermal growth factor receptor (EGFR)	2 1
small cell lung cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI)	1 2
small cell lung cancer	Detailed Description	Tumor Mutational Burden TERT T-Cell differentiation antigen CD8 schlafen family member 11 pregnancy specific beta-1-glycoprotein 2 PD-L1/CD274 PD-1/CD279 Neuron-specific enolase (NSE) HER2/ERBB2 Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Chemokine IFN-Î³-inducible protein 10 (IP-10/CXCL10) CEA carcinoembryonic antigen related cell adhesion molecule 3 C-C motif chemokine 5 (CCL5 13 more biomarker names Show less	1 1 1 1 1 2 1 1 1 1 1 1 1 1 1
small cell lung cancer	Eligibility Criteria	T-cell surface antigen CD4 Serum albumin PD-L2 PD-L1/CD274 PD-1/CD279 neuralized E3 ubiquitin protein ligase 1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) Luteinizing hormone (LH) HER2/ERBB2 glycosylated serum albumin FSH Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 18 c-Myc Butanone BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT Alkaline phosphatase (ALPL) 21 more biomarker names Show less	3 1 1 2 3 1 1 1 11 3 1 4 3 3 1 1 1 1 1 2 2 1 1
small cell lung cancer	Official Title	PD-L1/CD274 PARP-1 Epidermal growth factor receptor (EGFR) collagen, type XI, alpha 2 2 more biomarker names Show less	3 1 1 2
small cell lung cancer	Brief Summary	Epidermal growth factor receptor (EGFR)	1
soft tissue sarcoma	Arm Group Label	Microsatellite Instable (MSI)	1
soft tissue sarcoma	Outcome Measure	PD-L1/CD274	1
soft tissue sarcoma	Arm Group Description	Microsatellite Instable (MSI) Interferon Gamma (IFNg)	1 1
soft tissue sarcoma	Detailed Description	Interferon Gamma (IFNg)	1
soft tissue sarcoma	Eligibility Criteria	Thyroxine (T4) Thyroid stimulating hormone beta (TSH) phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha MXLPO Interferon Gamma (IFNg) Epidermal growth factor receptor (EGFR) Creatine Anaplastic lymphoma receptor tyrosine kinase (ALP) amelogenin, X-linked Alkaline phosphatase (ALPL) 8 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1
soft tissue sarcoma	Official Title	cytotoxic T-lymphocyte-associated protein 4	1
solid tumours	Arm Group Label	Tumor Mutational Burden ROS1 PD-L1/CD274 p16 Microsatellite Instable (MSI) HER2/ERBB2 Epidermal growth factor receptor (EGFR) c-Met C-Kit BRAF 8 more biomarker names Show less	1 1 2 1 1 1 1 1 1 1
solid tumours	Outcome Measure	Vascular endothelial growth factor A (VEGF) ubiquitin associated and SH3 domain containing B Tumor necrosis factor alpha (TNF-alpha) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 STAT3 SMAD4 RPS6 PSA PIK3CA PD-L2 PD-L1/CD274 PD-1/CD279 macrophage scavenger receptor 1 Macrophage colony stimulating factor (MCSF) Interleukin-8 (IL-8) Interleukin-6 (IL-6) Interleukin-5 (IL-5) Interleukin-4 (IL-4) Interleukin-2 (IL-2) Interleukin-13 (IL-13) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) Interleukin-10 (IL-10) interleukin 34 Interleukin 1 Beta (IL-1Î²) Interferon Gamma (IFNg) Granulocyte-macrophage colony-stimulating factor (GM-CSF) FOXP3 Fc gamma RIIIa Fc fragment of IgG, low affinity IIIb, receptor (CD16b) Epidermal growth factor receptor (EGFR) Colony stimulating factor 1 receptor (CSF1R) CD163 Carbohydrate antigen 19-9 (CA 19-9) Bruton's tyrosine kinase (BTK) BRCA2 BRCA1 Ataxia telangiectasia mutated annexin A6 4E-BP1 39 more biomarker names Show less	1 1 1 1 6 3 1 1 2 1 1 12 2 1 1 1 1 1 1 1 1 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
solid tumours	Brief Title	PD-L1/CD274 cytotoxic T-lymphocyte-associated protein 4	4 1
solid tumours	Arm Group Description	Tumor Mutational Burden PD-L1/CD274 PD-1/CD279 Microsatellite Instable (MSI) Interferon Gamma (IFNg) cytotoxic T-lymphocyte-associated protein 4 ARID1A 5 more biomarker names Show less	1 3 1 2 1 1 1
solid tumours	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) Tumor Mutational Burden tubulin folding cofactor E trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) ROS1 RAC-alpha serine/threonine-protein kinase (AKT) Pro-opiomelanocortin (POMC PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 PD-1/CD279 p63 p16 mTOR Interferon Gamma (IFNg) Insulin IGF1 IDH2 IDH1 HER2/ERBB2 Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cardiac Troponin I c-Met C-Kit BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) Adenosine diphosphate ribose 31 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 2 1 2 1 1 1 1 1 1 1 1
solid tumours	Eligibility Criteria	XRCC2 UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor Mutational Burden tubulin folding cofactor E trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 Serum albumin ROS1 RAS RAD54L RAD51 paralog D RAD51 paralog C RAD51 paralog B PTEN PSA Pro-opiomelanocortin (POMC polymerase (DNA directed), delta 1, catalytic subunit PMS2 PIK3CA PD-L1/CD274 PD-1/CD279 partner and localizer of BRCA2 PARP-1 p63 p16 neuralized E3 ubiquitin protein ligase 1 MSH6 MSH2 MRE11 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Stable (MSS) Microsatellite Instable (MSI) Luteinizing hormone (LH) L-Aspartic acid Interferon Gamma (IFNg) Inhibin A IDH2 IDH1 HER2/ERBB2 glycosylated serum albumin FSH Fanconi anemia, complementation group L FANCA Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) discoidin domain receptor tyrosine kinase 1 cytotoxic T-lymphocyte-associated protein 4 Cytokeratin 20 Cytokeratin 18 cyclin-dependent kinase 12 Creatinine Creatine CHK2 CHK1 CA125 ovarian cancer antigen (MUC16) c-Met C-Kit Butanone BRCA2 BRCA1 interacting protein C-terminal helicase 1 BRCA1 associated RING domain 1 BRCA1 BRAF B-lymphocyte antigen CD20 ATRX Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) Alpha-fetoprotein (AFP) Alkaline phosphatase (ALPL) Adenosine diphosphate ribose 77 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 2 3 1 1 3 1 1 1 1 1 1 2 1 1 1 1 6 6 1 1 1 1 1 1 2 1 1 1 1 3 7 1 1 1 1 1 6 1 2 1 1 1 9 2 3 1 1 1 2 1 1 1 1 1 1 1 4 1 1 2 6 1 1 2 2 6 1 1 1
solid tumours	Official Title	PD-L1/CD274 PARP-1 Interleukin-23 (IL-23) interleukin 37 Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 CXCR4 collagen, type XI, alpha 2 Bruton's tyrosine kinase (BTK) 7 more biomarker names Show less	8 1 1 1 1 2 1 1 1
solid tumours	Brief Summary	Tumor Mutational Burden PTEN PIK3CA Microsatellite Stable (MSS) Isocitric acid IDH2 IDH1 HER2/ERBB2 Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) 8 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1
squamous cell cancer	Arm Group Label	PD-L1/CD274 Microsatellite Instable (MSI)	2 1
squamous cell cancer	Outcome Measure	tumor necrosis factor receptor superfamily, member 4 Tumor Mutational Burden Thyroxine (T4) Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 STAT3 PD-L1/CD274 PD-1/CD279 p16 Nuclear protein Ki67 mannosidase alpha class 2C member 1 L-Aspartic acid Interleukin-6 (IL-6) Interleukin-10 (IL-10) Hydrocortisone HPV E6 H3P10 GZMB GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 FOXP3 Cytokeratin 20 CXCR4 Creatinine Creatine CD38 CD3 gamma chain (CD3G) Caspase-3 (CASP3) Cardiac Troponin I C-reactive protein (CRP) Bruton's tyrosine kinase (BTK) BNP Bilirubin B-lymphocyte antigen CD20 ALT 39 more biomarker names Show less	1 1 1 1 3 3 3 7 1 24 3 2 1 1 1 1 1 1 1 2 1 1 1 1 1 1 3 1 1 2 1 1 3 1 1 1 2 1 2 1 1
squamous cell cancer	OutcomeMeasure	cytotoxic T-lymphocyte-associated protein 4	1
squamous cell cancer	Brief Title	PD-L1/CD274 PD-1/CD279 Neprilysin iroquois homeobox 2 cytotoxic T-lymphocyte-associated protein 4 ARID1A 4 more biomarker names Show less	3 1 1 1 2 1
squamous cell cancer	Arm Group Description	VEGFR1 VEGFR RET PIK3CA PDGFRB PDGFRA PD-L1/CD274 Microsatellite Instable (MSI) iroquois homeobox 2 Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) HER2/ERBB2 Fibroblast growth factor receptor 4 (FGFR4) Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) Cyclin D3 Cyclin D2 Cyclin D1 CDK6 CD80 molecule CD177 molecule c-Met 23 more biomarker names Show less	1 2 1 1 1 1 5 2 1 1 1 1 1 2 2 3 1 3 1 1 1 1 1 1 1
squamous cell cancer	Detailed Description	Tumor Mutational Burden trophoblast glycoprotein T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 PIK3CD PIK3CA Phosphatidylinositols phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L1/CD274 PD-1/CD279 p16 KRAS Inducible T cell co-stimulator (ICOS) HPV E6 H3P10 GUCY2EP glutaryl-CoA dehydrogenase Fibroblast growth factor receptor 3 (FGFR3) Fibroblast growth factor receptor 2 (FGFR2) Fibroblast growth factor receptor 1 (FGFR1) Fibroblast Growth Factor (FGF2) Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 Cyclin-dependent kinase 4 (CDK4) Cyclin D3 Cyclin D2 Cyclin D1 CD3 gamma chain (CD3G) ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) 30 more biomarker names Show less	1 1 1 1 4 1 2 1 1 1 16 2 3 1 1 1 3 1 1 1 1 1 1 2 1 1 1 1 1 1 1 2
squamous cell cancer	Eligibility Criteria	UV radiation resistance associated UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 Tumor Mutational Burden TTF1 trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 sideroflexin 1 Serum albumin ROS1 retinal pigment epithelium-specific protein 65kDa RET PSA PMS2 PIK3CD PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PD-L2 PD-L1/CD274 PD-1/CD279 p63 p16 NK2 homeobox 1 neuralized E3 ubiquitin protein ligase 1 MSH6 MSH2 MLH1 mitogen-activated protein kinase kinase 7 Microsatellite Instable (MSI) MDR1 Luteinizing hormone (LH) Insulin HER2/ERBB2 H3P10 glycosylated serum albumin FSH Fibroblast growth factor receptor 1 (FGFR1) Ethenyl acetate Estradiol-17beta 3-sulfate Epidermal growth factor receptor (EGFR) EML4 DPYD D-threo-Isocitric acid cytotoxic T-lymphocyte-associated protein 4 cytoskeleton-associated protein 4 Cytokeratin 5 Cytokeratin 20 Cytokeratin 18 cytochrome P450 family 2 subfamily B member 6 Cystatin C CYP3A4 Cyclin-dependent kinase 4 (CDK4) Creatinine CA125 ovarian cancer antigen (MUC16) c-Met Butanone BRAF B-lymphocyte antigen CD20 ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) amelogenin, X-linked Alpha-fetoprotein (AFP) Adenosine diphosphate ribose 68 more biomarker names Show less	1 1 1 1 1 1 1 1 3 1 3 4 1 1 1 5 1 1 8 1 1 1 1 1 1 25 7 2 14 1 1 1 1 1 1 3 1 26 1 5 14 1 4 1 1 1 17 1 2 1 3 1 1 1 1 1 1 1 1 1 1 1 1 4 1 1 16 1 1 1
squamous cell cancer	Official Title	PD-L1/CD274 PD-1/CD279 iroquois homeobox 2 Interleukin-23 (IL-23) interleukin 37 cytotoxic T-lymphocyte-associated protein 4 Bruton's tyrosine kinase (BTK) ARID1A 6 more biomarker names Show less	9 1 1 1 1 4 2 1
squamous cell cancer	Brief Summary	PD-L1/CD274 p16 H3P10 Epidermal growth factor receptor (EGFR) Anaplastic lymphoma receptor tyrosine kinase (ALP) 3 more biomarker names Show less	2 1 1 2 2
synovial sarcoma	Eligibility Criteria	Inhibin A Creatinine Alpha-fetoprotein (AFP) 1 more biomarker names Show less	1 1 1
synovial sarcoma	Outcome Measure	PD-L1/CD274	1
thyroid cancer	Eligibility Criteria	SHC adaptor protein 3 ribonuclease/angiogenin inhibitor 1 PPP1R13L Luteinizing hormone (LH) growth differentiation factor 1 dicer 1, ribonuclease type III 4 more biomarker names Show less	1 1 1 1 1 1
thyroid cancer	Official Title	dicer 1, ribonuclease type III	1
thyroid cancer	Outcome Measure	PD-1/CD279	1
triple negative breast cancer	Arm Group Label	Microsatellite Instable (MSI)	1
triple negative breast cancer	Outcome Measure	Vascular endothelial growth factor A (VEGF) UBE2C tumor protein p53 binding protein 1 transmembrane p24 trafficking protein 7 Thymidylate synthetase TCEAL1 T-Cell differentiation antigen CD8 Survivin Sjogren syndrome/scleroderma autoantigen 1 SERPINA2 RRM2 replication protein A2 Ras protein specific guanine nucleotide releasing factor 1 RAD51 PTTG1 PSA proteasome 26S subunit, non-ATPase 9 PD-L1/CD274 PD-1/CD279 PCNA PARP-1 p53 (tumor protein p53) NUF2 Nuclear protein Ki67 NKG2D (KLRK1) NDC80 mitogen-activated protein kinase 14 methylmalonic aciduria (cobalamin deficiency) cblB type MAPK1 Mab-21 domain containing 1 LAG-3 (CD223) Interferon Gamma (IFNg) HER2/ERBB2 H3P23 FOXP3 Estrogen receptor alpha (ER alpha) dynactin subunit 6 DNA polymerase delta interacting protein 2 discoidin domain receptor tyrosine kinase 1 Cyclin B1 CXCL9 CRK proto-oncogene, adaptor protein collagen, type XI, alpha 2 CEP55 cell division cycle 25C CDKN1B CDC20 BRCA2 BRCA1 ATR Ataxia telangiectasia mutated anthrax toxin receptor 1 activator of HSP90 ATPase activity 1 5'-nucleotidase ecto 52 more biomarker names Show less	1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 8 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1
triple negative breast cancer	Brief Title	PD-L1/CD274 HER2/ERBB2 Estrogen receptor alpha (ER alpha) 1 more biomarker names Show less	2 2 1
triple negative breast cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) HER2/ERBB2 1 more biomarker names Show less	1 1 1
triple negative breast cancer	Detailed Description	trophoblast glycoprotein PGR PD-L1/CD274 Estrogen receptor alpha (ER alpha) cytotoxic T-lymphocyte-associated protein 4 3 more biomarker names Show less	1 2 1 1 1
triple negative breast cancer	Eligibility Criteria	trophoblast glycoprotein Thyroid stimulating hormone beta (TSH) T-cell surface antigen CD4 Serum albumin PGR PD-L1/CD274 Nuclear protein Ki67 neuralized E3 ubiquitin protein ligase 1 Luteinizing hormone (LH) HER2/ERBB2 glycosylated serum albumin FSH Estrogen receptor alpha (ER alpha) Epidermal growth factor receptor (EGFR) CYP3A4 chaperonin containing TCP1 subunit 3 BRCA2 BRCA1 BRAF Anaplastic lymphoma receptor tyrosine kinase (ALP) ALT 5'-nucleotidase ecto 20 more biomarker names Show less	1 1 2 1 7 3 2 1 5 19 1 3 8 1 1 1 1 1 1 1 1 1
triple negative breast cancer	Official Title	PD-L1/CD274 PARP-1 HER2/ERBB2 Estrogen receptor alpha (ER alpha) collagen, type XI, alpha 2 3 more biomarker names Show less	2 1 1 1 1
triple negative breast cancer	Brief Summary	HER2/ERBB2 Estrogen receptor alpha (ER alpha) 5'-nucleotidase ecto 1 more biomarker names Show less	2 1 1
triplenegative breast cancer	Detailed Description	HER2/ERBB2	3
trophoblastic tumour	Eligibility Criteria	Luteinizing hormone (LH)	1
ureteral neoplasms	Detailed Description	Inducible T cell co-stimulator (ICOS)	1
ureteral neoplasms	Eligibility Criteria	PSA PD-L1/CD274 Luteinizing hormone (LH) 1 more biomarker names Show less	3 1 3
ureteral neoplasms	Official Title	Transforming growth factor-beta (TGF-beta) cytotoxic T-lymphocyte-associated protein 4	1 1
ureteral neoplasms	Outcome Measure	Transthyretin Thyroxine (T4) T-Cell differentiation antigen CD8 PD-L1/CD274 Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) Hydrocortisone GTP binding protein 1 glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 enhancer of mRNA decapping 4 Creatinine Creatine CD36 molecule (thrombospondin receptor) Cardiac Troponin I C-reactive protein (CRP) BNP Bilirubin 23 more biomarker names Show less	1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
urethral cancer	Outcome Measure	Transthyretin T-Cell differentiation antigen CD8 PD-L1/CD274 Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) GTP binding protein 1 glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 enhancer of mRNA decapping 4 CD36 molecule (thrombospondin receptor) 10 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1
urethral cancer	Arm Group Description	Creatinine	1
urethral cancer	Detailed Description	Inducible T cell co-stimulator (ICOS)	1
urethral cancer	Eligibility Criteria	PSA PD-L1/CD274 Luteinizing hormone (LH) 1 more biomarker names Show less	3 1 2
urethral cancer	Official Title	Transforming growth factor-beta (TGF-beta) cytotoxic T-lymphocyte-associated protein 4	1 1
urogenital cancer	Arm Group Label	Microsatellite Instable (MSI)	1
urogenital cancer	Outcome Measure	Transthyretin Thyroxine (T4) T-Cell differentiation antigen CD8 RPS6 PSA PD-L1/CD274 Interleukin-8 (IL-8) Interleukin-6 (IL-6) Interleukin-2 (IL-2) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) Interleukin-10 (IL-10) Interferon Gamma (IFNg) Interferon alpha (IFN-alpha) Hydrocortisone GTP binding protein 1 glycoprotein VI (platelet) glycoprotein V (platelet) glycoprotein 2 GINS complex subunit 2 GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 Fibroblast growth factor receptor 3 (FGFR3) Fanconi renotubular syndrome enhancer of mRNA decapping 4 cytokine inducible SH2-containing protein Creatinine Creatine CD36 molecule (thrombospondin receptor) Cardiac Troponin I C-reactive protein (CRP) BNP Bilirubin 34 more biomarker names Show less	1 1 2 1 1 7 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1
urogenital cancer	Brief Title	ARID1A	1
urogenital cancer	Arm Group Description	PD-L1/CD274 Microsatellite Instable (MSI) Creatinine ARID1A 2 more biomarker names Show less	1 2 1 1
urogenital cancer	Detailed Description	Tumor necrosis factor alpha (TNF-alpha) TSC1 trophoblast glycoprotein RPTOR independent companion of MTOR, complex 2 retinoblastoma 1 p16 mTOR Inducible T cell co-stimulator (ICOS) Fibroblast Growth Factor (FGF2) Cyclin E1 c-Myc BRCA1 ARID1A 11 more biomarker names Show less	1 1 1 1 1 1 1 1 1 1 1 1 1
urogenital cancer	Eligibility Criteria	UGT1A1 UDP glucuronosyltransferase family 1 member A8 UDP glucuronosyltransferase family 1 member A4 UDP glucuronosyltransferase family 1 member A10 UDP glucuronosyltransferase 1 family, polypeptide A7 UDP glucuronosyltransferase 1 family, polypeptide A6 trophoblast glycoprotein T-cell surface antigen CD4 solute carrier organic anion transporter family member 1B3 ROS1 retinoblastoma 1 PSA PD-L1/CD274 PD-1/CD279 p16 neuralized E3 ubiquitin protein ligase 1 N-Myc MYCL proto-oncogene mitogen-activated protein kinase kinase 7 MATE2 MATE1 Luteinizing hormone (LH) HER2/ERBB2 FSH Fibroblast growth factor receptor 3 (FGFR3) Epidermal growth factor receptor (EGFR) cytotoxic T-lymphocyte-associated protein 4 cytokine inducible SH2-containing protein Cytokeratin 20 Cytokeratin 18 Cyclin E1 CA125 ovarian cancer antigen (MUC16) c-Myc Butanone BRAF B-lymphocyte antigen CD20 Ataxia telangiectasia mutated ARID1A Anaplastic lymphoma receptor tyrosine kinase (ALP) Alkaline phosphatase (ALPL) 38 more biomarker names Show less	2 2 2 2 2 2 1 1 1 2 1 6 4 2 1 1 1 1 1 1 1 9 2 1 1 3 1 1 1 1 1 1 1 1 4 1 1 2 3 1
urogenital cancer	Official Title	XPA binding protein 2 Transforming growth factor-beta (TGF-beta) PD-L1/CD274 Interleukin-23 (IL-23) interleukin 37 cytotoxic T-lymphocyte-associated protein 4 crooked neck pre-mRNA splicing factor 1 ARID1A 6 more biomarker names Show less	1 1 1 1 1 2 1 1
uterine cancer	Arm Group Label	PARP-1	1

Drug Name	Biomarker Name	Biomarker Function
Durvalumab - Celgene/MedImmune		24,25-Dihydroxyvitamin D	Outcome Measure
	4E-BP1	Outcome Measure
	5'-nucleotidase ecto	Arm Group Description, Brief Summary, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	activator of HSP90 ATPase activity 1	Outcome Measure
	ADAM metallopeptidase domain 17	Arm Group Description, Arm Group Label, Brief Title, Official Title
	Adenosine diphosphate ribose	Detailed Description, Eligibility Criteria
	Alkaline phosphatase (ALPL)	Eligibility Criteria, Outcome Measure
	Alpha-fetoprotein (AFP)	Detailed Description, Eligibility Criteria, Outcome Measure
	ALT	Eligibility Criteria, Outcome Measure
	amelogenin, X-linked	Eligibility Criteria
	Anaplastic lymphoma receptor tyrosine kinase (ALP)	Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	Androgen Receptor (AR)	Arm Group Label
	annexin A6	Outcome Measure
	anthrax toxin receptor 1	Outcome Measure
	ARID1A	Brief Title, Detailed Description, Eligibility Criteria, Official Title
	artemin	Eligibility Criteria
	Ataxia telangiectasia mutated	Eligibility Criteria, Outcome Measure
	ATP binding cassette subfamily G member 2 (Junior blood group)	Eligibility Criteria
	ATPase inhibitory factor 1 (ATPI)	Eligibility Criteria
	ATR	Outcome Measure
	ATRX	Eligibility Criteria
	B-cell lymphoma 2 (Bcl-2)	Eligibility Criteria
	B-lymphocyte antigen CD19	Eligibility Criteria, Official Title, Outcome Measure
	B-lymphocyte antigen CD20	Eligibility Criteria, Outcome Measure
	Bcl-6	Eligibility Criteria
	betacellulin	Detailed Description
	Bilirubin	Eligibility Criteria, Outcome Measure
	BNP	Outcome Measure
	BRAF	Brief Summary, Detailed Description, Eligibility Criteria
	BRCA1	Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	BRCA1 associated RING domain 1	Eligibility Criteria
	BRCA1 interacting protein C-terminal helicase 1	Eligibility Criteria
	BRCA2	Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	Bruton's tyrosine kinase (BTK)	Official Title, Outcome Measure
	Butanone	Detailed Description, Eligibility Criteria
	Butyl nitrite	Eligibility Criteria
	C-C motif chemokine 5 (CCL5	Detailed Description
	C-Kit	Eligibility Criteria
	c-Met	Arm Group Description, Brief Summary, Eligibility Criteria, Outcome Measure
	c-Myc	Detailed Description, Eligibility Criteria, Outcome Measure
	C-reactive protein (CRP)	Outcome Measure
	C-X-C motif chemokine ligand 11	Detailed Description
	CA 15-3	Eligibility Criteria
	CA125 ovarian cancer antigen (MUC16)	Eligibility Criteria, Outcome Measure
	Carbohydrate antigen 19-9 (CA 19-9)	Detailed Description, Eligibility Criteria, Outcome Measure
	carcinoembryonic antigen related cell adhesion molecule 3	Detailed Description, Eligibility Criteria
	Cardiac Troponin I	Detailed Description, Eligibility Criteria, Outcome Measure
	Caspase-3 (CASP3)	Outcome Measure
	CCL17	Outcome Measure
	CD161 (NKRP1)	Outcome Measure
	CD163	Outcome Measure
	CD177 molecule	Arm Group Description
	CD25 (IL2RA)	Detailed Description
	CD3 gamma chain (CD3G)	Detailed Description, Outcome Measure
	CD33 molecule	Outcome Measure
	CD36 molecule (thrombospondin receptor)	Outcome Measure
	CD38	Outcome Measure
	CD69	Outcome Measure
	CD80 molecule	Arm Group Description, Detailed Description
	CD82 molecule	Arm Group Description
	CDC20	Outcome Measure
	CDK6	Arm Group Description
	CDKN1B	Outcome Measure
	CEA	Detailed Description, Eligibility Criteria
	cell division cycle 25C	Outcome Measure
	centromere protein J	Brief Summary
	CEP55	Outcome Measure
	CGA	Eligibility Criteria
	chaperonin containing TCP1 subunit 3	Eligibility Criteria
	Chemokine IFN-Î³-inducible protein 10 (IP-10/CXCL10)	Detailed Description, Outcome Measure
	CHK1	Eligibility Criteria
	CHK2	Eligibility Criteria
	Cholangitis, primary sclerosing	Brief Summary, Detailed Description
	chorionic gonadotropin beta subunit 5	Eligibility Criteria
	cleavage and polyadenylation specific factor 4	Outcome Measure
	Cobalamin	Arm Group Description
	collagen, type XI, alpha 2	Eligibility Criteria, Official Title, Outcome Measure
	Colony stimulating factor 1 receptor (CSF1R)	Brief Title, Official Title, Outcome Measure
	Creatine	Eligibility Criteria, Outcome Measure
	Creatinine	Arm Group Description, Eligibility Criteria, Outcome Measure
	CRK proto-oncogene, adaptor protein	Outcome Measure
	crooked neck pre-mRNA splicing factor 1	Official Title
	CXCL13	Detailed Description, Outcome Measure
	CXCL9	Detailed Description, Outcome Measure
	CXCR4	Official Title, Outcome Measure
	Cyanocobalamin	Arm Group Description
	Cyclin B1	Outcome Measure
	Cyclin D1	Arm Group Description, Detailed Description
	Cyclin D2	Arm Group Description, Detailed Description
	Cyclin D3	Arm Group Description, Detailed Description
	Cyclin E1	Detailed Description, Eligibility Criteria
	cyclin-dependent kinase 12	Arm Group Description, Detailed Description, Eligibility Criteria
	Cyclin-dependent kinase 4 (CDK4)	Arm Group Description, Detailed Description, Eligibility Criteria
	CYP3A4	Eligibility Criteria
	Cystatin C	Eligibility Criteria
	cytochrome P450 family 2 subfamily B member 6	Eligibility Criteria
	Cytokeratin 18	Eligibility Criteria
	Cytokeratin 20	Eligibility Criteria, Outcome Measure
	Cytokeratin 5	Eligibility Criteria
	cytokine inducible SH2-containing protein	Brief Summary, Eligibility Criteria, Outcome Measure
	cytoskeleton-associated protein 4	Eligibility Criteria
	cytotoxic T-lymphocyte-associated protein 4	Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	D-threo-Isocitric acid	Eligibility Criteria
	D-Tryptophan	Outcome Measure
	dicer 1, ribonuclease type III	Eligibility Criteria, Official Title
	discoidin domain receptor tyrosine kinase 1	Eligibility Criteria, Outcome Measure
	DNA (cytosine-5-)-methyltransferase 3 beta	Eligibility Criteria
	DNA polymerase delta 2, accessory subunit	Eligibility Criteria
	DNA polymerase delta interacting protein 2	Outcome Measure
	DNA repair protein XRCC1	Outcome Measure
	Down syndrome chromosome region	Outcome Measure
	DPYD	Eligibility Criteria
	dynactin subunit 6	Outcome Measure
	EML4	Eligibility Criteria
	enhancer of mRNA decapping 4	Outcome Measure
	Epidermal growth factor receptor (EGFR)	Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	Epithelial cell adhesion molecule (EpCAM)	Outcome Measure
	ERCC1	Outcome Measure
	Erythropoietin (EPO)	Eligibility Criteria
	Estradiol-17beta 3-sulfate	Eligibility Criteria
	Estrogen receptor alpha (ER alpha)	Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	Ethenyl acetate	Eligibility Criteria
	family with sequence similarity 175, member A	Eligibility Criteria
	FANCA	Eligibility Criteria
	FANCB	Eligibility Criteria
	Fanconi anemia, complementation group L	Eligibility Criteria
	Fanconi renotubular syndrome	Outcome Measure
	Fc fragment of IgG receptor Ib	Eligibility Criteria
	Fc fragment of IgG, low affinity IIIb, receptor (CD16b)	Outcome Measure
	Fc gamma RIIIa	Outcome Measure
	Fibroblast Growth Factor (FGF2)	Detailed Description
	Fibroblast growth factor receptor 1 (FGFR1)	Arm Group Description, Detailed Description, Eligibility Criteria
	Fibroblast growth factor receptor 2 (FGFR2)	Arm Group Description, Detailed Description
	Fibroblast growth factor receptor 3 (FGFR3)	Arm Group Description, Detailed Description, Eligibility Criteria, Outcome Measure
	Fibroblast growth factor receptor 4 (FGFR4)	Arm Group Description, Detailed Description
	folate receptor	Brief Title, Official Title
	Folic acid	Arm Group Description
	Folinic acid	Arm Group Description
	FOXP3	Detailed Description, Outcome Measure
	FSH	Eligibility Criteria
	gamma-glutamyltransferase 2	Eligibility Criteria, Outcome Measure
	gamma-glutamyltransferase light chain 1	Eligibility Criteria, Outcome Measure
	gamma-glutamyltransferase light chain 3	Eligibility Criteria, Outcome Measure
	GEN1, Holliday junction 5' flap endonuclease	Eligibility Criteria
	general transcription factor IIH, polypeptide 5	Outcome Measure
	GGT	Eligibility Criteria, Outcome Measure
	GGTLC4P	Eligibility Criteria, Outcome Measure
	GGTLC5P	Eligibility Criteria, Outcome Measure
	GINS complex subunit 2	Outcome Measure
	glutaryl-CoA dehydrogenase	Detailed Description
	glycoprotein 2	Outcome Measure
	glycoprotein V (platelet)	Outcome Measure
	glycoprotein VI (platelet)	Outcome Measure
	glycosylated serum albumin	Eligibility Criteria
	Gonadotropin releasing hormone	Eligibility Criteria
	gonadotropin releasing hormone 1	Eligibility Criteria
	gp100	Outcome Measure
	Granulocyte-macrophage colony-stimulating factor (GM-CSF)	Arm Group Description, Brief Title, Official Title, Outcome Measure
	granzyme A	Outcome Measure
	growth differentiation factor 1	Eligibility Criteria
	GSTP-1	Outcome Measure
	GTP binding protein 1	Outcome Measure
	GUCY2EP	Detailed Description
	Gut Microbiome	Brief Title, Official Title
	GZMB	Outcome Measure
	H3P10	Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	H3P23	Outcome Measure
	HAVCR2 (TIM-3)	Detailed Description
	Hematopoietic progenitor cell antigen CD34	Eligibility Criteria
	HER2/ERBB2	Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	HLA-A	Eligibility Criteria, Outcome Measure
	HPV E6	Detailed Description, Outcome Measure
	Human Microbiome	Arm Group Description, Brief Title, Official Title
	Hydrocortisone	Outcome Measure
	hypertrichosis 2 (generalized, congenital)	Eligibility Criteria
	IDH1	Brief Summary, Detailed Description, Eligibility Criteria
	IDH2	Brief Summary, Detailed Description, Eligibility Criteria
	IGF1	Detailed Description
	immunoglobulin heavy constant mu	Outcome Measure
	Indoleamine 2, 3-dioxygenase 1 (IDO1)	Outcome Measure
	Inducible T cell co-stimulator (ICOS)	Detailed Description, Outcome Measure
	Inhibin A	Eligibility Criteria
	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma	Eligibility Criteria
	Insulin	Detailed Description, Eligibility Criteria
	integrin subunit alpha E	Outcome Measure
	Interferon alpha (IFN-alpha)	Outcome Measure
	Interferon Gamma (IFNg)	Arm Group Description, Detailed Description, Eligibility Criteria, Outcome Measure
	Interleukin 1 Beta (IL-1Î²)	Outcome Measure
	interleukin 11	Outcome Measure
	interleukin 34	Outcome Measure
	interleukin 37	Official Title
	interleukin 7 receptor	Detailed Description
	Interleukin-10 (IL-10)	Outcome Measure
	Interleukin-12A (IL-12p35)	Arm Group Description, Outcome Measure
	Interleukin-12B (IL-12p40)	Arm Group Description, Outcome Measure
	Interleukin-13 (IL-13)	Outcome Measure
	Interleukin-17 (IL-17)	Outcome Measure
	Interleukin-2 (IL-2)	Outcome Measure
	Interleukin-23 (IL-23)	Official Title
	Interleukin-3 (IL-3)	Outcome Measure
	Interleukin-4 (IL-4)	Outcome Measure
	Interleukin-5 (IL-5)	Outcome Measure
	Interleukin-6 (IL-6)	Outcome Measure
	Interleukin-8 (IL-8)	Outcome Measure
	Interleukin-9 (IL-9)	Outcome Measure
	iroquois homeobox 2	Arm Group Description, Brief Title, Official Title
	Isocitric acid	Brief Summary
	IVD	Outcome Measure
	KLRC1	Outcome Measure
	KRAS	Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title
	Kynurenine	Outcome Measure
	L-Aspartic acid	Eligibility Criteria, Outcome Measure
	L-selectin	Detailed Description
	L-Tryptophan	Outcome Measure
	Lactate dehydrogenase (LDH)	Outcome Measure
	LAG-3 (CD223)	Detailed Description, Outcome Measure
	LARGE xylosyl and glucuronyltransferase 1	Official Title
	lipase, member I	Brief Summary
	lipoic acid synthetase	Brief Summary
	LOC102724197	Eligibility Criteria, Outcome Measure
	long intergenic non-protein coding RNA 1194	Outcome Measure
	Luteinizing hormone (LH)	Eligibility Criteria
	LY75-CD302 readthrough	Outcome Measure
	lymphocyte antigen 75	Outcome Measure
	Mab-21 domain containing 1	Outcome Measure
	Macrophage antigen CD68	Outcome Measure
	Macrophage colony stimulating factor (MCSF)	Arm Group Description, Outcome Measure
	macrophage scavenger receptor 1	Outcome Measure
	major histocompatibility complex, class I, C	Detailed Description
	mannose receptor, C type 1	Brief Summary, Detailed Description, Eligibility Criteria
	mannosidase alpha class 2C member 1	Outcome Measure
	MAPK1	Outcome Measure
	MATE1	Eligibility Criteria
	MATE2	Eligibility Criteria
	matrix metallopeptidase 7	Outcome Measure
	MDM2	Detailed Description, Official Title
	MDR1	Eligibility Criteria
	MEK1	Official Title
	methylmalonic aciduria (cobalamin deficiency) cblB type	Outcome Measure
	MGMT	Arm Group Description
	MHC class I antigen HLA-A heavy chain (HLA-A)	Eligibility Criteria, Outcome Measure
	Microsatellite Instable (MSI)	Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title
	Microsatellite Stable (MSS)	Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title
	mitogen-activated protein kinase 14	Outcome Measure
	mitogen-activated protein kinase kinase 7	Detailed Description, Eligibility Criteria
	MLH1	Eligibility Criteria
	MLH3	Eligibility Criteria
	MMP9	Outcome Measure
	Monocyte chemoattractant protein-1 (MCP-1/CCL2)	Outcome Measure
	Monocyte differentiation antigen CD14	Outcome Measure
	MRE11	Eligibility Criteria
	MSH2	Eligibility Criteria
	MSH3	Eligibility Criteria
	MSH6	Eligibility Criteria
	mTOR	Detailed Description
	MXLPO	Eligibility Criteria
	MYCL proto-oncogene	Eligibility Criteria
	N-Myc	Eligibility Criteria
	NDC80	Outcome Measure
	Neprilysin	Brief Title
	neuralized E3 ubiquitin protein ligase 1	Eligibility Criteria
	Neuron-specific enolase (NSE)	Detailed Description, Outcome Measure
	Nibrin	Eligibility Criteria
	NK2 homeobox 1	Eligibility Criteria
	NKG2D (KLRK1)	Outcome Measure
	Nuclear protein Ki67	Detailed Description, Eligibility Criteria, Outcome Measure
	nuclear protein, ataxia-telangiectasia locus	Eligibility Criteria
	NUF2	Outcome Measure
	OCT1	Eligibility Criteria
	OCT2	Eligibility Criteria
	p16	Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	p53 (tumor protein p53)	Arm Group Description, Detailed Description, Eligibility Criteria, Outcome Measure
	p63	Detailed Description, Eligibility Criteria
	PAI-1	Outcome Measure
	Pancreatic lipase	Detailed Description
	papillary renal cell carcinoma (translocation-associated)	Brief Summary, Brief Title, Detailed Description, Eligibility Criteria
	PARP-1	Arm Group Label, Eligibility Criteria, Official Title, Outcome Measure
	partner and localizer of BRCA2	Eligibility Criteria
	PCNA	Outcome Measure
	PD-1/CD279	Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	PD-L1/CD274	Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
	PD-L2	Eligibility Criteria, Outcome Measure
	PDGFRA	Arm Group Description
	PDGFRB	Arm Group Description
	PGR	Detailed Description, Eligibility Criteria
	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta	Detailed Description, Eligibility Criteria
	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma	Detailed Description, Eligibility Criteria
	phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha	Eligibility Criteria
	Phosphatidylinositols	Detailed Description
	PIK3CA	Arm Group Description, Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	PIK3CD	Detailed Description, Eligibility Criteria
	PLK4	Arm Group Label
	PML-RARA fusion	Eligibility Criteria
	PMS1	Eligibility Criteria
	PMS2	Eligibility Criteria
	polymerase (DNA directed), delta 1, catalytic subunit	Eligibility Criteria
	potassium channel, two pore domain subfamily K, member 3	Eligibility Criteria
	POU class 2 homeobox 2	Eligibility Criteria
	PPP1R13L	Eligibility Criteria
	pregnancy specific beta-1-glycoprotein 2	Detailed Description, Eligibility Criteria
	Pro-opiomelanocortin (POMC	Detailed Description, Eligibility Criteria
	Progesterone	Eligibility Criteria
	prostaglandin I2 (prostacyclin) receptor (IP)	Eligibility Criteria
	proteasome 26S subunit, non-ATPase 9	Outcome Measure
	protein phosphatase 2 regulatory subunit Balpha	Eligibility Criteria
	protein phosphatase 2, regulatory subunit A, alpha	Detailed Description, Eligibility Criteria
	PSA	Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	PTEN	Arm Group Description, Brief Summary, Eligibility Criteria
	PTTG1	Outcome Measure
	RAC-alpha serine/threonine-protein kinase (AKT)	Detailed Description
	RAD50	Outcome Measure
	RAD51	Outcome Measure
	RAD51 paralog B	Eligibility Criteria
	RAD51 paralog C	Arm Group Description, Eligibility Criteria, Outcome Measure
	RAD51 paralog D	Eligibility Criteria
	RAD54L	Eligibility Criteria
	RAS	Eligibility Criteria
	Ras protein specific guanine nucleotide releasing factor 1	Outcome Measure
	receptor accessory protein 5	Eligibility Criteria
	replication protein A2	Outcome Measure
	RET	Arm Group Description, Brief Summary, Eligibility Criteria, Official Title
	retinal pigment epithelium-specific protein 65kDa	Eligibility Criteria
	retinoblastoma 1	Detailed Description, Eligibility Criteria
	ribonuclease/angiogenin inhibitor 1	Eligibility Criteria
	ROS1	Arm Group Label, Eligibility Criteria
	RPS6	Outcome Measure
	RPTOR independent companion of MTOR, complex 2	Detailed Description
	RRM2	Outcome Measure
	Russell Silver syndrome	Outcome Measure
	schlafen family member 11	Detailed Description
	serine/threonine kinase 11 interacting protein	Brief Summary
	SERPINA2	Outcome Measure
	Serum albumin	Eligibility Criteria
	SET binding protein 1	Outcome Measure
	SHC adaptor protein 3	Eligibility Criteria
	sideroflexin 1	Eligibility Criteria
	Sjogren syndrome/scleroderma autoantigen 1	Outcome Measure
	SLC7A5	Eligibility Criteria
	SLCO1B1	Eligibility Criteria
	SMAD4	Outcome Measure
	solute carrier family 22 member 6	Eligibility Criteria
	solute carrier organic anion transporter family member 1B3	Eligibility Criteria
	somatostatin	Eligibility Criteria
	spermine synthase	Outcome Measure
	STAT3	Detailed Description, Official Title, Outcome Measure
	succinate dehydrogenase complex, subunit B, iron sulfur (Ip)	Eligibility Criteria
	suppressor of cytokine signaling 5	Eligibility Criteria
	Survivin	Outcome Measure
	T-Cell differentiation antigen CD8	Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	T-cell immunoreceptor with Ig and ITIM domains	Outcome Measure
	T-cell receptor CD3-epsilon (CD3e)	Detailed Description, Outcome Measure
	T-cell receptor T3 delta chain (CD3d)	Detailed Description, Outcome Measure
	T-cell surface antigen CD4	Detailed Description, Eligibility Criteria, Outcome Measure
	TCEAL1	Outcome Measure
	teneurin transmembrane protein 1	Detailed Description
	TERT	Detailed Description, Outcome Measure
	testis and ovary specific PAZ domain containing 1	Brief Title
	Testosterone	Eligibility Criteria, Outcome Measure
	TGFBR1	Eligibility Criteria
	Thymidine	Brief Title, Official Title
	Thymidylate synthetase	Outcome Measure
	Thyroid stimulating hormone beta (TSH)	Detailed Description, Eligibility Criteria, Outcome Measure
	Thyroxine (T4)	Eligibility Criteria, Outcome Measure
	Toll-Like Receptor 4 (TLR4)	Official Title
	Transforming growth factor-beta (TGF-beta)	Official Title, Outcome Measure
	transmembrane p24 trafficking protein 7	Outcome Measure
	Transthyretin	Outcome Measure
	trophoblast glycoprotein	Detailed Description, Eligibility Criteria
	TSC1	Detailed Description
	TSPYL2	Brief Title, Eligibility Criteria, Official Title, Outcome Measure
	TTF1	Eligibility Criteria
	tubulin folding cofactor E	Detailed Description, Eligibility Criteria, Outcome Measure
	Tumor Mutational Burden	Arm Group Description, Arm Group Label, Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
	Tumor necrosis factor alpha (TNF-alpha)	Detailed Description, Eligibility Criteria, Outcome Measure
	tumor necrosis factor receptor superfamily member 9	Detailed Description
	tumor necrosis factor receptor superfamily, member 4	Arm Group Description, Outcome Measure
	tumor protein p53 binding protein 1	Outcome Measure
	tumor-associated calcium signal transducer 2	Eligibility Criteria, Outcome Measure
	UBE2C	Outcome Measure
	ubiquitin associated and SH3 domain containing B	Outcome Measure
	UDP glucuronosyltransferase 1 family, polypeptide A6	Eligibility Criteria
	UDP glucuronosyltransferase 1 family, polypeptide A7	Eligibility Criteria
	UDP glucuronosyltransferase family 1 member A10	Eligibility Criteria
	UDP glucuronosyltransferase family 1 member A4	Eligibility Criteria
	UDP glucuronosyltransferase family 1 member A8	Eligibility Criteria
	UGT1A1	Eligibility Criteria
	Uric acid	Outcome Measure
	Uridine 5'-diphosphate	Eligibility Criteria
	UV radiation resistance associated	Eligibility Criteria
	Vascular endothelial growth factor A (VEGF)	Eligibility Criteria, Outcome Measure
	VEGFR	Arm Group Description, Eligibility Criteria
	VEGFR1	Arm Group Description
	WEE1	Arm Group Label
	WT1	Eligibility Criteria
	XPA binding protein 2	Official Title
	XPD	Outcome Measure
	XRCC2	Eligibility Criteria

Indication	Phase 0	Phase I	Phase II	Phase III	Phase IV
Skin cancer	2	7	15	1	24
Renal cell carcinoma	-	4	12	2	8
Bladder cancer	1	6	34	10	5
Autoimmune disorders	-	-	-	-	1
Hepatoblastoma	-	1	-	-	-
Thyroid cancer	1	1	2	-	-
Germ cell cancer	-	-	2	-	-
Triple negative breast cancer	-	4	23	3	-
Adrenocortical carcinoma	-	1	1	-	-
Merkel cell carcinoma	-	-	4	1	1
Adenocarcinoma	-	20	143	12	49
Large cell carcinoma	-	1	6	-	1
Neuroblastoma	-	-	1	-	-
Chordoma	-	-	1	-	-
Mesothelioma	-	1	10	1	7
Squamous cell cancer	2	18	87	10	35
Solid tumours	-	27	44	1	5
Colon cancer	-	-	3	-	3
Ewing's sarcoma	-	-	1	-	-
Peritoneal cancer	-	3	18	1	-
Salivary gland cancer	-	-	3	-	-
Hypopharyngeal cancer	-	3	4	3	-
Neurofibrosarcoma	-	-	1	-	-
Synovial sarcoma	-	1	2	-	-
Meningeal carcinomatosis	-	-	-	-	1
Gastrointestinal stromal tumours	-	-	1	-	-
Mediastinal disorders	-	-	-	-	1
Nervous system neoplasms	-	1	-	-	-
Gynaecological cancer	-	10	47	5	6
Seminoma	-	-	1	-	-
Uveal melanoma	-	-	2	-	-
Endocrine gland neoplasms	-	1	2	-	1
Uterine cancer	-	6	24	4	3
Urethral cancer	1	-	7	3	-
Male breast cancer	-	4	16	2	-
Pharyngeal neoplasms	-	-	1	-	-
Guillain-Barre syndrome	-	-	-	-	1
Myelofibrosis	-	1	-	-	-
Adenosquamous carcinoma	-	-	1	1	2
Head and neck cancer	1	18	71	7	14
Oligodendroglioma	-	-	1	-	-
Bone metastases	-	-	-	-	1
Advanced breast cancer	2	13	42	3	2
Pancreatic cancer	-	10	44	-	2
B-cell lymphoma	-	7	11	-	1
Endocrine disorders	1	12	46	-	3
Sarcoma	-	5	22	4	5
Oropharyngeal cancer	1	4	12	3	-
Brain metastases	-	1	12	4	1
Pelvic cancer	1	23	119	15	15
Hodgkin's disease	-	-	2	-	6
Soft tissue sarcoma	-	3	14	1	3
Colitis	-	-	-	-	2
Lymphoma	1	9	17	-	8
Rhabdomyosarcoma	-	1	1	-	-
Early breast cancer	2	1	15	2	-
Rectal cancer	-	3	13	-	4
Prostate cancer	-	-	21	-	1
Liver metastases	-	3	3	-	3
Malignant thymoma	-	-	-	-	1
Haematological malignancies	1	11	23	-	10
Non-Hodgkin's lymphoma	1	8	15	-	2
Malignant fibrous histiocytoma	-	-	5	-	-
Malignant melanoma	1	5	12	1	20
Appendiceal cancer	-	-	2	-	-
Mouth neoplasm	1	3	6	3	-
Mantle-cell lymphoma	-	1	1	-	-
Infusion related reaction	-	-	-	-	1
Haemangioendothelioma	-	-	1	-	-
Vulvovaginal cancer	-	3	1	-	-
Adrenal cancer	-	1	2	-	-
Anaplastic large cell lymphoma	-	-	1	-	-
HER2 positive breast cancer	-	-	5	-	-
Cutaneous T-cell lymphoma	1	-	2	-	-
Fallopian tube cancer	-	3	19	1	-
Gallbladder cancer	-	1	13	4	1
Sezary syndrome	-	-	1	-	-
Myelodysplastic syndromes	-	1	2	-	-
Anal cancer	-	2	7	-	2
Periampullary cancer	-	-	2	-	-
Small cell lung cancer	-	8	42	6	17
Leiomyosarcoma	-	-	4	-	-
Basal cell cancer	-	-	1	-	-
Glioma	-	1	6	-	3
Ureteral neoplasms	1	-	6	3	1
Dysgerminoma	-	-	1	-	-
Glandular and epithelial neoplasms	1	32	202	26	55
CNS cancer	-	3	7	-	7
Acute myeloid leukaemia	-	-	1	-	-
Cardiovascular disorders	-	-	3	-	1
Renal cancer	1	4	19	7	15
Thoracic neoplasms	2	29	170	38	170
Nasopharyngeal cancer	-	1	4	-	-
Ependymoma	-	1	-	-	-
Arthritis	-	-	-	-	1
Inflammatory breast cancer	-	-	1	-	-
Colorectal cancer	-	10	42	-	6
Gastric cancer	-	4	24	1	4
Peripheral T-cell lymphoma	-	-	2	-	-
Plasmablastic lymphoma	-	-	1	-	-
Ductal carcinoma	-	1	3	-	-
Laryngeal cancer	1	3	7	3	-
Lung cancer	2	29	170	38	169
Haemangiosarcoma	-	-	3	-	-
Non-small cell lung cancer	2	23	125	29	140
Duodenal cancer	-	-	2	-	1
Interstitial lung diseases	-	-	-	-	1
Liver cancer	-	5	41	7	10
Astrocytoma	-	1	6	-	3
Breast cancer	2	13	53	4	4
Diffuse intrinsic pontine glioma	-	1	-	-	-
Endometrial cancer	-	1	16	3	2
Mycosis fungoides	-	-	1	-	-
Plasmacytoma	-	1	1	-	-
Pulmonary blastoma	-	-	2	-	-
Multiple myeloma	-	2	5	-	-
Adenoid cystic carcinoma	-	-	1	-	-
Liposarcoma	-	-	3	-	1
Glioblastoma	-	1	6	-	3
Cholangiocarcinoma	-	2	30	4	2
Cervical cancer	-	6	11	1	1
Neuroendocrine tumours	-	2	12	2	3
Bone cancer	-	1	4	-	1
Diffuse large B cell lymphoma	-	7	9	-	-
Kaposi's sarcoma	-	-	1	-	1
Gastrointestinal cancer	-	16	72	2	15
Malignant-mesothelioma	-	1	6	1	1
Leukaemia	-	-	3	-	1
Myeloma	-	2	5	-	1
Osteosarcoma	-	1	4	-	-
Giant cell tumours	-	-	2	-	-
Cancer	9	100	500	75	204
Clear cell sarcoma	-	-	1	-	-
Ovarian cancer	-	6	32	1	2
Cancer metastases	-	4	17	4	4
Neuroendocrine carcinoma	-	1	9	2	1
Hepatitis B	-	-	2	-	-
Oesophageal cancer	-	6	29	2	3
Alveolar soft part sarcoma	-	-	2	-	-
Carcinoma	1	32	198	26	54
Penile cancer	-	-	1	-	-
Biliary cancer	-	3	38	4	4
Urogenital cancer	1	19	100	19	28
Trophoblastic tumour	-	-	1	-	-
T-cell lymphoma	1	-	4	-	-
Carcinoid tumour	-	-	1	-	-
Follicular lymphoma	-	2	4	-	-
Kidney-neoplasms	-	-	-	-	1
HER2 negative breast cancer	1	2	11	1	-
Brain cancer	-	1	6	-	4
Chronic lymphocytic leukaemia	-	-	2	-	-

Indication	Qualifier	Patient Segment	Phase	Countries	Route / Formulation	Developers	Event Date
Acute myeloid leukaemia	-	Combination therapy, Newly diagnosed	Phase II	Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Portugal, Spain, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 Jun 2016
Biliary cancer	in combination with gemcitabine and cisplatin	Combination therapy, Late-stage disease	Registered	USA	IV / Infusion	AstraZeneca	02 Sep 2022
Biliary cancer	In combination with gemcitabine plus cisplatin	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Recurrent	Registered	European Union, Iceland, Japan, Liechtenstein, Norway	IV / Infusion	AstraZeneca	28 Dec 2022
Biliary cancer	In combination with gemcitabine plus cisplatin	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Recurrent	Preregistration	Australia, Brazil, Canada, Israel, Singapore, Switzerland, United Kingdom	IV / Infusion	AstraZeneca	05 Sep 2022
Biliary cancer	In combination with gemcitabine plus cisplatin	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Recurrent	Phase III	Argentina, Chile, China, Hong Kong, India, Russia, South Korea, Taiwan, Thailand	IV / Infusion	AstraZeneca	16 Apr 2019
Biliary cancer	in combination with gemcitabine-based chemotherapy regimens	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase III	South Korea	IV / Infusion	AstraZeneca	16 Aug 2023
Bladder cancer	in combination with Bacillus Calmette-Guerin (BCG)	Combination therapy, First-line therapy	Phase III	USA	IV / Infusion	AstraZeneca	23 Aug 2023
Bladder cancer	-	Adjuvant therapy, First-line therapy, Monotherapy	Phase III	Australia, Brazil, Canada, Chile, Czech Republic, France, Israel, Japan, Netherlands, Philippines, Poland, Russia, South Korea, Taiwan, Turkey, USA, Vietnam	IV / Infusion	AstraZeneca	16 Nov 2018
Bladder cancer	-	Combination therapy, Neoadjuvant therapy	Phase III	USA	IV / Infusion	AstraZeneca	05 Aug 2021
Bladder cancer	-	Combination therapy, First-line therapy, Neoadjuvant therapy	Phase III	Australia, Brazil, Canada, Chile, Czech Republic, France, Israel, Japan, Netherlands, Philippines, Poland, Russia, South Korea, Taiwan, Turkey, USA, Vietnam	IV / Infusion	AstraZeneca	16 Nov 2018
Bladder cancer	-	Combination therapy	Phase III	Australia, Japan, Netherlands, Russia, Spain, United Kingdom	IV / Infusion	AstraZeneca	14 May 2018
Bladder cancer	in combination with olaparib	Combination therapy, Late-stage disease, Neoadjuvant therapy	Phase II	Spain	IV / Infusion	AstraZeneca, Spanish Oncology Genito-Urinary Group	16 Nov 2018
Bladder cancer	-	Combination therapy, First-line therapy, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	Canada, Russia, South Korea, Spain, Taiwan, USA, Vietnam	IV / Infusion	AstraZeneca	16 Mar 2018
Bladder cancer	-	Combination therapy, Neoadjuvant therapy, Second-line therapy or greater	Phase II	Switzerland	IV / unspecified	AstraZeneca	15 Jul 2018
Bladder cancer	-	Adjuvant therapy	Phase II	Canada	IV / Infusion	AstraZeneca, Canadian Cancer Trials Group	21 Dec 2018
Bladder cancer	with Oleclumab	Combination therapy, In adults, In the elderly, Neoadjuvant therapy	No development reported (I)	USA	IV / unspecified	AstraZeneca	28 Aug 2022
Bladder cancer	-	In adults, In the elderly, Monotherapy, Neoadjuvant therapy	No development reported (I)	USA	IV / unspecified	AstraZeneca	28 Aug 2022
Brain metastases	-	Second-line therapy or greater	Phase II	USA	IV / Infusion	Washington University School of Medicine	01 Sep 2016
Breast cancer	-	Adjuvant therapy, Late-stage disease	Phase II	United Kingdom	IV / Infusion	AstraZeneca	18 Apr 2019
Breast cancer	Triple negative breast cancer; in combination with CFI 400945	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Canada	IV / Infusion	AstraZeneca, University Health Network, Canadian Cancer Trials Group	19 Dec 2019
Breast cancer	-	Adjunctive treatment, Early-stage disease, Neoadjuvant therapy	Phase II	Germany	IV / Infusion	AstraZeneca, Celgene International SARL	08 Mar 2016
Breast cancer	-	Combination therapy, Neoadjuvant therapy	Phase II	Belgium	IV / Injection	AstraZeneca, Jules Bordet Institute	20 Sep 2019
Breast cancer	Hormone-receptor-positive breast cancer	Combination therapy, Neoadjuvant therapy	Phase II	USA	IV / Infusion	AstraZeneca	26 Apr 2019
Breast cancer	-	Late-stage disease, Neoadjuvant therapy	Phase II	United Kingdom	IV / Infusion	AstraZeneca	18 Apr 2019
Breast cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, MedImmune, Gradalis	07 Sep 2016
Breast cancer	Triple negative	First-line therapy	Phase II	France	IV / Infusion	AstraZeneca, Gustave Roussy	06 Dec 2021
Breast cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	South Korea	IV / Infusion	Yonsei University College of Medicine	07 Dec 2016
Breast cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase I/II	South Korea	IV / Infusion	AstraZeneca	28 Dec 2020
Breast cancer	-	Combination therapy, First-line therapy, Metastatic disease	Phase I/II	Canada, Poland, South Korea, Taiwan, USA, United Kingdom	IV / Infusion	AstraZeneca	21 Dec 2018
Breast cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	South Korea	IV / Infusion	AstraZeneca	28 Dec 2020
Breast cancer	-	Combination therapy, Late-stage disease, Neoadjuvant therapy	Phase I/II	Belgium	IV / Infusion	Grand Hopital de Charleroi	01 Feb 2017
Breast cancer	-	Combination therapy, Neoadjuvant therapy, Newly diagnosed	Phase I/II	USA	IV / Infusion	Yale University	01 Nov 2015
Breast cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase I/II	Australia, Brazil, Canada, France, Germany, India, Italy, Poland, Russia, Spain, Taiwan, Turkey, USA, United Kingdom	IV / Infusion	AstraZeneca, Daiichi Sankyo Company	28 Dec 2020
Breast cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	Australia, Brazil, France, Germany, India, Italy, Poland, Russia, Spain, Taiwan, USA, United Kingdom	IV / Infusion	AstraZeneca, Daiichi Sankyo Company	28 Dec 2020
Breast cancer	in combination with paclitaxel, in patients with metastatic triple negative PD-L1 positive breast cancer	Combination therapy, Second-line therapy or greater	Phase I/II	Saudi Arabia	IV / Infusion	AstraZeneca	01 Jul 2016
Breast cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I	Belgium, Mexico	IV / Infusion	AstraZeneca, Daiichi Sankyo Company	17 Dec 2020
Breast cancer	-	Combination therapy, Second-line therapy or greater	No development reported (I)	USA	IV / Infusion	MedImmune, Washington University School of Medicine	28 Aug 2022
Breast cancer	-	Adjunctive treatment, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater	No development reported (I)	Canada	IV / Infusion	AstraZeneca	28 Dec 2019
Breast cancer	-	Monotherapy, Second-line therapy or greater	No development reported (I)	USA	IV / Infusion	MedImmune, Washington University School of Medicine	28 Aug 2022
CNS cancer	-	In adolescents, In children, In infants, Second-line therapy or greater, Treatment-resistant	No development reported (I)	USA	IV / Infusion	Childrens Hospital Los Angeles	28 Dec 2019
Cervical cancer	-	First-line therapy, In adults, In the elderly, Late-stage disease	Phase III	Brazil, Chile, China, Hungary, India, Japan, Mexico, Philippines, Poland, Russia, South Africa, South Korea, Taiwan	IV / Infusion	AstraZeneca	15 Feb 2019
Cervical cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Cervical cancer	-	Adjunctive treatment, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	02 Aug 2020
Cervical cancer	in combination with axalimogene filolisbac	Combination therapy, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	MedImmune, Undisclosed	01 Apr 2015
Cervical cancer	-	-	No development reported (I)	Netherlands	IV / Infusion	AstraZeneca, MedImmune	28 Aug 2022
Cholangiocarcinoma	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	Germany	IV / Infusion	AIO Studien gGmbH, AstraZeneca	02 May 2018
Cholangiocarcinoma	-	Combination therapy, Late-stage disease	No development reported (I)	USA	IV / Infusion	National Cancer Institute (USA), University of Southern California	28 Aug 2022
Chronic lymphocytic leukaemia	-	Combination therapy, Monotherapy, Second-line therapy or greater	Phase I/II	France, Italy, Japan, Netherlands, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 May 2016
Chronic lymphocytic leukaemia	-	Combination therapy, Second-line therapy or greater	Phase I/II	France, Germany, Italy, Japan, Netherlands, USA, United Kingdom	IV / Infusion	Celgene Corporation	11 May 2016
Chronic lymphocytic leukaemia	-	Monotherapy, Second-line therapy or greater	Phase I/II	Germany	IV / Infusion	Celgene Corporation	11 May 2016
Colorectal cancer	capecitabine plus concomitant radiation therapy followed by durvalumab	First-line therapy, Neoadjuvant therapy	Phase II	Italy	IV / Infusion	AstraZeneca, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori	01 Jan 2020
Colorectal cancer	with tremelimumab for treatment of cancer with microsatellite instability (MSI) and microsatellite stability (MSS)no	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	Spain	IV / Infusion	AstraZeneca	09 Jun 2022
Colorectal cancer	-	Combination therapy, Inoperable/Unresectable, Metastatic disease	Phase II	Austria, France, Germany, Netherlands, Sweden, Switzerland	IV / Infusion	MedImmune	23 Nov 2018
Colorectal cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Canada	IV / Infusion	AstraZeneca, Canadian Cancer Trials Group	01 Aug 2016
Colorectal cancer	-	Late-stage disease, Metastatic disease	Phase II	USA	IV / Infusion	AstraZeneca, Memorial Sloan-Kettering Cancer Center, MedImmune	01 Oct 2014
Colorectal cancer	along with FOLFOX chemotherapy; followed by radiation treatment (either SCRT or LCRT)	Combination therapy, Late-stage disease, Neoadjuvant therapy	Phase II	United Kingdom	IV / Infusion	AstraZeneca, NHS Greater Glasgow and Clyde, Cancer Research UK	05 Oct 2020
Colorectal cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	MedImmune, University of Texas M. D. Anderson Cancer Center	02 Mar 2017
Colorectal cancer	In combination with Yttrium-90 radioembolization (Y90-RE); Liver-predominant metastatic colorectal cancer (mCRC), which is mismatch repair proficient/microsatellite stable (pMMR/MSS)	Metastatic disease	Phase I/II	USA	IV / Infusion	AstraZeneca, Biocompatibles International	07 Oct 2020
Colorectal cancer	in combination with oleclumab and FOLFOX + bevacuzimab	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Phase I/II	Australia, Canada, Spain, USA	IV / Infusion	MedImmune	13 Sep 2019
Colorectal cancer	-	Combination therapy, In adults, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	France	IV / Infusion	AstraZeneca, Centre Leon Berard	29 Aug 2017
Cutaneous T-cell lymphoma	-	Combination therapy, Monotherapy, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	National Cancer Institute (USA)	01 Feb 2017
Diffuse large B cell lymphoma	-	Combination therapy, First-line therapy, Late-stage disease	Phase II	Austria, Denmark, Estonia, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 Feb 2017
Diffuse large B cell lymphoma	-	Combination therapy, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	Pharmacyclics	28 May 2015
Diffuse large B cell lymphoma	-	Combination therapy, Second-line therapy or greater	No development reported (I)	France, Ireland, Italy, United Kingdom	IV / Infusion	AstraZeneca	28 Dec 2019
Diffuse large B cell lymphoma	-	Second-line therapy or greater	No development reported (I)	Australia	IV / Infusion	AstraZeneca	28 Aug 2022
Endometrial cancer	in combination with Olaparib	Combination therapy, First-line therapy, Late-stage disease, Recurrent	Phase III	Australia, Belgium, Brazil, Canada, China, Colombia, Estonia, Germany, Greece, Hong Kong, Hungary, India, Israel, Japan, Lithuania, Mexico, Poland, Russia, Singapore, South Korea, Spain, USA	IV / Infusion	AstraZeneca	21 May 2020
Endometrial cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Endometrial cancer	-	Late-stage disease, Recurrent, Second-line therapy or greater	Phase II	Australia	IV / Infusion	AstraZeneca, University of Sydney	15 Feb 2017
Endometrial cancer	-	Monotherapy, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	Memorial Sloan-Kettering Cancer Center	01 Jan 2017
Endometrial cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Recurrent	Phase II	Netherlands	IV / Infusion	AstraZeneca	08 Jul 2019
Endometrial cancer	-	Adjunctive treatment, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	07 Aug 2020
Endometrial cancer	with tremelimumab for treatment of cancer with microsatellite instability (MSI) and microsatellite stability (MSS)no	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	Spain	IV / Infusion	AstraZeneca	09 Jun 2022
Endometrial cancer	-	Combination therapy, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	Memorial Sloan-Kettering Cancer Center	01 Jan 2017
Fallopian tube cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Austria, Finland, Hungary, South Korea	IV / Infusion	AstraZeneca, Myriad Genetic Laboratories	04 Jan 2019
Fallopian tube cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Fallopian tube cancer	-	Combination therapy, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	18 May 2017
Fallopian tube cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy	Phase II	South Korea	IV / Infusion	AstraZeneca, Yonsei University College of Medicine	04 Jul 2019
Fallopian tube cancer	-	Chemotherapy-induced, First-line therapy, Neoadjuvant therapy	Phase I/II	France	IV / Infusion	AstraZeneca	18 Oct 2017
Fallopian tube cancer	-	Combination therapy, First-line therapy	Phase I/II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	01 Jul 2016
Gallbladder cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	Germany	IV / Infusion	AIO Studien gGmbH, AstraZeneca	02 May 2018
Gastric cancer	-	Adjuvant therapy, First-line therapy, Neoadjuvant therapy	Phase III	Argentina, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Hungary, Japan, Netherlands, Peru, Poland, Russia, South Korea, Spain, Taiwan, Turkey, USA, United Kingdom	IV / Infusion	AstraZeneca	17 Nov 2020
Gastric cancer	In combination with tremelimumab	Combination therapy, Late-stage disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	MedImmune	08 Sep 2016
Gastric cancer	In combination with olaparib and paclitaxel	Combination therapy, Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase II	South Korea	IV / Infusion	AstraZeneca	26 Nov 2018
Gastric cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater	Phase I/II	Canada, Singapore	IV / Infusion	MedImmune	01 Mar 2015
Gastric cancer	-	Combination therapy, Late-stage disease, Second-line therapy or greater	Phase I/II	Japan, Taiwan	IV / Infusion	MedImmune	01 Mar 2015
Gastric cancer	oesophagael or gastroesophageal junction adenocarcinoma	Combination therapy, First-line therapy	Phase I/II	USA	IV / Infusion	AstraZeneca, Memorial Sloan-Kettering Cancer Center	01 Nov 2016
Gastric cancer	-	Late-stage disease, Metastatic disease, Monotherapy, Recurrent, Second-line therapy or greater	Phase I/II	Canada, Japan, Singapore, South Korea, Taiwan, USA	IV / Infusion	MedImmune	01 Mar 2015
Gastrointestinal cancer	-	Combination therapy, Late-stage disease, Second-line therapy or greater	No development reported (I)	USA	IV / Infusion	AstraZeneca, University of Kansas Medical Center	28 Aug 2022
Germ cell cancer	-	Late-stage disease, Monotherapy, Second-line therapy or greater	Phase II	Italy	IV / Injection	AstraZeneca, Fondazione IRCCS Istituto Nazionale dei Tumori	01 Feb 2017
Germ cell cancer	-	Combination therapy, Late-stage disease, Second-line therapy or greater	Phase II	Italy	IV / Injection	AstraZeneca, Fondazione IRCCS Istituto Nazionale dei Tumori	01 Feb 2017
Germ cell cancer	-	Combination therapy, Second-line therapy or greater	Phase II	USA	IV / Injection	AstraZeneca	17 May 2017
Glioblastoma	-	Combination therapy, Late-stage disease, Recurrent	Phase II	USA	IV / Infusion	AstraZeneca, Northwestern University, National Cancer Institute (USA), MedImmune	01 Sep 2016
Glioblastoma	-	Late-stage disease, Monotherapy, Recurrent	Phase II	USA	IV / Infusion	AstraZeneca, National Cancer Institute (USA), MedImmune, GSK	01 Sep 2016
Glioblastoma	-	-	Phase II	Australia, USA	IV / Infusion	Ludwig Institute for Cancer Research, MedImmune	01 Feb 2015
Glioblastoma	-	Late-stage disease, Recurrent	Phase I/II	France	IV / Infusion	AstraZeneca, Institut Claudius Regaud	27 Mar 2017
HER2 negative breast cancer	-	Combination therapy, Neoadjuvant therapy	Phase II	France	IV / Infusion		15 Feb 2017
HER2 negative breast cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	Japan	IV / Infusion	AstraZeneca, Kyoto Breast Cancer Research Network	04 Jan 2017
Haematological malignancies	-	In adolescents, In children, In infants, In neonates, Late-stage disease, Monotherapy	Phase I/II	USA	IV / Infusion	AstraZeneca	07 Mar 2019
Haematological malignancies	in combination with tremelimumab	Combination therapy, In adolescents, In children, In infants, In neonates, Late-stage disease	Phase I/II	France, Italy, Netherlands, USA, United Kingdom	IV / Infusion	AstraZeneca	07 Mar 2019
Head and neck cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Japan, Philippines, Poland, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Thailand, USA, Ukraine, United Kingdom, Vietnam	IV / Infusion	AstraZeneca	01 Oct 2015
Head and neck cancer	PD-L1-positive/negative	Combination therapy, Second-line therapy or greater	Phase III	Australia, Chile, Hungary, Israel, Spain, Taiwan, USA	IV / Infusion	MedImmune	18 Sep 2015
Head and neck cancer	PD-L1-positive/negative	Combination therapy, Metastatic disease, Recurrent, Second-line therapy or greater	Phase III	Argentina, Belgium, Brazil, Bulgaria, Croatia, Czech Republic, France, Italy, Japan, Romania, Russia, Serbia, South Korea, Ukraine	IV / Infusion	AstraZeneca	10 Sep 2015
Head and neck cancer	PD-L1-positive/negative PD-L1-negative	Combination therapy, Second-line therapy or greater	Phase III	France, Poland	IV / Infusion	AstraZeneca	10 Sep 2015
Head and neck cancer	-	First-line therapy, Late-stage disease, Monotherapy	Phase III	Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Japan, Philippines, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Thailand, USA, Ukraine, United Kingdom, Vietnam	IV / Infusion	AstraZeneca	01 Oct 2015
Head and neck cancer	PD-L1-positive/negative	Combination therapy, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	Australia, Israel	IV / Infusion	AstraZeneca	01 Apr 2015
Head and neck cancer	-	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy	Phase II	USA	IV / Infusion	Celgene International SARL, UNC Lineberger Comprehensive Cancer Center	19 Dec 2017
Head and neck cancer	PD-L1 positive/ PD-L1 ngative	Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	Georgia	IV / Infusion	AstraZeneca	01 Apr 2015
Head and neck cancer	PD-L1 positive/ PD-L1 ngative	Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	Malaysia, South Korea, Taiwan	IV / Infusion	AstraZeneca, MedImmune	01 Apr 2015
Head and neck cancer	PD-L1-negative	Combination therapy, Second-line therapy or greater	Phase II	Belgium, Canada, Germany, United Kingdom	IV / Infusion	MedImmune	14 Sep 2015
Head and neck cancer	IN COMBINATION WITH OLAPARIB	Combination therapy, First-line therapy, In adults, In the elderly, Neoadjuvant therapy	Phase II	Greece	IV / Infusion	AstraZeneca	20 Oct 2016
Head and neck cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	MedImmune	30 Sep 2015
Head and neck cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable	Phase II	Germany	IV / Infusion	AstraZeneca, Charite - Universitatsmedizin Berlin	02 Aug 2018
Head and neck cancer	PD-L1 positive	Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	Belgium, Canada, Czech Republic, France, Germany, Hungary, Spain, USA (fast track), United Kingdom	IV / Infusion	MedImmune	10 Sep 2015
Head and neck cancer	IN COMBINATION WITH DURVALUMAB	First-line therapy, In adults, In the elderly, Monotherapy, Neoadjuvant therapy	Phase II	Greece	IV / Infusion	AstraZeneca	20 Oct 2016
Head and neck cancer	in combination with axalimogene filolisbac	Combination therapy, Recurrent, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	MedImmune, Undisclosed	01 Apr 2015
Head and neck cancer	-	Diagnosis, Metastatic disease, Recurrent	Phase I/II	Netherlands	IV / Infusion	AstraZeneca, Radboud University	15 Apr 2019
Head and neck cancer	in combination with tremelimumab	Combination therapy, First-line therapy, Metastatic disease, Recurrent, Second-line therapy or greater	No development reported (I)	Canada, USA	IV / Infusion	MedImmune	28 Aug 2022
Head and neck cancer	-	Adjuvant therapy, Combination therapy	No development reported (I)	USA	IV / Infusion	AstraZeneca	28 Aug 2022
Liver cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease	Registered	European Union, Japan, USA	IV / Infusion	AstraZeneca	02 Jun 2023
Liver cancer	-	First-line therapy, Inoperable/Unresectable, Late-stage disease, Monotherapy	Registered	Japan	IV / Infusion	AstraZeneca	28 Dec 2022
Liver cancer	-	First-line therapy, Inoperable/Unresectable, Late-stage disease, Monotherapy	Preregistration	European Union	IV / Infusion	AstraZeneca	12 Oct 2023
Liver cancer	-	Combination therapy, First-line therapy, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease	Phase III	South Korea	IV / Infusion	AstraZeneca	11 Oct 2017
Liver cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease	Phase III	Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Russia, Spain, Taiwan, Thailand, Ukraine, Vietnam	IV / Infusion	AstraZeneca	11 Oct 2017
Liver cancer	-	First-line therapy, Monotherapy	Phase III	South Korea	IV / Infusion	AstraZeneca	29 Apr 2019
Liver cancer	transarterial chemoembolization (TACE) treatment	Combination therapy, Monotherapy	Phase III	Australia, Brazil, Canada, China, France, Hong Kong, India, Italy, Japan, Mexico, South Korea, Spain, Taiwan, Thailand, USA, Vietnam	IV / Infusion	AstraZeneca	30 Nov 2018
Liver cancer	-	First-line therapy, Inoperable/Unresectable, Late-stage disease, Monotherapy	Phase III	Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Russia, South Korea, Spain, Taiwan, Thailand, USA, Ukraine, Vietnam	IV / Infusion	AstraZeneca	11 Oct 2017
Liver cancer	in patients with hepatitis B infections	Late-stage disease	Phase II	Taiwan	IV / Infusion	AstraZeneca	02 Nov 2020
Liver cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	USA	IV / Infusion	AstraZeneca	14 May 2018
Liver cancer	in combination with bevacizumab after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in patients with unresectable hepatocellular carcinoma amenable to embolization	Combination therapy, First-line therapy, Inoperable/Unresectable	Phase II	USA	IV / Infusion	AstraZeneca	13 Feb 2024
Liver cancer	in combination with tremelimumab	Combination therapy, Late-stage disease	Phase II	Ireland	IV / Infusion	AstraZeneca	28 May 2020
Liver cancer	-	Inoperable/Unresectable, Monotherapy	Phase II	Italy, Japan, Spain	IV / Infusion	MedImmune	01 Oct 2015
Liver cancer	-	Combination therapy, Inoperable/Unresectable, Monotherapy	Phase II	Hong Kong, Singapore, Taiwan, USA	IV / Infusion	MedImmune	01 Oct 2015
Liver cancer	-	Combination therapy, First-line therapy	Phase II	USA	IV / Infusion	AstraZeneca	04 Apr 2019
Liver cancer	-	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Phase I/II	Unknown	IV / Infusion	AstraZeneca, AVEO Oncology	31 Aug 2019
Liver cancer	Neoadjuvant treatment with tremelimumab and durvalumab with or without Selective Internal Yttrium-90 Radioembolization (SIRT) in participants with resectable hepatocellular carcinoma	Neoadjuvant therapy	Phase I	USA	IV / Infusion	AstraZeneca, Dana-Farber Cancer Institute	21 Apr 2023
Liver cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	France, USA	IV / Infusion	Innate Pharma, MedImmune	28 Aug 2022
Liver cancer	-	Combination therapy, Late-stage disease	No development reported (I)	USA	IV / Infusion	National Cancer Institute (USA), University of Southern California	28 Aug 2022
Lung cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase I/II	France	IV / unspecified	Gustave Roussy	20 Jun 2017
Lymphoma	-	Monotherapy, Second-line therapy or greater	Phase I/II	France	IV / Infusion	Celgene International SARL	11 May 2016
Lymphoma	-	Combination therapy, Second-line therapy or greater	Phase I/II	France, Germany, Italy, Japan, Netherlands, USA, United Kingdom	IV / Infusion	Celgene Corporation	11 May 2016
Lymphoma	-	Monotherapy, Second-line therapy or greater	Phase I/II	Germany, Italy, Japan, Netherlands, USA, United Kingdom	IV / Infusion	Celgene Corporation	11 May 2016
Lymphoma	-	In adolescents, In children, In infants, Second-line therapy or greater, Treatment-resistant	No development reported (I)	USA	IV / Infusion	Childrens Hospital Los Angeles	28 Dec 2019
Lymphoproliferative disorders	solitary bone plasmacytoma	-	No development reported (I)	USA	IV / unspecified	Celgene International SARL, Memorial Sloan-Kettering Cancer Center	28 Aug 2020
Malignant melanoma	in combination with ceralasertib; in case of primary or secondary resistance to PD-(L)1 inhibition	Combination therapy, Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase II	Germany, Italy, Spain	IV / Infusion	AstraZeneca	08 Mar 2022
Malignant melanoma	in combination with IMC gp100 and tremelimumab	Combination therapy, Inoperable/Unresectable, Late-stage disease	Phase I/II	United Kingdom	IV / Infusion	Immunocore, MedImmune	20 Jan 2016
Malignant melanoma	in combination with IMC gp100 and tremelimumab	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	Immunocore, MedImmune	30 Nov 2015
Malignant melanoma	-	Combination therapy	Phase I/II	Canada, France, USA	IV / Infusion	GSK, MedImmune	01 Nov 2013
Malignant-mesothelioma	In combination with pemetrexed and cisplastin	Combination therapy, First-line therapy, Inoperable/Unresectable	Phase III	Australia	IV / Infusion	AstraZeneca	01 Feb 2021
Malignant-mesothelioma	-	Combination therapy	Phase II	USA	IV / Infusion	AstraZeneca	10 Apr 2017
Malignant-mesothelioma	-	Combination therapy, First-line therapy, Inoperable/Unresectable	Phase II	USA	IV / Infusion	AstraZeneca	01 May 2017
Malignant-mesothelioma	-	Combination therapy, Inoperable/Unresectable	Phase II	Italy	IV / Infusion	MedImmune	01 Oct 2015
Multiple myeloma	in combination with daratumumab	Combination therapy, Second-line therapy or greater	Phase II	Austria, Belgium, Canada, Denmark, Germany, Greece, Italy, Netherlands, Spain, Sweden, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 Feb 2017
Multiple myeloma	-	Combination therapy, Newly diagnosed	Suspended (I)	Canada, Denmark, Finland, Germany, Italy, Netherlands, Spain, USA	IV / Infusion	Celgene International SARL	07 Sep 2017
Multiple myeloma	-	Monotherapy, Second-line therapy or greater	No development reported (I)	Canada, France, Germany, Italy, Netherlands, Spain, USA	IV / Infusion	Celgene International SARL	28 Dec 2019
Multiple myeloma	in combination with pomalidomide	Combination therapy, Second-line therapy or greater	No development reported (I)	France	IV / Infusion	Celgene International SARL	28 Dec 2019
Myelodysplastic syndromes	in combination with azacitidine	Combination therapy, Second-line therapy or greater	Phase II	Australia, Belgium, France, Germany, Poland, Spain, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 Jul 2015
Myelodysplastic syndromes	in combination with azacitidine	Combination therapy, First-line therapy	Phase II	Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Portugal, Spain, USA, United Kingdom	IV / Infusion	Celgene International SARL	01 Jun 2016
Myelodysplastic syndromes	-	Monotherapy, Second-line therapy or greater	No development reported (I)	France, Germany, USA, United Kingdom	IV / Infusion	MedImmune	28 Dec 2019
Neuroendocrine tumours	Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Spain	IV / Infusion	Grupo Espanol de Tumores Neuroendocrinos	02 Mar 2017
Non-Hodgkin's lymphoma	-	Monotherapy	Phase II	USA	IV / unspecified	AstraZeneca	04 Apr 2021
Non-Hodgkin's lymphoma	-	Combination therapy	Phase II	USA	IV / unspecified	AstraZeneca	04 Apr 2021
Non-Hodgkin's lymphoma	-	Combination therapy, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	Celgene International SARL, Juno Therapeutics	30 Oct 2017
Non-Hodgkin's lymphoma	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	USA	IV / unspecified	Juno Therapeutics, MedImmune	28 Dec 2019
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Marketed	Japan	IV / Infusion	AstraZeneca	29 Dec 2022
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Marketed	Japan, Netherlands	IV / Infusion	MedImmune	24 Aug 2022
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Marketed	USA	IV / Infusion	AstraZeneca, MedImmune	31 Dec 2018
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Registered	USA	IV / Infusion	AstraZeneca	11 Nov 2022
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Registered	Brazil, China	IV / Infusion	AstraZeneca	12 Dec 2019
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Registered	European Union, India, Switzerland	IV / Infusion	AstraZeneca, MedImmune	24 Sep 2018
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease	Registered	European Union	IV / Infusion	AstraZeneca	22 Feb 2023
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Registered	Canada	IV / Infusion	MedImmune	09 May 2018
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Preregistration	South Korea	IV / Infusion	MedImmune	31 Dec 2017
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Canada, South Korea, Taiwan	IV / Infusion	MedImmune	18 Aug 2015
Non-small cell lung cancer	-	Combination therapy, First-line therapy, In adults, In the elderly, Late-stage disease, Metastatic disease	Phase III	Brazil, Bulgaria, China, Hong Kong, Hungary, Mexico, Peru, Poland, Russia, South Africa, South Korea, Taiwan, Thailand, USA, Ukraine, Vietnam	IV / Infusion	AstraZeneca	01 Jun 2017
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase III	Australia, Chile, Mexico, Peru, Singapore, South Africa, Taiwan, Thailand, Turkey, Vietnam	IV / Infusion	MedImmune	01 May 2014
Non-small cell lung cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase III	Australia, Chile, Greece, Hong Kong, Israel, Serbia, Thailand	IV / Infusion	AstraZeneca	13 Jan 2015
Non-small cell lung cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease	Phase III	USA	IV / Infusion	AstraZeneca	07 Feb 2022
Non-small cell lung cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase III	Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Romania, Russia, Singapore, South Korea, Spain, Taiwan, USA, United Kingdom	IV / Infusion	MedImmune	30 Sep 2015
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russia, Saudi Arabia, Singapore, Spain, Sweden, Switzerland, Thailand, Turkey, USA, Ukraine, United Kingdom, Vietnam	IV / Infusion	AstraZeneca	01 Nov 2015
Non-small cell lung cancer	-	Adjuvant therapy	Phase III	Australia, Brazil, Canada, China, France, Italy, Japan, New Zealand, Poland, Romania, South Korea, Ukraine	IV / Infusion	Canadian Cancer Trials Group	22 Oct 2019
Non-small cell lung cancer	-	First-line therapy, Late-stage disease, Monotherapy	Phase III	Canada, South Korea, Taiwan	IV / Infusion	MedImmune	18 Aug 2015
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase III	Israel	IV / Infusion	AstraZeneca	01 May 2014
Non-small cell lung cancer	-	Combination therapy, Late-stage disease, Second-line therapy or greater	Phase III	Canada, South Korea	IV / Infusion	MedImmune	01 Aug 2015
Non-small cell lung cancer	-	Inoperable/Unresectable	Phase III	Puerto Rico	IV / unspecified	AstraZeneca	06 Mar 2019
Non-small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Phase III	Germany, United Kingdom	IV / Infusion	AstraZeneca	01 Jun 2017
Non-small cell lung cancer	-	Adjuvant therapy, In adults, In the elderly	Phase III	Bulgaria, Hungary, Netherlands, Singapore, Spain, Taiwan, USA	IV / Infusion	Canadian Cancer Trials Group	22 Oct 2019
Non-small cell lung cancer	with domvanalimab In combination with domvanalimab	Combination therapy, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase III	Hungary, Taiwan, Turkey, USA	IV / Infusion	AstraZeneca	28 Apr 2022
Non-small cell lung cancer	-	First-line therapy, Late-stage disease, Monotherapy	Phase III	Australia, Belgium, France, Germany, Hungary, Italy, Japan, Netherlands, Russia, Spain, Switzerland, Thailand, USA, Vietnam	IV / Infusion	AstraZeneca	01 Jul 2015
Non-small cell lung cancer	-	First-line therapy, Late-stage disease, Metastatic disease, Monotherapy	Phase III	China, Russia, South Korea, Thailand, Vietnam	IV / Infusion	AstraZeneca	01 Jan 2017
Non-small cell lung cancer	In combination with tremelimumab	Combination therapy, Early-stage disease, Neoadjuvant therapy	Phase II/III	Netherlands	IV / Infusion	AstraZeneca	18 May 2021
Non-small cell lung cancer	-	Late-stage disease, Second-line therapy or greater	Phase II/III	USA	IV / Infusion	AstraZeneca, MedImmune	14 Jun 2014
Non-small cell lung cancer	-	Early-stage disease, In adults, In the elderly, Neoadjuvant therapy	Phase II	France	IV / Infusion		22 Sep 2016
Non-small cell lung cancer	Resectable non-small cell lung cancerin combination with chemotherapy and Oleclumab or Monalizumab	Adjuvant therapy, Combination therapy, Early-stage disease, First-line therapy	Phase II	Canada, France, Italy, Portugal, South Korea, Spain, USA	IV / Infusion	AstraZeneca	20 Dec 2021
Non-small cell lung cancer	-	Combination therapy, In adolescents, In adults, In children, In the elderly, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	China	IV / Infusion	AstraZeneca	23 Nov 2022
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase II	Russia, United Kingdom	IV / Infusion	AstraZeneca	26 Nov 2020
Non-small cell lung cancer	-	In the elderly, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Germany	IV / Infusion	AIO Studien gGmbH, Celgene International SARL, AstraZeneca	14 Dec 2017
Non-small cell lung cancer	in combination with chemotherapy and Oleclumab or MonalizumabResectable non-small cell lung cancer Resectable non-small cell lung cancerin combination with chemotherapy and Oleclumab or Monalizumab	Combination therapy, Early-stage disease, First-line therapy, Neoadjuvant therapy	Phase II	Canada, France, Italy, Portugal, South Korea, Spain, USA	IV / Infusion	AstraZeneca	20 Dec 2021
Non-small cell lung cancer	-	Combination therapy, Neoadjuvant therapy	Phase II	Canada, France, Italy, Portugal, Spain, Switzerland, USA	IV / Infusion	MedImmune	06 Jun 2019
Non-small cell lung cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy	Phase II	Spain, Switzerland	IV / Infusion	AstraZeneca	19 Nov 2019
Non-small cell lung cancer	-	Late-stage disease, Neoadjuvant therapy	Phase II	Switzerland	IV / Infusion	Swiss Group for Clinical Cancer Research	01 Mar 2016
Non-small cell lung cancer	durvalumab in combination with monalizumab/ oleclumabno durvalumab in combination with oleclumab/monalizumab durvalumab in combination with monalizumab/ oleclumab	Combination therapy, Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater	Phase II	Canada, France, Hong Kong, Italy, Poland, Portugal, Spain, Taiwan, USA	IV / Infusion	MedImmune	19 Dec 2018
Non-small cell lung cancer	-	Adjuvant therapy, Late-stage disease	Phase II	USA	IV / Infusion	AstraZeneca	15 Jul 2021
Non-small cell lung cancer	-	Inoperable/Unresectable, Second-line therapy or greater	Phase II	France	IV / Infusion	AstraZeneca	16 Apr 2019
Non-small cell lung cancer	-	Late-stage disease, Second-line therapy or greater	Phase II	Austria, Czech Republic, Philippines, Thailand	IV / Infusion	MedImmune	01 Feb 2014
Non-small cell lung cancer	-	Monotherapy, Neoadjuvant therapy	Phase II	Canada, France, Italy, Portugal, Spain, Switzerland, USA	IV / Infusion	MedImmune	08 Mar 2019
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease, Monotherapy, Second-line therapy or greater	Phase II	Canada, France, Hong Kong, Italy, Poland, Portugal, Spain, Taiwan, USA	IV / Infusion	MedImmune	19 Dec 2018
Non-small cell lung cancer	-	In adults, In the elderly, Inoperable/Unresectable, Late-stage disease, Neoadjuvant therapy	Phase II	Netherlands	IV / Infusion	AstraZeneca, Radboud University	23 Sep 2019
Non-small cell lung cancer	-	Combination therapy, Late-stage disease, Metastatic disease	Phase II	Canada	IV / Infusion	AstraZeneca, National Health and Medical Research Council, Fondazione IRCCS Istituto Nazionale dei Tumori, Canadian Cancer Trials Group	15 Feb 2017
Non-small cell lung cancer	-	Adjuvant therapy, Late-stage disease	Phase II	Switzerland	IV / Infusion	Swiss Group for Clinical Cancer Research	01 Mar 2016
Non-small cell lung cancer	-	Early-stage disease, First-line therapy	Phase II	USA	IV / Infusion	AstraZeneca	01 Nov 2016
Non-small cell lung cancer	-	First-line therapy, In the elderly, Late-stage disease, Metastatic disease	Phase II	Germany	IV / Infusion	AIO Studien gGmbH, Celgene International SARL, AstraZeneca	14 Dec 2017
Non-small cell lung cancer	-	Combination therapy, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease, Metastatic disease	Phase II	Hungary	IV / Infusion	AstraZeneca	21 Dec 2018
Non-small cell lung cancer	-	First-line therapy, In adults, In the elderly, Neoadjuvant therapy	Phase II	Austria, Canada, Czech Republic, France, Germany, Hungary, Italy, Portugal, Spain, Sweden, USA	IV / Infusion	AstraZeneca	22 Feb 2024
Non-small cell lung cancer	with radiation therapy	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease	Phase II	Japan	IV / Infusion	AstraZeneca	04 Oct 2019
Non-small cell lung cancer	-	In adults, In the elderly, Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	Phase II	Hungary, USA	IV / Infusion	AstraZeneca	21 Dec 2018
Non-small cell lung cancer	-	Inoperable/Unresectable	Phase II	Germany, Italy, Spain, USA, United Kingdom	IV / Infusion	AstraZeneca	16 Apr 2019
Non-small cell lung cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	Belgium, Canada, Russia, South Korea, Spain, Taiwan, USA	IV / Infusion	AstraZeneca	03 Jan 2023
Non-small cell lung cancer	-	Combination therapy, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	MedImmune, Mirati Therapeutics	01 May 2016
Non-small cell lung cancer	-	Inoperable/Unresectable, Late-stage disease	Phase I/II	USA	SC / Injection	AstraZeneca	28 Jun 2021
Non-small cell lung cancer	-	First-line therapy, Late-stage disease, Metastatic disease, Monotherapy	Discontinued (III)	Australia	IV / Infusion	AstraZeneca	28 Feb 2023
Oesophageal cancer	-	Combination therapy, In adults, In the elderly, Inoperable/Unresectable, Late-stage disease	Phase III	South Korea, Taiwan	IV / Infusion	AstraZeneca	19 Oct 2020
Oesophageal cancer	-	Adjuvant therapy, First-line therapy, Neoadjuvant therapy	Phase III	Argentina, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Hungary, Japan, Netherlands, Peru, Poland, Russia, South Korea, Spain, Taiwan, Turkey, USA, United Kingdom	IV / Infusion	AstraZeneca	17 Nov 2020
Oesophageal cancer	-	Late-stage disease, Metastatic disease, Monotherapy, Recurrent, Second-line therapy or greater	Phase II	Canada, Japan, Singapore, South Korea, Taiwan	IV / Infusion	AstraZeneca	31 Mar 2015
Oesophageal cancer	-	Late-stage disease, Second-line therapy or greater	Phase II	United Kingdom	IV / Infusion	AstraZeneca	30 Oct 2018
Oesophageal cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	Canada, Japan, Singapore, South Korea, Taiwan, USA	IV / Infusion	AstraZeneca	31 Mar 2015
Oesophageal cancer	-	Late-stage disease, Metastatic disease, Monotherapy, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, MedImmune, Big Ten Cancer Research Consortium	27 Apr 2016
Oesophageal cancer	-	Adjuvant therapy	Phase II	South Korea	IV / Infusion	Samsung Medical Center	01 Feb 2016
Oesophageal cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase I/II	France	IV / Infusion	Gustave Roussy	20 Jun 2017
Oesophageal cancer	-	Late-stage disease, Neoadjuvant therapy, Second-line therapy or greater	Phase I/II	United Kingdom	IV / Infusion	AstraZeneca, Ludwig Institute for Cancer Research	01 Jun 2016
Oropharyngeal cancer	-	Combination therapy, Late-stage disease	Phase II	Canada	IV / unspecified	AstraZeneca, Centre hospitalier de l'Universite de Montreal	31 Jan 2018
Oropharyngeal cancer	-	First-line therapy, Newly diagnosed	Phase II	France	IV / unspecified	AstraZeneca, Institut Claudius Regaud	01 Mar 2019
Oropharyngeal cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	USA	IV / unspecified	AstraZeneca, M. D. Anderson Cancer Center	28 Aug 2020
Oropharyngeal cancer	-	Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	No development reported (I)	USA	IV / unspecified	AstraZeneca, M. D. Anderson Cancer Center	28 Aug 2020
Ovarian cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Austria, Finland, Hungary, South Korea	IV / Infusion	AstraZeneca, Myriad Genetic Laboratories	04 Jan 2019
Ovarian cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Ovarian cancer	-	Adjunctive treatment, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	02 Aug 2020
Ovarian cancer	-	Combination therapy, Recurrent, Second-line therapy or greater	Phase II	Denmark	IV / Infusion	AstraZeneca, Nordic Society of Gynaecological - Clinical Trial Unit, European Network of Gynaecological Oncological Trial Groups	15 Dec 2021
Ovarian cancer	-	Combination therapy, Metastatic disease, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	18 May 2017
Ovarian cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy	Phase II	South Korea	IV / Infusion	AstraZeneca, Yonsei University College of Medicine	04 Jul 2019
Ovarian cancer	-	Combination therapy, First-line therapy	Phase I/II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	01 Jul 2016
Ovarian cancer	-	Combination therapy, First-line therapy, Neoadjuvant therapy	Phase I/II	France	IV / Infusion	AstraZeneca	18 Oct 2017
Ovarian cancer	-	Combination therapy, Recurrent, Second-line therapy or greater	Phase I/II	Switzerland	IV / Infusion	Ludwig Institute for Cancer Research, VentiRx Pharmaceuticals, MedImmune	01 Nov 2015
Ovarian cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	France	IV / Infusion	AstraZeneca	28 Aug 2022
Pancreatic cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II/III	USA	IV / Infusion	AstraZeneca	01 Oct 2015
Pancreatic cancer	gemcitabine, nab-paclitaxel, and oleclumab	Adjuvant therapy, Combination therapy, Early-stage disease, First-line therapy, Neoadjuvant therapy	Phase II	USA	IV / Infusion	M. D. Anderson Cancer Center	28 Sep 2021
Pancreatic cancer	In combination with chemoradiotherapy (CCRT/gemcitabine)	Adjuvant therapy, Combination therapy, First-line therapy, Neoadjuvant therapy	Phase II	South Korea	IV / Infusion	AstraZeneca	29 Nov 2018
Pancreatic cancer	in combination with tremelimumab	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Neoadjuvant therapy	Phase II	Belgium	IV / Infusion	AstraZeneca	04 May 2020
Pancreatic cancer	-	Combination therapy, Metastatic disease	Phase II	United Kingdom	IV / Infusion	AstraZeneca	25 Mar 2016
Pancreatic cancer	-	Combination therapy, First-line therapy, Metastatic disease	Phase II	Canada	IV / Infusion	AstraZeneca, Canadian Cancer Trials Group	01 Aug 2016
Pancreatic cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	Canada, Germany, Netherlands, South Korea	IV / Infusion	AstraZeneca	01 Nov 2015
Pancreatic cancer	-	Adjuvant therapy, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, University of Colorado at Denver	12 Jun 2017
Pancreatic cancer	-	Metastatic disease, Monotherapy, Second-line therapy or greater	Phase II	Canada, Germany, Netherlands, South Korea, USA	IV / Infusion	AstraZeneca	01 Nov 2015
Pancreatic cancer	in combination with oleclumab	Combination therapy, In adults, In the elderly, Metastatic disease, Second-line therapy or greater	Phase I/II	Australia, Norway, Spain, USA	IV / Infusion	MedImmune	21 Jun 2018
Pancreatic cancer	in combination with oleclumab	Combination therapy, First-line therapy, In adults, In the elderly, Metastatic disease	Phase I/II	Australia, Norway, Spain, USA	IV / Infusion	MedImmune	21 Jun 2018
Pancreatic cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	France	IV / Infusion	AstraZeneca, Centre Leon Berard	28 Dec 2019
Pancreatic cancer	-	Combination therapy, Metastatic disease, Recurrent, Second-line therapy or greater	No development reported (I)	France, USA	IV / Infusion	AstraZeneca, Eli Lilly and Company	28 Dec 2019
Pancreatic cancer	-	Combination therapy, Late-stage disease	No development reported (I)	USA	IV / Infusion	National Cancer Institute (USA), University of Southern California	28 Aug 2022
Pancreatic cancer	-	Combination therapy, Metastatic disease, Recurrent, Second-line therapy or greater	No development reported (I)	South Korea, Spain	IV / Infusion	AstraZeneca	28 Dec 2019
Pancreatic cancer	-	Combination therapy, Inoperable/Unresectable, Late-stage disease	Discontinued (I)	USA	IV / Infusion	AstraZeneca	04 Mar 2019
Pancreatic cancer	-	Inoperable/Unresectable, Late-stage disease, Monotherapy	Discontinued (I)	USA	IV / Infusion	AstraZeneca	04 Mar 2019
Peripheral T-cell lymphoma	-	Combination therapy, Monotherapy, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	National Cancer Institute (USA)	01 Feb 2017
Peritoneal cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Austria, Finland, Hungary, South Korea	IV / Infusion	AstraZeneca, Myriad Genetic Laboratories	04 Jan 2019
Peritoneal cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy	Phase II	South Korea	IV / Infusion	AstraZeneca, Yonsei University College of Medicine	04 Jul 2019
Peritoneal cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Peritoneal cancer	-	Combination therapy, Recurrent, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	18 May 2017
Peritoneal cancer	-	Combination therapy, First-line therapy	Phase I/II	USA	IV / Infusion	AstraZeneca, University of Texas M. D. Anderson Cancer Center	01 Jul 2016
Peritoneal cancer	-	Combination therapy, First-line therapy, Neoadjuvant therapy	Phase I/II	France	IV / Infusion	AstraZeneca	18 Oct 2017
Prostate cancer	-	Combination therapy, Hormone refractory, Metastatic disease	Phase II	Canada	IV / Infusion	AstraZeneca	01 May 2016
Prostate cancer	In combination with AZD 4635 and oleclumab in castration-resistant prostrate cancer	Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	29 Aug 2019
Prostate cancer	in combination with durvalumab and oleclumab in castration-resistant prostate cancer	Combination therapy, Hormone refractory, In adults, In the elderly, Metastatic disease, Second-line therapy or greater	Phase II	Belgium, Denmark, France, Germany, Italy, Netherlands, South Korea, Spain, USA	IV / Infusion	AstraZeneca	20 Oct 2020
Prostate cancer	-	Combination therapy, First-line therapy, Hormone refractory, Metastatic disease	Phase II	USA	IV / Infusion	M. D. Anderson Cancer Center, MedImmune	14 Jul 2017
Prostate cancer	Prostate cancer patients with oligometastatic relapse	Combination therapy, Metastatic disease	Phase II	France	IV / Infusion	AstraZeneca	21 Mar 2019
Prostate cancer	-	Hormone refractory, Metastatic disease, Monotherapy	Phase II	Canada	IV / Infusion	AstraZeneca	01 May 2016
Renal cancer	in combination with guadecitabine	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	USA	IV / unspecified	AstraZeneca, Big Ten Cancer Research Consortium	19 Dec 2017
Renal cell carcinoma	-	Adjuvant therapy, Combination therapy	Phase III	United Kingdom	IV / Infusion	AstraZeneca, University College London	22 Nov 2017
Renal cell carcinoma	-	Adjuvant therapy, Monotherapy	Phase III	United Kingdom	IV / Infusion	AstraZeneca, University College London	22 Nov 2017
Renal cell carcinoma	in combination with guadecitabine	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	AstraZeneca, Big Ten Cancer Research Consortium	19 Dec 2017
Renal cell carcinoma	-	Late-stage disease, Neoadjuvant therapy	No development reported (I)	USA	IV / Infusion	Case Comprehensive Cancer Center	28 Jan 2020
Renal cell carcinoma	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (Clinical)	France, Spain	IV / Infusion	AstraZeneca	28 Dec 2019
Renal cell carcinoma	-	Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	No development reported (Clinical)	France, Spain	IV / Infusion	AstraZeneca	28 Dec 2019
Sarcoma	In combination with tremelimumab	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	M. D. Anderson Cancer Center, MedImmune	01 Aug 2016
Small cell lung cancer	for adult patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with standard-of-care (SoC) chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide) in combination with tremelimumab	Combination therapy, First-line therapy	Marketed	Netherlands, USA	IV / Infusion	AstraZeneca	24 Aug 2022
Small cell lung cancer	-	Combination therapy, First-line therapy	Registered	China, European Union, Japan, Singapore	IV / Infusion	AstraZeneca	19 Jul 2021
Small cell lung cancer	-	Combination therapy, Early-stage disease, Mid-stage disease, Second-line therapy or greater	Preregistration	China	IV / Infusion	AstraZeneca	01 Nov 2020
Small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase III	Bulgaria, Czech Republic, Germany, Italy	IV / Infusion	AstraZeneca	11 Nov 2021
Small cell lung cancer	in combination with Tremelimumab in combination with tremelimumab	Combination therapy, First-line therapy	Phase III	Argentina, Brazil, Czech Republic, Israel, Russia, South Korea, Taiwan, Turkey, Ukraine	IV / Infusion	AstraZeneca	27 Mar 2017
Small cell lung cancer	-	Combination therapy, First-line therapy, In adults, In the elderly, Late-stage disease	Phase III	China	IV / Infusion	AstraZeneca	07 Dec 2020
Small cell lung cancer	-	Combination therapy, Early-stage disease, Mid-stage disease, Second-line therapy or greater	Phase III	Argentina, Belgium, Canada, Czech Republic, Germany, India, Italy, Japan, Netherlands, Russia, South Korea, Spain, Taiwan, Turkey, USA, Vietnam	IV / Infusion	AstraZeneca	27 Sep 2018
Small cell lung cancer	Plus Chemotherapy	Combination therapy, First-line therapy, Metastatic disease	Phase III	Spain	IV / Infusion		16 Dec 2020
Small cell lung cancer	-	Early-stage disease, Mid-stage disease, Monotherapy, Second-line therapy or greater	Phase III	Russia	IV / Infusion	AstraZeneca	27 Sep 2018
Small cell lung cancer	-	Combination therapy, Metastatic disease, Second-line therapy or greater	Phase II	Germany, Hungary, Poland, Spain, Ukraine	IV / Infusion	AstraZeneca	24 Apr 2017
Small cell lung cancer	-	-	Phase II	France	IV / Infusion	UNICANCER	18 Jan 2023
Small cell lung cancer	-	Combination therapy, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	01 Apr 2016
Small cell lung cancer	-	Combination therapy, First-line therapy, Late-stage disease	Phase II	South Korea, USA	IV / Infusion	AstraZeneca	23 Feb 2021
Small cell lung cancer	in combination with monalizumab in combination with etoposide + carboplatin	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Phase II	Australia, USA	IV / Infusion	AstraZeneca	30 Jun 2023
Small cell lung cancer	in combination with AZD 6738	Combination therapy, Second-line therapy or greater	Phase II	South Korea	IV / Infusion	AstraZeneca, Samsung Medical Center	17 Jun 2020
Small cell lung cancer	in combination with amrubicin	Combination therapy, Recurrent	Phase II	Japan	IV / Infusion	AstraZeneca	11 Oct 2022
Small cell lung cancer	-	Late-stage disease	Phase I/II	USA	SC / Injection	AstraZeneca	28 Jun 2021
Soft tissue sarcoma	-	Combination therapy, First-line therapy, Late-stage disease, Metastatic disease	Phase II	Germany	IV / Infusion	AstraZeneca	15 Dec 2017
Soft tissue sarcoma	-	Combination therapy, Locally recurrent, Neoadjuvant therapy	Phase I/II	USA	IV / Infusion	AstraZeneca	21 Jun 2017
Soft tissue sarcoma	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	France	IV / Infusion	AstraZeneca, University of Maryland Greenbaum Cancer Center	28 Aug 2022
Solid tumours	in combination with tremelimumab	Combination therapy, In adults, In the elderly, Late-stage disease	Phase III	Canada, France, Germany, Italy, Netherlands, South Korea, USA, United Kingdom	IV / Infusion	AstraZeneca	05 Jun 2017
Solid tumours	-	Late-stage disease, Monotherapy	Phase III	Canada, South Korea, USA	IV / Infusion	AstraZeneca	17 Apr 2017
Solid tumours	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Belgium, Germany, Italy, Spain, USA	IV / Infusion	AstraZeneca, MedImmune	16 Dec 2016
Solid tumours	in combination with tremelimumab	Combination therapy, Second-line therapy or greater	Phase II	Canada	IV / Infusion	AstraZeneca, Canadian Cancer Trials Group	01 Aug 2016
Solid tumours	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	Netherlands, United Kingdom	IV / Infusion	AstraZeneca	25 Jan 2016
Solid tumours	-	Late-stage disease, Monotherapy	Phase II	Belgium, Netherlands, Poland	IV / Infusion	AstraZeneca	02 Nov 2015
Solid tumours	combination with olaparib	Combination therapy	Phase II	Canada	IV / unspecified	AstraZeneca, University Health Network	31 Dec 2019
Solid tumours	in combination with tremelimumab	Combination therapy, Late-stage disease	Phase II	Belgium, Netherlands, Poland	IV / Infusion	AstraZeneca	02 Nov 2015
Solid tumours	solid malignancies (phase I), nasopharyngeal carcinoma (phase II)	Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	Phase I/II	China	IV / Infusion	AstraZeneca	01 Dec 2016
Solid tumours	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	France	IV / Infusion	AstraZeneca, UNICANCER	20 Jun 2018
Solid tumours	in combination with tremelimumab	Combination therapy, In adolescents, In children, In infants, In neonates, Late-stage disease	Phase I/II	France, Italy, Netherlands, USA, United Kingdom	IV / Infusion	AstraZeneca	07 Mar 2019
Solid tumours	in combination with axalimogene filolisbac	Late-stage disease, Recurrent, Second-line therapy or greater	Phase I/II	USA	IV / Infusion	MedImmune, Undisclosed	01 Apr 2015
Solid tumours	-	In adolescents, In children, In infants, In neonates, Late-stage disease, Monotherapy	Phase I/II	USA	IV / Infusion	AstraZeneca	07 Mar 2019
Solid tumours	with monalizumab	Combination therapy, Late-stage disease, Metastatic disease, Recurrent	Phase I/II	Australia, Belgium, Canada, France, Hungary, Italy, New Zealand, South Korea, Spain, USA, United Kingdom	IV / Infusion	AstraZeneca	22 Feb 2016
Solid tumours	solid malignancies (phase I), nasopharyngeal carcinoma (phase II)	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase I/II	China	IV / Infusion	AstraZeneca	01 Dec 2016
Solid tumours	-	Combination therapy, Late-stage disease, Metastatic disease	Phase I	USA	IV / Infusion	AstraZeneca	02 Dec 2020
Solid tumours	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease	No development reported (I)	South Korea	IV / Infusion	AstraZeneca	28 Dec 2019
Solid tumours	in combination with tremelimumab	Combination therapy, Late-stage disease	No development reported (I)	Israel, Japan, Spain	IV / Infusion	MedImmune	28 Aug 2022
Solid tumours	-	Adjuvant therapy, Monotherapy	No development reported (I)	Canada	IV / Infusion	MedImmune	28 Dec 2019
Solid tumours	-	Combination therapy, Late-stage disease, Second-line therapy or greater	No development reported (I)	USA	IV / Infusion	AstraZeneca, Eli Lilly and Company	28 Dec 2019
Solid tumours	-	Combination therapy, Late-stage disease, Second-line therapy or greater	No development reported (I)	Australia	IV / Infusion	MedImmune	28 Aug 2022
Solid tumours	-	Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater	No development reported (I)	Israel, South Korea, Taiwan, USA	IV / Infusion	AstraZeneca, Eli Lilly and Company	28 Dec 2019
Solid tumours	-	In adolescents, In children, In infants, Second-line therapy or greater, Treatment-resistant	No development reported (I)	USA	IV / Infusion	Childrens Hospital Los Angeles	28 Dec 2019
Solid tumours	-	In adults, In the elderly, Late-stage disease	No development reported (I)	Japan	IV / Infusion	MedImmune	28 Aug 2022
Solid tumours	in combination with tremelimumab and chemoradiotherapy	Combination therapy, Late-stage disease	No development reported (I)	Taiwan	IV / Infusion	AstraZeneca	28 Aug 2022
Solid tumours	in combination with oleclumab	Combination therapy, In adults, In the elderly, Late-stage disease	No development reported (I)	Australia	IV / Infusion	MedImmune	28 Aug 2022
Solid tumours	-	In adults, In the elderly, Late-stage disease	No development reported (I)	South Korea, Taiwan	IV / Infusion	AstraZeneca	28 Aug 2022
Squamous cell cancer	In combination with tremelimumab	Combination therapy, In adolescents, In adults, In children, In the elderly, Late-stage disease, Second-line therapy or greater	Phase II	USA	IV / unspecified	National Cancer Institute (USA), SWOG	02 Oct 2017
Thyroid cancer	-	Combination therapy, First-line therapy, Metastatic disease	No development reported (I)	USA	IV / Infusion	AstraZeneca, Memorial Sloan-Kettering Cancer Center	28 May 2020
Triple negative breast cancer	in patients with stage I-III TNBC	Combination therapy, In adults, In the elderly, Second-line therapy or greater	Phase III	United Kingdom	IV / Infusion	AstraZeneca, Daiichi Sankyo Company	30 Nov 2022
Urogenital cancer	-	Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	Registered	Canada	IV / Infusion	AstraZeneca	06 Nov 2017
Urogenital cancer	urothelial cancer	Late-stage disease, Monotherapy, Second-line therapy or greater	Registered	Australia, Hong Kong, India, Israel, United Arab Emirates	IV / Infusion	AstraZeneca	16 Nov 2018
Urogenital cancer	-	Late-stage disease, Metastatic disease, Second-line therapy or greater	Registered	Brazil, Macau, Qatar	IV / Infusion	AstraZeneca	02 Jun 2019
Urogenital cancer	in combination with tremelimumab	Combination therapy, Inoperable/Unresectable, Metastatic disease, Second-line therapy or greater	Phase III	Australia, Hungary, Russia	IV / Infusion	AstraZeneca	27 Sep 2018
Urogenital cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Metastatic disease, Monotherapy	Phase III	Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Russia, South Korea, Spain, Taiwan, Turkey, USA, United Kingdom	IV / Infusion	AstraZeneca	01 Nov 2015
Urogenital cancer	-	Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease	Phase III	Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Russia, South Korea, Spain, Taiwan, Turkey, United Kingdom	IV / Infusion	AstraZeneca	02 Nov 2015
Urogenital cancer	in combination with tremelimumab	Combination therapy, First-line therapy, Inoperable/Unresectable, Metastatic disease	Phase III	Hungary	IV / Infusion	AstraZeneca	27 Sep 2018
Urogenital cancer	-	Late-stage disease, Monotherapy, Second-line therapy or greater	Phase I/II	United Kingdom	IV / Infusion	AstraZeneca, MedImmune	05 Jun 2016
Urogenital cancer	-	First-line therapy, Inoperable/Unresectable, Late-stage disease, Monotherapy	Phase Unknown	China	IV / Infusion	AstraZeneca	02 Nov 2015
Urogenital cancer	Urothelial cancer	Late-stage disease, Metastatic disease, Monotherapy, Second-line therapy or greater	Market Withdrawal	USA	IV / Infusion	AstraZeneca	22 Feb 2021
Uterine cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater	Phase II	USA	IV / Infusion	AstraZeneca	03 Jun 2016
Vulvovaginal cancer	-	Combination therapy, Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater	No development reported (I)	USA	IV / Infusion	AstraZeneca, M. D. Anderson Cancer Center	28 Aug 2022

Type	Region	Indication
Fast Track	USA	Head and neck cancer
Breakthrough Therapy	USA	Non-small cell lung cancer; Urogenital cancer

Indication	Patient Segment	Country	Organisation	Event Date
Biliary cancer	-	USA	AstraZeneca	17 Dec 2020
Biliary cancer	-	Australia		31 Mar 2022
Liver cancer	-	USA	AstraZeneca	20 Jan 2020
Small cell lung cancer	-	USA	AstraZeneca	12 Jul 2019

Adverse drug reaction	Total safety reports	Serious reports	First reports
Accidents injuries and poisoning	1	1	-
Behaviour and behaviour mechanisms	1	1	-
Cardiovascular disorders	77	75	-
Chemically induced disorders	8	6	-
Congenital disorders	5	4	-
Digestive system disorders	90	87	-
Disorders of environmental origin	2	2	-
Drug response related complications	84	84	-
Ear nose and throat disorders	5	5	1
Endocrine disorders	73	71	-
Eye disorders	26	26	1
Genitourinary disorders	30	29	2
Haematological disorders	53	47	-
Immunological disorders	89	83	-
Infections	36	32	-
Male urogenital diseases	1	1	1
Mental disorders	4	4	-
Multisystem disorders	5	5	-
Musculoskeletal disorders	59	56	-
Neurological disorders	88	85	1
Nutritional and metabolic diseases	33	33	-
Pathological conditions signs and symptoms	217	209	-
Pathology and biological functions	2	2	-
Pigmentation	11	8	1
Respiratory tract disorders	129	129	-
Sclerosis	6	6	-
Signs symptoms and ill defined conditions	34	31	-
Skin and connective tissue diseases	75	68	2
Stomatognathic disorders	5	5	-
Tissue disorders	6	6	1
Tumours	10	9	-

Scientific Summary

Pharmacokinetics

Dose-dependent durvalumab pharmacokinetic parameters were observed in patients with advanced solid tumours in a phase I 1108 study^[591]^[220].

Pooled analysis

The pooled pharmacokinetic exposure-efficacy analysis of the phase I/II 1108 trial and phase II ATLANTIC trial in patients with urothelial carcinoma (UC) and other solid tumours demonstrated that durvalumab 10 mg/kg IV q2w regimen had no association of pharmacokinetic (PK) exposure with efficacy or safety, overall. Distribution of PK metrics were similar between responders and non-responders. A few inverse trends were observed, and the association of ECOG and albumin versus PK exposure were also observed in the population PK modeling^[439]^[220]^[437].

Data from a phase I trial conducted in 19 evaluable patients with colorectal cancer and pancreatic cancer showed that dose-dependent increase in the exposure of pexidartinib from 400 to 1000 mg. Two DLTs (AST/ALT elevations including one with bilirubin increase) were seen at dose level of 1000mg/d^[620]^[621].

In a phase I trial of adavosertib in combination with durvalumab in patients with advanced solid tumors (n=54) preliminary pharmacokinetics at the dose 150 mg BID showed adequate coverage for cell kill activity and no drug–drug interaction^[606]^[607].

Updated results from the phase Ib trial demonstrated C_max and C_trough increased in a dose-proportional manner over the dose range of 1 to 3 mg/kg for tremelimumab Q3W. PK exposures for both durvalumab at 15 mg/kg, 1125mg, or 1500mg Q3W and tremelimumab at 1, 3 mg/kg, 56, and 75mg demonstrated accumulation after the administration of multiple doses. PK parameters did not differ across platinum-doublets^[582]^[583].

In the phase I/I PINCH trial, the pharmacokinetic profile confirmed visual prolonged tracer-retention in blood pool with increasing protein dose. PD-L1-expression was equally distributed amongst dose-groups. Tumour lesions were visualized best using 10 or 50mg durvalumab (SUV_peak 2mg: 3.86 ± 0.79, 10mg: 7.46 ± 2.18, 50mg: 5.57 ± 1.74). Tumour-to-blood-ratios for 10mg durvalumab were highest (2mg: 2.27 ± 0.33, 10mg: 3.44 ± 0.76, 50mg: 1.73 ± 0.99; p = 0.019)^[241]^[240].

Results from a phase I trial in patients with solid tumours and CNS cancer demonstrated that pharmacokinetics for DL2 in patients ≥35 Kg and < 35 Kg were comparable to pharmacokinetics in adults dosed with durvalumab 10 mg/kg IV Q2 weeks. Mean (SD) DL2 C_max 292 (102) mg/mL, C_trough 85.1 (27.7) mg/mL, AUC 2220 (986) day*mg/mL in patients ≥35 Kg and C_max 442 (338), C_trough 120 (123), AUC 2470 (1870) in patients < 12 years weighing < 35 kg^[602]^[600]

Results from phase I trial in solid tumours showed C_max was 6.3 Log10 copies/mL in the SD2 cohort following infusion. The levels of plasma IL-12 reached mean C_max of 143.79 and 168.93 pg/mL for SD1 and SD2, respectively, within 12 hours after infusion^[449]^[447].

Adverse Events

Head and neck cancer:

Phase III

The results from the phase III EAGLE trial in patients with squamous cell carcinoma of head and neck showed that the risk of death was not statistically significantly different for durvalumab (D) compared with standard chemotherapy (SOC) (HR: 0.88; CI: 95 % 0.72–1.08; P = 0.20) or the combination therapy of durvalumab and tremelimumab (D+T) versus SOC (HR: 1.04; CI: 95%, 0.85–1.26; P = 0.76). 10.1% of patients reported treatment-related adverse events (AEs) greater than grade 3 (regardless of causality grade ≥ 3 AEs were 41.4%) in the D arm, 16.3 % (51.2 %) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of patients in D, 5% in D+T and 15% in SOC received immunotherapy^[216]^[218]

Results from phase II CheckRad-CD8 trial showed that in treatment with combination of cisplatin/ docetaxel plus durvalumab/ tremelimumab one case of grade III-IV toxicity hepatitis and one infectious diarrhea was observed^[226]^[225]. Additional results from the trial demonstrated that the adverse events (AE) of grade 3-4 were reported in 39 patients (68%) and mainly consisted of leucopenia (43%) and infections (28%). 6 patients (11%) developed grade 3-4 immune-related AEs. Toxicity (treatment-related or un-related) ≥grade 3 appeared in 75 patients (95%) and mainly consisted of dysphagia (53%), leucopenia (48%) and infections (29%). DLT mainly consisted of hepatitis (10%), 10 received DLT and 4 discontinued for other reasons^[227]^[228].

In the phase III PACIFIC trial, treatment with durvalumab was generally safe and well tolerated in patients with non-small cell lung cancer (NSCL). Most frequent treatment-related adverse events (AEs) included cough (35.2% versus 25.2%), pneumonitis/radiation pneumonitis (20.2% versus 15.8%), fatigue (24% versus 20.5%), dyspnoea (22.3% versus 23.9%) and diarrhoea (18.3% versus 18.8%) as compared with placebo. Other most frequent adverse reactions reported were rash in 15.4% (n = 73), hypothyroidism in 10.5% (n = 50), diarrhoea 9.7% (n = 46) and interstitial lung disease 9.7% (n = 46) patients, respectively. Grade 3 or 4 AEs was reported in 30.5% versus 26.1% in placebo. In study group 15.4% of patients discontinued treatment due to AEs compared with 9.8% of placebo group, respectively. Treatment led to reduction in risk of death by 32% (HR 0.68, 99.73% CI 0.47-0.997; p = 0.0025). The results were reported from 713 patients recruited in a randomised, double-blind, placebo-controlled study^[414]^[415]^[332]^[416]^[418].

Durvalumab monotherapy and durvalumab and tremelimumab combination therapy was well tolerated in the phase III MYSTIC trial, conducted in 1 118 patients with stage IV non-small cell lung cancer. The number of deaths observed in durvalumab monotherapy arm, standard-of-care (SoC) chemotherapy arm were 108 (66.3%) and 128 (79.0%), respectively^[399]^[63]^[398].

Results from the phase III ARCTIC trial showed that grade ≥3 treatment-emergent AEs were 46.8%durvalumab+tremelimumab and 54.5% standard of care in SSB; 45.2% D and 66.7% SoC in SSA (sub study A group: SoC (as SSA); durvalumab (as SSA); or tremelimumab 10 mg/kg IV q4w for 24 weeks then q12w for 24 weeks), median)^[408]^[409].

Updated results from the phase III POSEIDON trial demonstrated that tremelimumab plus durvalumab and chemotherapy continued to be well-tolerated, with no new safety signals identified based on the collection of serious adverse events (AEs) during the approximately four-years of follow-up. Serious treatment-related AEs of any grade occurred in 27.6% of patients in the durvalumab, tremelimumab and chemotherapy arm versus 17.7% in the chemotherapy alone arm as assessed by investigators. Treatment-related AEs leading to death occurred in 3.3% of patients in the combination arm versus 2.4% in the chemotherapy arm ^[393]. Previous results demonstrated the safety profile of all regimens was manageable per standard guidelines and in line with the known profiles of D, T+D and CT; the most common grade 3/4 TRAEs were those typically associated with CT. As expected, more imAEs occurred with T+D+CT than D+CT, but the incidence of grade 3 or 4 imAEs, imAE-related deaths and treatment discontinuations due to imAEs was generally similar in the IO arms. T+D did not compromise the ability to administer planned CT. The most common grade 3/4 TRAEs were hematologic (anemia in 17%, 15% and 20% of pts in the T+D+CT, D+CT and CT arms and neutropenia in 16%, 13% and 12%) and most were managed using standard approaches per local practice; 22%, 18% and 16% of patients received colony stimulating factors and 22%, 21% and 26% received blood transfusions. All grade immune-mediated AEs (imAEs) occurred in 34%, 19% and 5% of patients in the T+D+CT, D+CT and CT arms; a higher incidence of diarrhea/colitis, dermatitis/rash and endocrinopathies was seen with the addition of T to D+CT. Grade 3/4 imAEs occurred in 10%, 7% and 2% of pts in the T+D+CT, D+CT and CT arms, and serious imAEs in 10%, 6% and 1%; imAEs led to discontinuation of any study treatment in 6%, 4% and 0.6%, and led to death in 0.6%, 0.3% and 0%. Most imAEs were low grade and manageable with systemic corticosteroids (received by 26%, 13% and 4% of patients in the T+D+CT, D+CT and CT arms) or endocrine therapy (12%, 8% and 1%). Median time from first dose to onset of imAEs (TTO) was generally > 60 days and the majority of non-endocrine imAEs resolved ^[389]. Updated results demonstrated that the safety profile of each durvalumab combination was consistent with the known profiles of the individual medicines, and no new safety signals were identified. Grade 3 or 4 treatment-related adverse events were experienced by 51.8% of patients treated with durvalumab, tremelimumab and chemotherapy and by 44.6% of patients treated with durvalumab plus chemotherapy, versus 44.4% for chemotherapy. Treatment-related adverse events led to treatment discontinuation in 15.5% of patients treated with durvalumab, tremelimumab and chemotherapy and 14.1% of patients treated with durvalumab plus chemotherapy, versus 9.9% for chemotherapy. Previous results from the phase III POSEIDON trial for durvalumab plus platinum-based chemotherapy or durvalumab, tremelimumab and chemotherapy versus chemotherapy alone in the first-line treatment of patients with stage IV metastatic non-small cell lung cancer (NSCLC) demonstrated that each combination had an acceptable safety profile, and no new safety signals were identified. Combination with tremelimumab delivered a broadly similar safety profile to durvalumab and chemotherapy combination and did not lead to an increased discontinuation of treatment^[390]^[391]^[392]^[388].

Results from a phase Ib/II trial in patients with HPV-associated recurrent/metastatic head and neck cancer, showed that MEDI 0457 in combination with durvalumab was well tolerated. At the interim analysis, of the 35 patients enrolled, 13 patients (37.1%) and 27 were response-evaluable. Treatment-related adverse events (TRAEs) occurred in 77.1% of patients, mostly of Grade 1–2 severity. Fatigue (37.1%) and injection site pain (34.3%) were most common. Five patients (14.3%) had Grade 3 TRAEs and 1 patient (2.9%) had 3 serious Grade 3 TRAEs (AST and ALT increased and myocarditis causing discontinuation). No patients had Grade 4/5 TRAEs. The trial is conducted in 50 patients with HPV-associated recurrent/metastatic head and neck cancer^[237]^[236].

Phase II:

Results from 12 evaluable patients with metastatic colorectal cancer in an open-label, single-group phase II trial showed that there were five grade three toxicities which included anaemia, fatigue, dehydration, peripheral neuropathy and thromboembolism. No grade 4 or 5 toxicities were reported^[187]. Updated results in 20 evaluable patients (of 33 enrolled) showed that grade 5 unexplained sudden death was reported in 3% of the patient; two had grade 4 (6%, colitis, dehydration, pneumonitis); and 12 had grade 3 (38%, primarily GI, other than colitis, and nutrition). The open-label, single-group trial evaluatee the safety and efficacy of tremelimumab and durvalumab following hypofractionated palliative radiation in patients with microsatellite stable metastatic colorectal cancer^[188]^[189].

Phase I/II

Results of phase I/IIa MEDITREME trial for induction therapy of durvalumab (750 mg/q2W), in combination with tremelimumab (75 mg/q4W) and FOLFOX (6 cycles), in patients with previously untreated RAS-mutated metastatic colorectal cancer (mCRC) showed that treatment-related grade 3-4 AEs occurred in 75%, of patients. Most frequent grade 3-4 AEs were gastrointestinal and haematological in nature, mainly related to chemotherapy and occurred during induction period^[182]^[181].

Phase I/II

Updated results in 191 evaluable patients reported fatigue (19.4%), decreased appetite (9.4%), diarrhoea (8.4%), rash (7.3%), nausea (6.8%), arthralgia (5.8%), pyrexia (5.8%) and pruritus (5.2%), as the most common AEs in ≥5% of the patients. 6.8% of the patients showed occurrence of grade 3 or 4 adverse events, and treatment was discontinued by three patients due to AEs. Earlier, follow-up preliminary results from the phase I/II Study 1108 of durvalumab showed that the most frequent treatment-related adverse events (AEs) were fatigue (18%), decreased appetite (9%), nausea (8%), rash (8%) and diarrhoea (8%); 5% of patients discontinued treatment due to AEs. The most common adverse events reported in ≥5% in the cohort of patients with squamous cell carcinoma of the head and neck (n = 62) were fatigue (18%), diarrhoea and nausea (8% each), pruritus, rash and maculopapular rash (7% each). 25 pts (10%) had treatment-related Grade 3/4 AEs, most frequent: fatigue and hyponatremia (each 2%). 4% had treatment-related serious adverse events including colitis and pneumonitis (each 2%). No treatment related deaths were reported. Among 40 patients with hepatocellular carcinoma, 80% of patients experienced AEs, including fatigue (27.5%), pruritus (25.0%) and elevated aspartate aminotransferase (AST) (22.5%) as the most commonly observed AEs. Grade 3–4 treatment-related AEs were experienced by 20.0% of patients, most commonly observed AEs were elevated AST (7.5%) and elevated alanine aminotransferase (5.0%). Seven patients completed the initial 12-month treatment and 7 patients discontinued treatment because of an AE (none related to treatment). There were no deaths due to treatment-related AEs^[587]^[669]^[668]^[589]^[590]^[248]^[220].

Results from the phase II DuTRe-raD trial, showed that treatment with durvalumab plus tremelimumab in combination with radiotherapy and durvalumab in combination with radiotherapy, was safe and generally well tolerated, in patients with non-resectable locally advanced head and neck cancer. The interim feasibility analysis of tremelimumab revealed that 5/6 patients stopped treatment, due to 1 grade 5 and 1 grade 4 immune related AE and 3 non-immune related AEs, respectively. Thus, the tremelimumab arm was prematurely terminated, and only the D monotherapy arm continued. Futility analysis of D monotherapy showed, one of 12 patients stopped treatment due to immune related toxicity, and 7 patients experienced disease progression on treatment or died within the first year^[231]. Earlier, data demonstrated that of 10 patients in arm D, (1500mg) 1 patient stopped infusional treatment due to immune related toxicity. Out of 6 patients in the DT arm (1500mg/75 mg), however, 5 patients stopped treatment due to treatment related adverse events (AEs), 2 patients due to immune related toxicity with one Grade 5 AE. Three patients stopped due to non-immune related AE. The grade 5 AE prompted the interim analysis, which revealed non-feasibility as well as safety-issues of the DT+radiotherapy combination. No increase in toxicity was observed in the D monotherapy arm^[230]^[229].

Preliminary results from the phase I/II trial demonstrated that durvalumab (10mg/kg) had a manageable safety profile among all patients (n=61). The most common adverse events reported in 5% or more of patients were all grade 1 or 2: fatigue (13%), diarrhoea (10%), decreased appetite (8%), arthralgia (7%), asthenia (7%), nausea (7%) and pyrexia (7%). Treatment-related Grade 3 adverse events were experienced by 3 patients (1 acute kidney injury, 1 infusion-related reaction and 1 tumour flare)^[586]^[220].

Updated data from the phase Ib/IIa SCORES trial indicated that the safety profile of second line therapy with durvalumab, in combination with danvatirsen (AZD 9150) [see Adis Insight Drug Profile 800021483], in PD-L1 naive patients (n = 38), was consistent with previous results. Adverse events (AEs) included transaminase elevations and thrombocytopenia, which were manageable and reversible. Causally related AEs occurred in 76% PD-L1 naive patients (n = 20), on treatment with durvalumab in combination with AZD 5069 (CX2i) [see Adis Insight Drug Profile 800030696]^[249]. Earlier results reported mild increase in a liver enzyme, mild decrease in platelet count and mild anaemia following treatment with AZD 9150 in combination with durvalumab, in treatment-naive patients (n = 28) with head and neck cancer. Thrombocytopenia (64%), neutropenia (45%) and ALT/AST increase (36%) were the most common drug related adverse events in patients with late-stage solid tumours on treatment with AZD 9150 in combination with durvalumab. There were no dose-limiting toxicities (DLT) or The open-label, randomized trial is designed to enrol a total of 465 patients^[681]^[248]^[246].

In a phase I/II study, treatment with durvalumab in combination MEDI 0680 in patients with cancer resulted in grade 3 dose-limiting toxicity in 1 patient of bladder cancer cohort. The most common drug-related adverse events were pruritus (17%); diarrhoea and fatigue (both 13%); and flushing, peripheral oedema, and pyrexia (each 10%). Immune-related adverse events were similar to those observed with other checkpoint blockade agents. Discontinuation of treatment was observed in 7% patients. No deaths were reported. The maximum tolerated dose was not reached. Results were reported from 30 patients enrolled in an open-label study^[617]^[616].

In a phase I/II DREAM trial in patients with malignant pleural mesothelioma, durvalumab demonstrated acceptable tolerability. Thirty-one patients (57%) reported grade 3 or higher grade adverse events (AEs). Nineteen patients (35%) had immune-related (ir) AEs including two grade 3 irAEs^[312]^[313].

In a phase II trial being conducted in patients with glioblastoma, treatment-related adverse events with maximum CTCAE grade ≥ 3 occurred in 14 of patients; the most common were asymptomatic increased lipase (n = 6) and increased amylase (n = 2). Twenty-four of 40 patients were alive at 12 months (Kaplan-Meier for OS12, 60.0% [90% CI: 46.1, 71.4]). Median OS was 15.1 (95% CI: 12.0, 18.4) months. 8 patients remain alive, with ongoing survival ranging from 15.7 to 34.9 months. Earlier, the treatment-related adverse events (TRAEs) by max CTCAE grade (Gr) were Gr1: 35.5%; Gr2: 41.9%; Gr3: 9.7%; and Gr4/5: 0%. Most commonly reported adverse events included (≥3 pts) fatigue, headache, hemiparesis, gait disturbance, increased AST, and decreased platelets/WBCs/lymphs. The trial is being conducted in 159 patients with glioblastoma^[259]^[260]^[258].

Treatment with ibrutinib (560 mg, daily) + durvalumab, 10 mg/kg every two-week, led to a favourable safety profile in patients with solid tumours, in a phase Ib/II trial. Clinically meaningful differences in the safety profile were not observed across tumour types, except differences due to tumour type, location, and prior therapies. Grade ≥3 treatment-emergent adverse events that occurred in ≥5% of patients included hyponatraemia (10%), dyspnoea (7%), maculopapular rash (7%), pneumonia (7%), anaemia (6%) and diarrhoea (6%). The open–label trial enrolled 124 patients^[579]^[581].

Updated results from phase I/II trial in 33 evaluable patients with head and neck squamous cell cancer demonstrated that the recommended median and maximum SBRT doses were 45 Gy (18–50) and 52.3 Gy (28–69) in 3-5 portions, respectively. As a result of D and T, 14 patients (42%) suffered Grade 3 AE. SBRT was only partially responsible for one patient's Grade 3 AE. In particular, this patient, who had mucosal radionecrosis following reirradiation and declined surgical debridement and flap restoration, experienced two Grade 3, one Grade 4, and one Grade 5 AE^[245]. Initial results of the open-label phase I/II trial in 16 evaluable patients with oligometastatic head and neck carcinoma demonstrated tolerable profiles to the triple treatment combination (TTC) of durvalumab 1 500 mg plus tremelimumab 75mg plus stereotactic body radiotherapy (SBRT). There were one CTCAE V5.0 grade 2 and 1 grade 3 (both GI) serious adverse event (SAE) attributable to durvalumab and tremelimumab. Two patients had unrelated SAEs (one grade 3-hypercalcemia and one grade 5 - GI). The grade 5 SAE was a gastric haemorrhage that occurred the night of the first durvalumab plus tremelimumab infusion. There was no grade 3+ AE secondary to SBRT. The SBRT did not add to the 2/16 patients who had durvalumab plus tremelimumab related SAEs^[244]^[243].

Phase I:

Long-term follow-up results of the open-label, phase Ib dose-escalation trial of durvalumab, in combination with tremelimumab [see AdisInsight drug profile 800020650], demonstrated a good safety profile in patients with advanced non-squamous NSCLC. The most common treatment-related adverse events (AEs) were fatigue (19%), pruritus (17%), diarrhoea (15%), reduced appetite (14%) and rash (14%). A treatment-related AE was experienced by 14 patients (7%) that caused treatment discontinuation, and 23% experienced a grade 3/4 treatment-related AE. There was one treatment-related death due to multifactorial hypoxia^[457]. Interim results showed that the overall adverse events (AEs) were manageable and generally reversible with standard treatment. Across all dose cohorts, the most frequently reported treatment related AEs (grade 3/4) were colitis, diarrhoea, and elevated lipase and elevated liver function tests. Of 102 patients, 20 stopped the study due to drug-related AEs. One related grade 3/4 adverse events (AE) was observed in 30% patients and 16% discontinued treatment due to a related adverse event^[458]^[300]^[456].

In a phase I study of durvalumab plus dabrafenib and/or trametinib in patients with malignant melanoma, overall adverse events were consistent with known safety profiles of the combination components. No exacerbation of immune-related AEs was noted^[300].

According to phase I data, durvalumab has demonstrated an acceptable safety profile in patients with advanced solid tumours^[406]^[673]. Drug-related AEs at grade 3 or higher occurred in 8% of patients with NSCLC, and in 10% of patients with SCCHN^[300]. Immunogenicity occurred infrequently (2 of 196 patients), and had no effect on the pharmacokinetic or pharmacodynamic profiles of durvalumab (Study 1108)^[591].

Phase I/II

In the phase I/II PINCH trial, no adverse events were reported^[241]^[240].

Administration of ramucirumab and durvalumab in a phase I trial in patients with solid tumours including non- small cell lung cancer, gastric/gastroesophageal junction cancer and hepatocellular carcinoma was found to be generally safe and well tolerated. Hypertension (14.3%, 17.2%, 17.9%), anemia (3.6%, 24.1%, 21.4%), and fatigue (10.7%, 10.3%, 10.7%) were the most commonly observed grade 3/4 treatment-emergent adverse events (AEs). For ramucirumab, grade 3/4 AEs of special interest included hypertension, bleeding events (3.6%, 10.3%, 10.7%) and venous thromboembolic events (0%, 10.3%, 7.1%) while for durvalumab increase in lipase (10.7%, 3.4%, 10.6%) and AST (3.6%, 3.4%, 17.9 %) were the grade 3/4 AEs of special interest^[604]^[603].

Results from the phase II expansion cohort (cohort 3) of the phase I/II trial demonstrated that the safety of the chemotherapy free triplet combination of monalizumab, cetuximab and durvalumab regimen was acceptable with a low rate of discontinuation as first-line treatment of R/M SCCHN ^[559]. In updated results from a phase I trial, monalizumab in combination with durvalumab was safe and well tolerated. Of 18 patients enrolled (as of March 2019) monalizumab-related adverse events (AEs) occurred in 13 (72%), serious in one (6%; embolism). Durvalumab related AEs occurred in 14 (78%; none serious). All patients had chemotherapy-related AEs, serious in and (6%; febrile neutropenia) and 10 (56%) had bevacizumab-related AEs, serious in two (11%; embolism and febrile neutropenia). There were no grade 5 or dose-limiting toxicities. At 16 weeks, 17 patients were evaluable for response; nine (53%) had partial responses (seven confirmed, two unconfirmed), six (35%) had stable disease and two (12%) had progressive disease; there were no complete responses. Earlier, in 40 evaluable patients, the safety profile of monalizumab and durvalumab combination was consistent with the monotherapy profiles of each agent. In the microsatellite-stable colorectal cancer (MSS-CRC) expansion cohort, arthralgia (7.5%), increased aspartate transaminase (AST) (7.5%), hypothyroidism (7.5%), pruritus (7.5%), and rash (7.5%) were the most common treatment-related adverse events (AE). Grade 3/4 AEs observed in three patients were restricted to sepsis (n=1, grade 4) and increased lipase (n=1, grade 3), which were resolvable, and increased AST (n=1, grade 3)^[552]^[553]^[554]^[557].

Treatment with 20 mg/kg durvalumab, in combination with 1 mg/kg tremelimumab, was safe and generally well tolerated in patients (n=30) with advanced solid tumours (extensive disease small-cell lung cancer), in a phase I trial. Out of 30 evaluable patients, 20 of them (67%) were reported ≥1 treatment-related adverse events (TRAEs). The most common AEs were fatigue (n=7 [23%]) and pruritus (n=7 [23%]). Additionally, seven patients (23%) had grade 3/4 TRAEs. No patients were discontinued due to TRAEs and there were no treatment-related deaths reported^[612]^[611].

Final results of the phase Ib/II CALGB 80803 study showed that addition of adjuvant D to induction FOLFOX and PET-directed CRT prior to surgery was safe^[207]^[206].

Pooled analysis

The pooled pharmacokinetic exposure-safety analysis of the phase I/II 1108 trial and phase II ATLANTIC trial in patients with urothelial carcinoma (UC) and other solid tumours observed that durvalumab 10 mg/kg IV q2w regimen was a well tolerated dose as single agent in UC patients, and no association of pharmacokinetic (PK) exposure with safety, overall. A higher PK exposure was not associated with an increased risk of AE, for grade 3+ AE (all types) and AE leading to treatment discontinuation (p-value ranged from < 0.00005 to 0.88; n = 158, 929 and 434 for study 1108 UC cohort, study 1108 all patients and ATLANTIC all patients, respectively)^[439]^[220]^[437].

Phase II: In the phase II NIBIT-MESO-1 trial, the combination of tremelimumab and durvalumab was safe and manageable in malignant mesothelioma patients. Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity)^[666]^[314].

In the phase II BALTIC trial in patients with platinum refractory or resistant extensive-stage SCLC, the combination of durvalumab with tremelimumab demonstrated a tolerable safety profile. Grade 3 or higher adverse events (AEs; all cause) were reported in 10 patients (48%), of which 4 patients (19%) experienced an event deemed possibly causally related to treatment by the investigator. One patient (4.8%) discontinued due to a possibly causally related AE^[539]^[538].

Interim data from 40 patients from a phase I/II study demonstrated that the most common (≥15%) treatment-related AEs were fatigue (20%), increased ALT (18%), pruritus (18%), and increased AST (15%). The most common grade ≥3 related AE was asymptomatic increased AST (10%). There have been 24 discontinuations in the study, 3 due to treatment-related AEs (grade 3 pneumonitis, grade 3 colitis/diarrhoea, asymptomatic grade 4 elevated AST and ALT), 16 due to progressive disease, 4 due to death unrelated to treatment (cardiac arrest, variceal bleed, progressive disease, probable HCC rupture), and 1 other (patient entering hospice care)^[667]^[289].

Treatment with durvalumab alone, and in combination with tremelimumab, was generally well toletared in patients (n=267) with recurrent or metastatic head and neck cancer, in the phase II CONDOR trial. Treatment-related adverse events of any grade were highest for durvalumab alone (63.1%), followed by durvalumab+tremelimumab (57.9%) and tremelimumab alone (55.4%). Grade 3 or 4 event rates were reported highest for tremelimumab (16.9%), followed by durvalumab+tremelimumab (15.8%) and durvalumab (12.3%). Out of 267 evaluable patients, 12 patients were discontinued the therapy due to a treatment-related adverse event, including seven patients in the combination arm and five in the tremelimumab monotherapy arm. Furthermore, one death in the combination therapy group was associated with treatment^[238]^[221].

Treatment with azacitidine in combination with durvalumab for the treatment of acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS) indicated that the most frequent TEAEs (≥15%) were hematologic and GI toxicity. In the MDS and AML cohorts, 7 and 17, respectively, immune-mediated AEs were observed, all of which were treated and resolved. The data was released from 213 patients enrolled in a phase II FUSION HR MDS/ELDERLY AML 001 trial^[101]^[102].

Prostate cancer

Phase II:

Results from the phase II study reported grade 2 or less adverse events including fatigue (46%), anorexia (28%), rash (24%), diarrhea (23%), nausea/vomiting (21/18%) and thyroid dysfunction (15%). Most common grade 3/4 adverse events were LFTs (8%) and diarrhea (8%). Six patients discontinued treatment due to AEs. There were no grade 5 AEs^[511]^[512].

PhaseI/II: Durvalumab in combination with motolimod was generally well tolerated in a phase I/II study in patients with recurrent, platinum-resistant ovarian cancer. The most frequent (in ≥25% pts) treatment-emergent adverse events (AEs, all causality) were palmar-plantar erythrodysesthesia syndrome (PPES)/rash, stomatitis, fatigue, abdominal pain, nausea, pyrexia, and vomiting. Grade 3 treatment-related AEs in ≥ 2 pts included PPES/rash, stomatitis, lymphocyte count decreased, lipase increased, and anemia. The data is reported from 40 patients enrolled in the phase II of the study^[485]^[484]

Treatment of durvalumab and tremelimumab was well tolerated in a phase I/II trial conducted in metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma Eight (42%) patients showed TEAEs, four (21%) patients showed grade 3/4 AEs including fatigue, elevated lipase, decreased appetite, and interstitial lung disease, the latter of which led to treatment discontinuation. Drug related deaths were not observed^[211]^[210].

Data from a phase I trial conducted in 19 evaluable patients with colorectal cancer and pancreatic cancer showed that the the most frequent related (to either durvalumab, pexidartini or both) AEs were fatigue, maculopapular rash/pruritus/dry skin, hair colour changes, anorexia, oedema (periorbital, limbs or face), AST/ALT increases, bilirubin increases, nausea, vomiting and diarrhoea. The most frequent grade ≥ 3 AEs related to pexidartini were AST/ALT increase, ALP increase, neutrophil or white blood cell count decrease, and fatigue^[620]^[621].

In a phase I trial of adavosertib in combination with durvalumab in patients with advanced solid tumors (n=54) adverse events were grade ≥3 in severity, fatigue (15%), diarrhea (11%) and nausea (9%) were commonly reported. Dose limiting toxicities (DLTs) were nausea (n = 2) and diarrhea (n = 1). Serious adverse events were reported in seven patients (13%) including reversible and confounded drug-induced liver injury^[606]^[607].

Endometrial cancer

Phase III:

The updated results from the phase III DUO-E trial demonstrated that the safety profiles of the treatment arms (carboplatin/paclitaxel (CP) in combination with durvalumab and carboplatin/paclitaxel (CP) in combination with durvalumab and Olaparib) were generally consistent with individual components^[199]. The previous results of phase III DUO-E trial of durvalumab (Imfinzi) demonstrated consistent safety profile in patients with advanced or recurrent endometrial cancer. The most common adverse events (AEs) reported in the Imfinzi plus Lynparza Arm during the overall study were anaemia (62%), nausea (55%), fatigue and asthenia (54%), alopecia (51%), neutropenia (42%), constipation (33%), thrombo-cytopenia (30%), diarrhoea (28%), vomiting (26%), peripheral neuropathy (25%), peripheral sensory neuropathy (25%), arthralgia (24%), decreased appetite (23%), leukopenia (20%) and urinary tract infection (20%). The most common AEs reported in the imfinzi arm during the overall study were alopecia (50%), anaemia (48%), fatigue and asthenia (43%), nausea (41%), neutropenia (36%), diarrhoea (31%), arthralgia (30%), thrombo-cytopenia (28%), constipation (27%), peripheral neuropathy (26%), peripheral sensory neuropathy (26%) and vomiting (21%)^[198]^[197]

Phase

II: Interim results from the phase II trial demonstrated no significant safety signals. Most common treatment-related adverse events were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Grade 2 TRAE were seen in two patients in durvalumab arm while in 9 patients in the combination arm. Grade 4 TRAE were see in one patient in durvalumab arm and in 3 patients in the durvalumab plus tremelimumab treated arm ^[648]^[647].

Sarcoma:

Results from a phase II trial in patients with sarcoma subtypes showed that grade ≥3 related adverse events were experienced by 14 patients (24.6%) which included colitis, nausea, cardiac dysfunction, thyroiditis, pneumonitis, hepatitis, myositis, anemia and fatigue. The results were reported from 57 patients^[630]^[629]

Small cell lung carcinoma:

Phase III

In a phase III NEPTUNE study, tolerability and safety for the combination of durvalumab and tremelimumab was consistenst as from previous trials^[402]^[401].

Self-reported data from patients (n=164) in phase III CASPIAN trial with extensive stage small cell lung cancer baseline adverse events rates were generally maintained in both arms up to 24 weeks after starting treatment, except for itchy skin, which showed a numerical increase from 13% at baseline to a peak of 34% at cycle 6 in the durvalumab plus platinum-etoposide (EP) arm and 12% at baseline to a peak of 42% at cycle 8 in the platinum-etoposide (EP) arm; and dizziness, which showed a numerical increase from 16% at baseline to a peak of 40% at cycle 5 in the durvalumab plus platinum-etoposide arm, while rates were maintained vs baseline in the EP arm. Most patients reporting these AEs indicated that they occurred rarely or occasionally, or were mild or moderate in severity^[536]. Treatment of IMFINZI plus chemotherapy showed a well-tolerated safety profile in a phase III CASPIAN trial in patients with extensive stage small cell lung cancer. Results showed 32.5% of patients experienced a serious adverse event (all causality) with IMFINZI plus chemotherapy versus 36.5% with chemotherapy alone. No patients tested positive for treatment-emergent anti-drug antibodies to durvalumab^[529]^[524]. Patients with greater exposure to durvalumab had numerically higher rates of immune-mediated AEs^[414]. Interim results showed incidence of all cause adverse events of grade 3/4 was 62.3%, 70.3% and 62.8%, those leading to discontinuations was 10.2%, 21.4% and 9.4%, and those leading to death was 4.9%, 10.2% and 5.6%, for the durvalumab plus platinum therapy, durvalumab plus tremelimumab plus platinum therapy, and platinum therapy alone cohorts, respectively. The most common adverse reactions were nausea, fatigue/asthenia and alopecia^[665]^[530]^[520]^[531]^[533].

In the phase III DANUBE trial, durvalumab + tremelimumab combination therapy, added to standard of care (SoC) chemotherapy showed consistant safety and tolerability profile as reported previously. Treatment-related adverse events of grade 3–4 occurred in 14%, 28%, and 60% of patients in the durvalumab, durvalumab plus tremelimumab, and chemotherapy arms, with deaths possibly related to treatment in 0.6%, 0.6%, and 0.3% of patients, respectively^[85]^[83]^[84].

Phase III:

Results from the study of durvalumab (D) plus platinum-etoposide (EP) in first-line treatment of extensive-stage small cell lung cancer (CANTABRICO) showed that durvalumab was well-tolerated. Only 5 patients discontinued study treatment due to toxicity and all during EP+D phase namely neurotoxicity, multiple sclerosis, nephritis and pneumonitis. Most frequent adverse events ≥G3 were anemia (22%), neutropenia (20%), thrombocytopenia (6%) and hyponatremia (5%)^[324]^[323].

Phase II:

In the phase II trial, treatment with durvalumab in combination with tremelimumab , grade ≥ 3 adverse events were reported, which included cytopenia (n = 4), dyspnea (n = 1), and endocrine disorders (n = 3) in Arm A; diarrhea (n = 3) and cytopenias (n = 1) in Arm B^[541]^[542].

In the phase II trial, treatment with tremelimumab in combination with durvalumab (arm A) had grade 3/4 treatment-related adverse events (TRAEs) occurred in 8 patients (20%). TRAEs led to treatment discontinuation in 5 patients (12%) and death in 1 patient (hemorrhagic enterocolitis)^[540]^[538].

Breast cancer:

Phase I/II:

Results from phase I/II neoadjuvant trial of durvalumab for the treatment of breast cancer showed that there are subsets of circulating inflammatory cytokines that may be associated with treatment emergent adverse events in patients with triple negative breast cancer (TNBC) treated with durvalumab concomitant with standard of care chemotherapy. Pielous diversity index showed no difference between patient groups for TCR (P>0.319). Baseline samples had increased sCD40L, EGF, and IL-10 in patients with RD compared to pCR (P< 0.05). Baseline samples had decreased FGF2 and IFN gamma in patients with immune related TEAEs compared to those with no immune related TEAEs (P< 0.05). Comparison of Pre-vs Post-treatment revealed that EGF, MIP1 alpha, IL-1 alpha, IL-8, and MDC were increased in patients with pCR compared to those with RD. Comparison of Pre-vs. Post-also revealed increased levels of cytokines (EGF, IL-7, IFN gamma, GM-CSF) in samples in patients with immune related TEAEs (P< 0.05) compared to those patients without immune-related TEAEs. It also revealed that there was an increase in a subset of cytokines (IL-7, IL-4, MCP3, and IL-1 alpha) in patients that presented with serious immune related TEAEs (P< 0.05) compared to those patients without serious immune-related TEAEs^[157]. Updated safety data from phase I/II neoadjuvant trial of durvalumab for the treatment of breast cancer showed that the incidence of immune-related adverse events (irAEs) was similar between African American (AA)and non-AA patients and no significant associations were found between irAEs and pathologic response. 3 patients completed therapy at the 3 mg/kg dose without any dose limiting toxicities (DLT), 1 patient refused further study medication because of recurrent gr 2 fatigue after 7 weeks of therapy. At the 10 mg/kg dose level, all 3 patients completed the nab-paclitaxel+durvalumab treatment without any DLT and 2 patients also completed 3 of the 4 planned treatments with dose dense doxorubicin/cyclophosphamide (ddAC) without DLT. Among all 7 patients who started therapy, 1 at the 3 mg/kg group experienced gr 3 dehydration and dyspnea without chest X ray abnormalities which resolved within 48 hours with hydration. There were no other gr 3 AEs. Among the 3 patients who have completed therapy as per protocol (not including the patient who withdraw consent), 1 achieved pCR, 1 had minimal, and 1 had extensive residual cancer. No surgical AE were seen^[156]^[154]^[155].

Administration of durvalumab in combination with paclitaxel in a phase I/II trial in patients with breast cancer was found to be generally safe and well tolerated. There were no reports of dose limiting toxicities. There were reports of two deaths due to progression of disease, while the patients receiving combination therapy are still alive. Anemia (25%), neutropenia, and leukopenia (20% each) were the most commonly observed adverse events irrespective of the grade. Additionally, neuropathy, and dyspnea were seen in 15% of patients (each). Neutropenia, leukocytopenia, headache, fatigue and abdominal pain were the grade 3/4 adverse events. One patient reported grade 2 colitis^[151]^[152].

Results from a phase I/II SYNERGY trial showed that the addition of oleclumab to the combination of chemotherapy by carboplatin and paclitaxel with durvalumab as first-line therapy for advanced or metastatic triple-negative breast cancer (mTNBC) demonstrated an acceptable toxicity profile. Grade 3-4 adverse events (AE) occurred in 28/33 patients (84.9%) in arm A and 21/35 patients (60.0%) in arm B (p=0.03). Most common grade 3-4 AE were hematological toxicities with neutropenia (arm A 17/33 [51.5%]; arm B 12/35 [34.3%], and anemia (Arm A 5/33 [15.2%]; 1/35 [2.9%] in Arm B). There was no increase of immune-related AEs in the arm A with oleclumab^[634]^[633].

In the phase II Apache trial, any-grade adverse events (AEs) were experienced in 34.5% of patients (n=10), without differences between arm A and B. The open-label, randomized trial enrolled 29 patients with advanced germ cell tumors (11 arm A and 18 arm B)^[642]^[640].

Results from phase I/II MOVIE trial showed that, twenty-two (73%) patients had grade ≥2 treatment-related adverse events (TRAE), including 11 patients (37%) with grade ≥3. Immune-related AE included colitis (2 G2, 2 G3), thyroiditis (7 G2). No toxic death was recorded. In previous results, sixteen patients (51.6%) had grade (G) =3 treatment-related adverse events (TRAE), including 11 pts with immune-related TRAE (35.5%) and 16 pts (51.6%) with chemotherapy-related TRAE. No toxic death was recorded^[571]^[570]. In phase I/II MOVIE trial, oral vinorelbine (MOV) combined with tremelimumab (T) and durvalumab (D) demonstrated toxicity profile consistent with earlier reports. From 16 patients with advanced breast cancer, 11 (69%) had grade ≥2 treatment-related adverse events (TRAE), including six patients (38%) with grade ≥3. Immune-related AE included colitis (1 G2, 2 G3), thyroiditis (8 G2). No toxic death was reported. In results from 14 patients, two (14.3%) at (dose-level) DL1=30 mg, 4 (28.6%) at DL2=40 mg and 4 (28.6%) at DL-1=20 mg patients had grade (G) 3 or higher adverse events (AEs) related to MOV, D and T, respectively. Immune-related AEs included colitis (1G2, 1G3), rash (2G1, 1G3), and thyroiditis (2G1, 3G2). No toxic deaths were recorded^[568]^[569]^[567].

Updated results of the open-label, randomized, phase Ib/II BEGONIA trial to determine the efficacy and safety of durvalumab, in combination with paclitaxel (P), plus capivasertib (C), plus oleclumab (O) demonstrated manageable safety and compelling high. Nausea and stomatitis were the most common adverse events (AEs; 40 [65%] each). Any Grade (G) 3/4 AEs occurred in 35 (57%) patients and serious AEs in 14 (23%). Low rates of anemia (9 [15%]), diarrhea (8 [13%]), and neutropenia (3 [5%]) occurred. Adjudicated treatment-related interstitial lung disease/pneumonitis occurred in 3 (5%) patients (2 G2; 1 G1). No deaths due to treatment-related AEs occurred. 10 (16%) patient discontinued any study drug due to AEs. No new safety signals were reported^[150]. Earlier, safety profiles of triplet combinations (D+P+C, D+P+O) in arms 2 and 5 were consistent with the individual agents in patients with untreated, unresectable, locally advanced or metastatic triple negative breast cancer. In arm 2, there was a relatively high rate of G3/4 treatment-relatedAEs but a low discontinuation rate for AEs. In arm 2 (data cutoff March 2021), 30 patients received D+P+C (15 P[80], 15 P[90]; total 13 ongoing), two patients (6.7%) discontinued all treatment due to AEs. The rates of dose delays were 13 patients (43%) for durvalumab and 15 (50%) for P; dose interruptions were one (3%) for durvalumab, 12 (40%) for paclitaxel, 15 (50%) for capivasertib ; dose reductions were 12 (40%) for paclitaxel and 14 (47%) for capivasertib. Treatment-related (tr)SAEs and G3/4 trAEs were experienced by seven (23%) and 22 (73%) patients . In Arm 5 (data cutoff Sep 2020), 33 patients received D+P+O (14 ongoing); no patients discontinued due to AEs. The rates of dose delays were 13 patients (39%) for durvalumab, 10 patients (30%) for paclitaxel, 10 patients (30%) for oleclumab; dose interruptions were 2 (6%) for durvalumab, 10 (30%) for paclitaxel, three (9%) for oleclumab; and dose reductions were 12 (36%) for paclitaxel. Treatment-related SAEs and G3/4 Treatment-related AEs were experienced by one (3%) and five (15%) patients. In both arms, there were no DLTs or deaths due to AEs^[148]. Interim results from the phase I/II BEGONIA trial, treatment with combination therapy durvalumab (D) and paclitaxel (P) demonstrated any grade 3/4 adverse events (AEs) and serious AEs in 44% and 4% of patients, respectively with breast cancer. Two patients discontinued treatment due to AEs. Patients receiving D+T-DXd reported any grade 3/4 AEs and SAEs in 36%and 9% of patients, respectively. No DLTs with one Grade 1 troponin increase reported^[147]^[146].

Phase I:

Results from a phase I trial in breast cancer treated with durvalumab and eribulin demonstrated no dose-limiting toxicities (DLTs) experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anaemia, AST and alkaline phosphatase elevation, hyperglycaemia, and nausea; most were grade 1/2. There was one immune-related AE of grade =3 (hepatitis). Three patients discontinued study drug related to toxicity [neutropenia (n = 1), hepatic toxicity (n = 2)]^[160]^[161].

Treatment with PVX 410 with durvalumab (DUR) in a phase Ib trial for breast cancer showed that among 20 evaluable patients for week 14 immune response, all planned PVX doses were given, and 1 DUR dose was held due to toxicity. No dose limiting toxicities (DLT) were observed in the six patient run-in. With a median follow up of 15.4 months, 18% patients had recurrence and 9% died. The most common adverse events were injection site reaction (96%), flu-like symptoms, fatigue (41% each), arthralgia, pruritis (36% each), alanine transaminase (ALT) elevation (32%), myalgia (27%), pain, diarrhea, aspartate transaminase (AST) and amylase elevation (23% each). Also, one patient had grade 3 diarrhea and one had grade 3 hyponatremia, AST and ALT elevation. There were no grade 4 or 5 events^[164]^[165].

In a phase I trial, treatment with the combination therapy of durvalumab and trastuzumab, reported no dose limiting toxicities at dose level 1 (n=6) or dose expansion (n=9) during cycle 1, in patients with breast cancer. One patient developed ≥ grade 3 irAE (grade 4 diabetes mellitus)^[167]^[166].

Updated results from the phase Ib trial demonstrated immune-related adverse events of </= grade 2, the most common of which were skin (38%), diarrhea/colitis (29%), and hypothyroidism (18%)^[582]^[583].

In the phase II MEDIOLA study in patients with ovarian cancer, the commonly reported adverse events of Grade 3 or above were anaemia, increased lipase and neutropenia, in the olaparib plus durvalumab cohort, and anaemia, hypertension, fatigue, increased lipase and neutropenia, in the olaparib plus durvalumab plus bevacizumab cohort. Adverse event related treatment discontinuation was reported in 6% (n=2) and 16% (n=5) patients in the olaparib plus durvalumab, and olaparib plus durvalumab plus bevacizumab cohorts, respectively. In previously reported results, the most common adverse events ≥Grade 3 were anemia (Grade 3, 4 patients), neutropenia (Grade 3, 3 patients), and pancreatitis (Grade 3, 1 patients, Grade 4, 1 patients)^[664]^[548]^[549].

Combination studies

Results from phase III MATTERHORN trial demonstrated grade 3 or higher adverse events from all causes were similar between the two arms, occurring in 69% of patients treated with the durvalumab-based regimen versus 68% for neoadjuvant chemotherapy alone^[204]. Results from the phase III MATTERHORN trial showed treatment with durvalumab added to standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) neoadjuvant (before surgery) chemotherapy demonstrated that the safety and tolerability of adding durvalumab to neoadjuvant FLOT chemotherapy was consistent with the known profile of this combination and did not decrease the number of patients able to undergo surgery versus chemotherapy alone^[663]^[202].

Updated results of the open-label, randomized, phase Ib/II BEGONIA trial of durvalumab for the treatment of breast cancer demonstrated that adverse events (AEs) were consistent with the agents known safety, with treatment-related AEs occurring in 49 patients (88%), any Grade 3/4 AEs in 18 patients (32%), and any serious AEs in 10 patients (18%). The most common all-Grade AEs were nausea (41 [73%]), fatigue (26 [46%]), and vomiting (17 [30%]). Adjudicated treatment- related interstitial lung disease/pneumonitis occurred for 5 patients (9%), which were mostly Grade 1 or 2 and 1 case of Grade 5 associated with COVID pneumonia. Seven patients (13%) and 21 patients (38%) had T-DXd dose reduction and dose delay, respectively; 22 (39%) had D dose delay. Seven patients (13%) discontinued treatment due to AEs^[149]. In the phase I/II BEGONIA trial, the safety profile of datopotamab deruxtecan in combination with durvalumab was consistent with the known safety profiles of both agents. The most common all-Grade TEAEs occurring in 20% or more of patients were nausea (57.4%), stomatitis (55.7%), alopecia (45.9%), fatigue (39.3%), constipation (39.3%), rash (27.9%) and vomiting (21.3%). Serious TEAEs were observed in 10 patients (16.4%). Treatment discontinuations due to an adverse event occurred in four patients (6.6%). No dose-limiting toxicities were reported. Two cases (3.3%) were adjudicated as treatment-related Grade 1 interstitial lung disease (ILD)^[129]^[680]. In the phase I/II BEGONIA trial, treatment with combination therapy durvalumab (D) and paclitaxel (P), demonstrated any grade 3/4 adverse events (AEs) and serious AEs in 44% and 4% of patients, respectively with breast cancer. Two patients discontinued treatment due to AEs. Patients receiving D+T-DXd reported any grade 3/4 AEs and SAEs in 36%and 9% of patients, respectively. No DLTs with one Grade 1 troponin increase reported^[147]^[146].

Phase I

Updated results from phase I STELLAR-001 trial demonstrated that the combination of avdoralimab and durvalumab was well tolerated in patients (n = 46) with advanced solid tumours. The most frequent adverse events (AEs) were asthenia (50%), cough (24%) and pruritus (24%), 11 pts (24%) reported AEs Grade 3 or higher, the most frequent was dyspnea (4%). A total of 31 (67%) pts experienced AE considered as related to avdoralimab, the most frequent were diarrhea, fatigue and pruritus (11% each). Serious related AEs were reported in 3 (6.5%) pts (colitis, liver injury, infusion related injection). Discontinuation rate due to an AE was 8.7%. In earlier data from 11 patients,1, no drug related toxicities were reported. Treatment related adverse events (TRAEs) were reported in five patients out of eleven patients. Grade two adverse events like diarrhea with lymphocytic colitis (n = 1) and grade one adverse events like diarrhea (n = 1), skin rashes (n = 2), white blood cell decrease (n = 1), pneumopathy (n = 1), lung disorder (n = 1), fatigue (n = 1), arthralgia (n = 1), back pain (n = 1), musculoskeletal chest pain (n = 1). No grade three or four TRAEs were reported and no TRAEs that led to study discontinuation^[575]^[576]^[678]^[574].

Pooled data

Pooled data from phase I/II and phase Ib trial, demonstrated no dose limiting toxicities (DLTs) in any DLT-evaluable pts with breast cancer. No deaths on study or cases of interstitial lung disease/pneumonitis were reported^[145]^[144]^[159].

Ovarian cancer

Phase III:

Updated data from the phase III DUO-O trial showed that safety was generally consistent with the known profiles of each agent. During the study, any serious adverse events were reported in 34%, 43% and 39% of pts in Arms 1, 2 and 3, respectively^[475]. Interim analysis from the phase III DUO-O trial showed that the safety and tolerability of these combinations was broadly consistent with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (greater than or equal to 20% of patients) for the combination of durvalumab, olaparib chemotherapy and bevacizumab were nausea (57%), anaemia (55%), neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%), constipation (30%), diarrhoea (30%), thrombocytopenia (28%), hypertension (26%), vomiting (26%), leukopenia (24%), headache (22%), abdominal pain (21%) and hypothyroidism (20%). Grade 3 or higher AEs were neutropenia (31%), anaemia (24%), leukopenia (8%), hypertension (7%) and thrombocytopenia (6%). Approximately 65% of patients treated with the combination of durvalumab, olaparib, chemotherapy and bevacizumab who experienced AEs during chemotherapy and throughout the maintenance phase remained on treatment at the time of data cut-off, compared to 80% of patients in the control arm (chemotherapy plus bevacizumab)^[473]. In the phase III DUO-O study, the safety and tolerability of the combinations olaparib, durvalumab, chemotherapy and bevacizumab was broadly consistent with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (greater than or equal to 20% of patients) for the combination of olaparib, durvalumab, chemotherapy and bevacizumab were nausea (57%), anemia (55%), neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%), constipation (30%), diarrhea (30%), thrombocytopenia (28%), hypertension (26%), vomiting (26%), leukopenia (24%), headache (22%), abdominal pain (21%) and hypothyroidism (20%). Grade 3 or higher AEs were neutropenia (31%), anemia (24%), leukopenia (8%), hypertension (7%) and thrombocytopenia (6%). Approximately 65% of patients treated with the combination of LYNPARZA, IMFINZI, chemotherapy and bevacizumab who experienced AEs during chemotherapy and throughout the maintenance phase remained on treatment at the time of data cut-off, compared to 80% of patients in the control arm (chemotherapy plus bevacizumab)^[474]^[472].

Phase II

In the phase II TRU-D trial, the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer showed that, skin rashes were the most common adverse events (51.1%) and grade =3 events occurred in 3 patients (15.6%), which completely resolved after steroid use^[477]^[476].

Results from a phase I/II trial in patients (n=18) with non-mucinous ovarian cancer demonstrated no dose-limiting toxicities. About 94% of the patients had an adverse event (AE). Most common AEs were anaemia (94%), neutropenia (83%), fatigue (72%), hyperglycemia (73%), and thrombocytopenia (66%). Immune-related AEs reported were included hyperthyroidism (22%), hypothyroidism (22%), diarrhea (6%), hypophysitis (6%)^[486]^[487].

Results from the phase Ib INEOV neoadjuvant trial showed that the combination of durvalumab (D) +/- tremelimumab (T) with neoadjuvant carboplatin and paclitaxel (NACP) was safe. Treatment was well tolerated, 41% of patients experienced at least one G3/4 adverse event (AE), mostly haematological attributable to NACP. There were only 6% G3/4 immune related AEs (3% vs 9% in arm A vs B), one case each: increased lipase, increased amylase, diabetes and diarrhoea. The results were obtained from 66 patients with stage IIIC/IV ovarian cancer randomised to C1 of NACP alone (immune microenvironment priming) followed by NACP + D (1125mg) at C2&C3 without (arm A) or with T (75mg) at C2 (arm B) ^[482] ^[481].

Mesothelioma

Results from the phase II trial in patients with mesothelioma receiving durvalumab in combination with pemetrexed/cisplatin demonstrated no dose limiting toxicities during the run-in period. As of January 2020 the median follow up is 20.6 months and 29 deaths have occurred^[316]^[315].

Results from phase II DUTRENEO trial showed grade 3 and 4 toxicities that were more frequent in the cisplatin-based neoadjuvant chemotherapy arms with 10 patients (62.5%) and 8 patients (36.4%) (cold) compared to 5 patients (21.7%) in durvalumab plus tremelimumab treatment^[88]^[89].

Liver cancer

In the phase II Study 22 trial, there were Grade 3/4 treatment related adverse events (trAEs) of 35.1 % reported in the tremelimumab (T)300+durvalumab (D) arm and 24.4% in the T75+D arm. Serious trAEs also occurred in the these arms with 13.5 and 11.0% respectively.There was one grade 5 trAEs occurred in the T75+D arm and 3 in the durvalumab arm. Disconituantion due to trAEs were 10.8%, 6.1%, 7.9 and 11.6% in the T300+D arm, T75+D arm as compared to durvalumab and tremelimumab alone^[287]^[289].

Gastrointestinal cancer

Results from the phase I CAMILLA trial showed that the median number of prior chemotherapies was 3 (range 1-3). Three patients were not evaluable for DLT due to missing ≥30% of DLT window doses, not related to DLT. No DLTs were observed. Drug-related Grade (G) 1&2 AEs included fatigue (83%), abnormal LFTs (39%), anorexia (26%), diarrhea (26%), nausea (13%), & hand foot syndrome (13%). One patient each developed drug related G3 hypertension, hyperthyroidism, thrombocytopenia, & thromboembolic event, all occurring outside the DLT window. The trial is conduced in 30 patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies^[636]^[635].

Biliary tract cancer (BTC):

Phase III

Results from phase III TOPAZ-1 trial demonstrated that D + GC was tolerable ^[120]. Updated Results from the phase III TOPAZ-1 trial showed Imfinzi combination reduced risk of death by 24% vs. chemotherapy alone. However, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Updated results from TOPAZ-1 after an additional 6.5 months of follow-up showed a 24% reduction in the risk of death versus chemotherapy alone (HR 0.76; 95% CI, 0.64-0.91), with more than two times as many patients treated with Imfinzi plus chemotherapy estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%). Updated median overall survival (OS) was 12.9 months versus 11.3 with chemotherapy^[103]. Updated Results from the phase III TOPAZ-1 trial showed manageable safety profile with longer follow up. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 60.9% of pts receiving D and 63.5% of pts receiving PBO; TRAEs leading to discontinuation of any study medication occurred in 8.9% and 11.4% of pts, respectively^[118]. Results from the phase III TOPAZ-1 trial, most imAEs (AEs of special/possible interest, linked to drug exposure, likely immune-mediated mechanism, no clear alternate aetiology) were manageable and grade 1/2; imAEs did not increase discontinuation. Median time to onset (mTTO) varied. imAEs occurred at any time during/after treatment. imAEs occurred in more patients in durvalumab plus chemotherapy (1 patient may have >1 imAE). Incidence of grade 3/4 or serious imAEs was low. The most common imAEs (>1% of patients in either arm) were hypothyroid events, dermatitis/rash, hepatic events and adrenal insufficiency^[117]. Previously updated results from the trial, demonstrated that the safety profile of durvalumab plus chemotherapy continued to be well-tolerated, with no new safety signals observed with longer follow-up. Grade 3 or 4 treatment-related AEs were experienced by 60.9% of patients treated with durvalumab and chemotherapy, and by 63.5% of patients receiving chemotherapy alone. Durvalumab plus chemotherapy did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone (8.9% for the durvalumab combination versus 11.4% for chemotherapy)^[116]. Updated results from the trial, demonstrated that durvalumab plus chemotherapy did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone. Grade 3 or 4 treatment-related AEs were experienced by 62.7% of patients treated with durvalumab and chemotherapy, and by 64.9% of patients receiving chemotherapy alone. The incidence of grade 3 or 4 adverse events and treatment-related adverse events were generally comparable among treatment groups, irrespective of primary tumour locations. Treatment-related AEs led to discontinuation in 8.9% of patients treated with the durvalumab combination versus 11.4% of patients receiving chemotherapy. The most common adverse reactions (≥20%) occurring in patients were abdominal pain, constipation, decreased appetite, fatigue, nausea, pyrexia and rash^[106]^[113]^[110]^[114]^[104]^[276].

Phase II

In the phase II trial of tremelimumab and durvalumab, 63.1% patients had ≥1 grade 3-4 adverse event (AE) and 21.4% had ≥1 grade 3-4 treatment-related AE (TRAE). The most commonly reported G3-4 AEs were fatigue, abdominal pain and aspartate aminotransferase increase and grade 3-4 TRAEs were fatigue and diarrhea^[124]^[123].

Phase I

In a phase I trial in patients with BTC demonstrated that nausea, vomiting (8.4 [4.45 to 12.36]), dyspnea (7.28 [2.17 to 12.4]), constipation (9.24 [3.35 to 15.13]), financial difficulties (5.53 [1.65 to 9.41]) in C30 and eating (5.53 [1.65 to 9.41]), tiredness (5.42 [1.23 to 9.6]), treatment side effects (7.98 [1.15 to 14.81] in BIL21 were worse at post 2 cycles. However, pain (-7.14 [-12.24 to -2.04]), diarrhea (-4.48 [-8.86 to -0.1]) in C30 and jaundice (-5.51 [-9.26 to -1.76]), pain (-6.02 [-9.7 to -2.34] in BIL21 were improved and more improvement was shown in responder compared to non-responder. The most common adverse events (AEs, any grade) were neutropenia (54.5%), nausea (59.5%), and pruritus (55.44%). The most common grade 3/4 AEs were neutropenia (50.4%), anemia (35.5%), and thrombocytopenia (16.5%)^[127]^[126]^[125]

Non-small cell lung cancer

In a phase II trial, treatment with durvalumab was safe in patients with non-small cell lung cancer. Disease progression resulted in death of thirteen patients as the most frequent reason (11 patients). Grade 3 adverse event was reported in 59 patients (88.1%) which included postoperative bleeding complication and respiratory failure^[433]^[432].

In the phase II NeoCOAST trial, treatment with neoadjuvant durvalumab alone or in combination with oleclumab, monalizumab or danvatirsen, for the treatment of patients with non-small cell lung cancer demonstrated that, rates of treatment-related AEs were 34.6% with durvalumab, 57.1% with durvalumab plus oleclumab, 50.0% with durvalumab plus monalizumab , and 43.8% with durvalumab plus danvatirsen (grade =3 in 0%, 4.8%, 0% and 6.3%, respectively). Most patients (76/83; 91.6%) completed surgery with no significant delay; of the 7 patients unable to, 5 had progressive or stage IV disease^[425]^[424].

Treatment with tremelimumab and durvalumab with stereotactic body radiotherapy (SBRT), was safe and generally well tolerated, in patients (n=17) with oligometastatic non-small cell lung cancer, in a phase Ib trial. DLTs were seen in 2/17 (11.8%) patients; DLTs were autoimmune hepatitis and autoimmune pancreatitis. Most treatment-related adverse events (TRAEs) were grade (G) 1/2. TRAEs included: all TRAEs n = 188, 88.2% (of patients); G 3 n = 17, 29.4%; G 4 n = 1, 5.8%. There were no treatment-related deaths. Five patients discontinued treatment due to grade 3/4 immune related adverse events (IRAE). Six of 17 (35.2%) patients experienced disease progression and 4/17 (23.5%) patients died of disease progression^[450]^[451].

Solid tumours:

In Part A of the phase I CLOVER trial, durvalumab in combination with chemoradiation, was generally well tolerated in patients with locally advanced HNSCC, unresectable, stage III NSCLC, and LS-SCLC. Adverse events (AEs) were reported in 8/8 (100%) patients in HNSCC cohort (n=8), 6/6 in arm 1, 7/7 in arm 2 and 6/6 patients in arm 3 in NSCLC cohort (n=19), and 7/7 in arm 1 and 6/6 in arm 2 in LS-SCLC (n=13) cohort. Grade 3/4 (AEs) were reported in 7/8 patients in HNSCC cohort, 5/6 in arm 1, 7/7 in arm 2 and 4/6 patients in arm 3 in NSCLC cohort, and 7/7 in arm 1 and 6/6 in arm 2 in LS-SCLC cohort. Serious AEs were reported in 2/8 patients in HNSCC cohort, 5/6 in arm 1, 5/7 in arm 2 and 1/6 patients in arm 3 in NSCLC cohort, and 1/7 in arm 1 and 1/6 in arm 2 in LS-SCLC cohort. AEs leading to treatment discontinuation were reported in 2/8 patients in HNSCC cohort, 2/6 in arm 1, 2/7 in arm 2 and 1/6 patients in arm 3 in NSCLC cohort, and 1/7 in arm 1 and 0/6 in arm 2 in LS-SCLC cohort. Immune-related AEs were reported in 3/8 patients in HNSCC cohort, 3/6 in arm 1, 5/7 in arm 2 and 3/6 patients in arm 3 in NSCLC cohort, and 4/7 in arm 1 and 2/6 in arm 2 in LS-SCLC cohort. Stomatitis, lymphopenia, leukopenia and elevated amylase were most common grade 3/4 AEs reported in the HNSCC cohort. In the NSCLC and LS-SCLC cohorts, neutropenia, leukopenia and anaemia were most common grade 3/4 AEs reported. The high rate of grade 3/4 AEs was similar to historical data of CRT used as backbone therapy in these indications. A dose-limiting grade 3/4 transaminitis was reported in one patient in the NSCLC cohort in arm 1. One patient died due to acute kidney injury in the HNSCC cohort, whereas total three patients died in the NSCLC cohort due to pneumocystis jirovecii pneumonia (arm 1), acute coronary syndrome (arm 2) and cardiac arrest (arm 3). Eight patients were treated with durvalumab + chemorediotherapy in the HNSCC cohort, 19 in the NSCLC cohort, and 13 in the LS-SCLC cohort. In whole trial,patients were randomised in three cohorts: HNSCC: durvalumab + cisplatin + radiotherapy (RT); NSCLC: durvalumab + cisplatin + etoposide (EP) + RT (arm 1); durvalumab + carboplatin + paclitaxel + RT (arm 2); or durvalumab + pemetrexed + carboplatin or cisplatin + RT (arm 3); LS-SCLC: durvalumab + etoposide + RT (arm 1); durvalumab + etoposide + hyperfractionated RT (arm 2); durvalumab + tremelimumab + etoposide + RT (arm 3); or durvalumab + tremelimumab+ etoposide + hyperfractionated RT (arm 4)^[597]^[596].

In a phase II trial, durvalumab and tremelimumab treatment was well tolerated in patients with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origin. Most common TRAEs included fatigue (43%), diarrhoea (31.7%), pruritus (23.6%), nausea (13.8%), and hypothyroidism (9.8%). Most frequent grade ≥3 TRAEs include liver toxicity (9.7%), diarrhoea (6.5%), fatigue and vomiting (2.4% each)^[644]^[643].

Updated results from the phase Ib/II trial demonstrated 25 patients were treated in part 1, dose-limiting toxicities occurred in 1 pt (Cohort B, O 3000 mg: Gr 3 nausea and Gr 3 localized edema). Safety was generally similar in parts 1 and 2. In part 2, Gr ≥3 treatment-emergent adverse events (TEAEs) occurred in 85.5%, 89.5% and 90.0% of pts in Arms A1, A2 and A3 respectively, most commonly neutropenia (22.6%, 34.2% and 17.1%). In Part 2, TEAEs led to discontinuation in 11.3%, 23.7% and 24.3% of pts respectively ^[493] In a phase Ib/II trial conducted in renal cancer, guadecitabine plus durvalumab treatment was well tolerated. With durvalumab, dose limiting toxicity of neutropenia was seen at 60 mg/m². The dose level -1 of guadecitabine at 45 mg/m² subcutaneously for 5 days starting day 1 of a 28-day cycle plus durvalumab 1500 mg IV on day 8 was determined as safe dose for phase II evaluation. With guadecitabine treatment, incidence of treatment related adverse events (TRAE) of any grade was 24.4%, it was 20.1% with durvalumab, and it was 35.4% with either guadecitabine and durvalumab. The most common grade 3 AE was neutropenia. The other grade 3 AEs noted in one patient each were abdominal pain, diarrheoa, dyspnea and pneumonitis. There were no treatment related deaths. One patient discontinued the study due to pneumonitis^[517]^[516].

Interim results of the phase II CALIBRATION trial showed that durvalumab well tolerated in patients (n = 6) with advanced oesophageal adenocarcinoma. The adverse events (AE) observed were 68% Grade 1-2, 32% (8/25) Grade 3, but none were drug-related. Two drug-related AEs included hyperamylasemia and hypothyroidism, which led to dose delay and withdrawal, respectively. Both AEs were resolved^[464]^[463].

In the phase Ib portion of the phase Ib/II DEDUCTIVE trial in hepatocellular carcinoma, tivozanib and durvalumab combination was well tolerated, with no dose-limiting toxicities. The phase Ib portion enrolled seven patients^[279]^[281].

Updated results from a phase I trial in solid tumour patients (n=61) showed that there were no dose-limiting toxicities for MEDI 1191 and no maximum tolerated dose was identified. Gr ≥3 MEDI 1191-related adverse events (AEs) occurred in 3 patients (4.9%; Gr 3 asthenia and pyrexia, each n=1; Gr 4 lymphocyte count decreased, n=1); 2 patients (3.3%) had a MEDI 1191-related serious adverse event (SAE; Gr 2 pyrexia and confusion, each n=1). Gr ≥3 D-related AEs occurred in 3 patients (4.9%; Gr 3 asthenia, pyrexia [both also MEDI1191-related] and pruritus; each n=1); 1 patients (1.6%) had a D- and MEDI 1191-related serious adverse event (Gr 2 pyrexia)^[60]. Earlier results show that sequential combination of intratumoural MEDI 119 with intravenous durvalumab treatment was well tolerated. Only two partial responses were reported, both of which had received immuno-oncology (IO) therapies and had PD-L1 negative tumours, including one with melanoma with tumour shrinkage of both injected and non-injected lesions following two doses of MEDI 1191 prior to durvalumab. The data was obtained from 10 patients enroled across three dose escalation cohorts in part 1 of trial ^[59]^[57].

Results from a phase I trial in patients with solid tumours and CNS cancer demonstrated that of the 14 patients evaluable for dose limiting toxicity (DLT), 3 were on DL1 and 11 on DL2. Only 1 DLT was observed, Grade 3 intracranial hemorrhage (ICH). There were no treatment related deaths. There were 72 treatment-related adverse events (TRAEs) observed in 11 patients in a total of 73 cycles administered on the trial. The most common TRAE was AST elevation (7 instances in 4 patients). All TRAEs were < grade 3 except for 1 instance each of grade 3 AST elevation, anemia, and ICH^[602]^[600].

Muscle invasive bladder cancer

In phase II IMMUNOPRESERVE study, durvalumab and tremelimumab combination was safe in patients with bladder cancer. Adverse events due to radiotherapy and/or immunotherapy were observed in 31 (97%) patients. Most frequent adverse events were diarrhea (41%) and urinary disorders (37.5%). Treatment related grade 3 or 4 adverse events were observed in 31% patients which included gastrointestinal toxicity (12.5%), acute kidney failure (6%) and hepatitis (6%) as the most frequent^[92]^[91].

In updated results from a phase II trial that evaluated safety and efficacy of olaparib in combination of durvalumab, the combination was well tolerated (n=10). In a median duration of treatment 1.95 months (range 1.8-13.5) there were no treatment-related grade 3-4 toxicities. Any grade toxicities included fatigue (100%), nausea (60%), anemia (20%), hypothyroidism (20%), elevated liver enzymes (20%)^[547]. Earlier results from the trial showed that combination of olaparib and durvalumab was well tolerated in glioma patients (n=9). Common treatment emergent adverse events were all grade 1: fatigue (8 patients), nausea (6), abdominal pain (3), anaemia (3), thrombocytopenia (3), and diarrhoea (2)^[545]^[546].

Results from phase II COAST trial showed grade 3 or higher treatment-emergent adverse events, they were 39.4% with durvalumab, 40.7% with durvalumab plus oleclumab, and 27.9% with durvalumab plus monalizumab. The most common grade 3/4 TEAE was dyspnoea (reported 3.0% with durvalumab, 1.7% with durvalumab plus oleclumab and 1.6% with durvalumab plus monalizumab patients). Grade 3/4 pneumonitis was only reported for one patient (1.6%), who received durvalumab plus monalizumab. Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% with durvalumab+oleclumab and 21.3% with durvalumab+monalizumab, with grade ≥3 events in 3.0%, 3.4% and 1.6%^[675]^[372]^[373]^[371]

Hepatocellular carcinoma

Updated results from the phase III HIMALAYA trial at four years of follow-up showed that the safety profiles of the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen and for Imfinzi (durvalumab) alone were consistent with the known profiles of each medicine, and no new safety signals were identified. Serious treatment-related adverse events (TRAEs), defined as Grade 3 or 4 and including death, were experienced by 17.5% of patients treated with the STRIDE regimen versus 9.6% of patients treated with sorafenib, with no new events occurring after the primary analysis for STRIDE (17.5%)^[277]. Previous results showed that Grade 3 or 4 treatment-related adverse events (AEs) were experienced by 25.8% of patients treated with the STRIDE regimen and by 12.9% of patients treated with Imfinzi alone, versus 36.9% of patients on sorafenib. Incidence of Grade 3 or 4 treatment-related hepatic events were low across treatment arms (5.9% for the STRIDE regimen and 5.2% for Imfinzi, versus 4.5% for sorafenib). Treatment-related AEs led to treatment discontinuation in 8.2% of patients treated with the STRIDE regimen and 4.1% of patients treated with Imfinzi alone, versus 11% for sorafenib^[273]^[114]^[272].

In a phase II trial, durvalumab demonstrated a favorable safety profile in BCG-unresponsive patients (n = 17) with urothelial carcinomatrial. Grade 1-2 treatment-related adverse events occurred in 11 patients. Most frequently fatigue (35%), diarrheoa (18%), pancreatic enzyme elevation (12%), rash (6%), and hypothyroidism (6%)^[95]^[96].

Results from phase II trial in patients with hepatocellular Carcinoma (HCC) or biliary Tract Carcinomas (BTC) demonstrated that was well Combined checkpoint inhibitors (ICI) with Durva/ Treme with and without radio frequency ablations (RFA) is well tolerated. The most common study hematologic related Grade 3-4 adverse events (AEs) were lymphopenia (n=6) and anemia (n=3) and the most common non hematologic AEs included increased AST (n=9), increased alk phos (n=7) and increased total bilirubin (n=6) ^[295]^[294].

The adverse events data from phase Ib trial durvalumab in combination with tremelimumab in liver cancer showed safety of STRIDE (Single tremelimumab regular interval durvalumab) in combination with particle therapy in HCC (hepatocellular carcinoma) participants with MVI (macrovascular invasion). The trial was designed in two cohorts, where cohort A enrolled 3 HCC participants with macrovascular invasion (MVI) and cohort B enrolled 12 participants with Single tremelimumab regular interval durvalumab (STRIDE). Cohort A showed no adverse events and 4 participants in cohort B (26.7%) experienced serious treatment-related adverse events^[296]^[297]

Non-small cell lung cancer

Updated positive results from the phase III AEGEAN trial showed that durvalumab was generally well tolerated and no new safety signals were observed in the neoadjuvant and adjuvant settings. During the post-surgery period, 40.2% and 39.2% of durvalumab- and placebo-treated modified intent-to-treat (mITT) patients, who underwent surgery, had any AEs possibly related to surgery; 8.4% and 9.3% had maximum grade 3/4 AEs possibly related to surgery. Surgical complications occurred with similar frequency (59.3% vs 59.9% of mITT patients who had surgery) were maximum grade 1/2 (53.2% vs 51.7%)^[380]. Further, adding IMFINZI to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients' ability to complete surgery versus chemotherapy alone. Of patients treated with the IMFINZI-based regimen, 77.6% completed surgery compared to 76.7% of patients treated with chemotherapy alone. Grade 3/4 any-cause adverse events occurred in 42.3% of patients treated with the IMFINZI-based regimen versus 43.4% for chemotherapy alone^[379]. Earlier treatment with durvalumab in patients with resectable non-small cell lung cancer in a phase III AEGEAN trial was safe and generally well tolerated and no new safety concerns were observed in the neoadjuvant and adjuvant settings. Durvalumab to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not increase complications or adverse events, or compromise patient's ability to undergo surgery versus chemotherapy alone^[378]. Earlier results showed that the safety profile of durvalumab was consistent with the known profile for this combination and did not decrease the number of patients able to undergo successful surgery versus chemotherapy alone ^[377]^[376]

Data from phase-II DURATION trial showed rate of grade III/IV adverse events 34%, 34%, 24% and 29% for sequential doublet-chemotherapy (dCTX) , sequential doublet-chemotherapy followed by durvalumab (dCTX-D), mono-chemotherapy with durvalumab (mCTX-D and mCTX respectively (p=0.68). Treatment-related deaths were reported in 1% (n=2, dCTX-D and mCTX^[429]^[672]

Phase II

In a phase II trial, durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (nwith unresectable stage III non-small cell lung cancer (NSCLC) maintained a similar safety profile to that seen with durva after cCRT in PACIFIC. Overall, 4.3% (95% CI: 1.4–9.7) of patients had grade 3/4 PRAEs within 6 month, and 6.0% had grade 3/4 PRAEs during the entire study period (1 patient had a PRAE with outcome of death). Pneumonitis was the most frequently reported PRAE of any grade (17.1%) and grade 3/4 (1.7%). 27.4% of patients discontinued durva due to AEs of any cause. Median duration of follow-up among patients censored for OS was 32.6 mo (range: 4.4–45.7). Median OS was 39.0 mo (95% CI: 30.6–not calculable), the 3-yr OS rate was 56.5% (95% CI: 46.4–65.5), and median PFS was 13.1 mo (95% CI: 7.4–19.9)^[354]^[353].

Phase I

Data from the phase I trial deomonstrated that the combination of JCAR 014 with durvalumab for the treatment of adult patients with large B-cell lymphoma was safe.The most common adverse events observed of any grade related to lymphodepletion (LD) and JCAR 014 with or without durvalumab were cytokine release syndrome (CRS) (41%), neutropenia (21%), neurotoxicity (17%), and hypogammaglobulinemia (17%). The incidences of any grade and grade ≥ 3 CRS and neurotoxicity were similar between cohorts. Patients in cohort 2 had later onset of CRS after JCAR 014 infusion compared with cohort 1 (median of 6 vs. 4 days, P = .05) and shorter duration of CRS (median of 3 vs. 8 days, P = .08). Among the 27 patients evaluated for dose-limiting toxicity (DLT), 2 (7%) had DLT of which 1 patient with grade 4 CRS (durvalumab 250 mg) and 1 patient with prolonged grade 3 neurotoxicity (durvalumab 750 mg) in cohort 2 was observed. No maximum-tolerated dose of durvalumab was identified.The open-label, non-randomised trial enrolled 29 patients^[461]^[676]

Results from phase I trial in solid tumours showed twenty-nine (29) Grade 3-4 toxicities in 13 patients^[449]^[447].

Gastric cancer

Phase III

Liver cancer

The updated results from the phase III EMERALD-1 trial in patients with Hepatocellular carcinoma demonstrated that in the analysis sets for patients treated with Durvalumab (D) in combination with trans-arterial chemoembolization (TACE) and bevacizumab (B) (D+B+TACE) (n=154), D+TACE alone (n=232), and TACE alone (n=200), a respective 32.5%, 15.1%, and 13.5% experienced maximum Grade 3/4 treatment-related adverse events (TRAEs). Additionally, 8.4%, 4.3%, and 3.5% discontinued treatment due to TRAEs, and there were no TRAE-related deaths in the D+B+TACE group, while 1.3% and 2.0% died in the D+TACE and TACE groups, respectively. Patients are currently being monitored for overall survival (OS)^[286]. Previous safety data from the phase III EMERALD-1 study showed that the Durvalumab in combination with trans-arterial chemoembolization (TACE) and bevacizumab was well tolerated with no serious treatment emergent adverse events observed. The safety profiles for the drugs were consistent with the known profile of each medicine, and there were no new safety findings. The number of TACE procedures was consistent across arms. No new safety signals were observed. Grade 3 and 4 adverse events due to any cause occurred in 45.5% of patients treated with IMFINZI plus TACE and bevacizumab and 23% of patients treated with TACE alone ^[285]^[284]^[283].

Results from the phase III PACIFIC-2 trial in demonstrated that the profiles were broadly consistent with the known profiles of these treatments, although there was an increased rate of infection observed during the concurrent treatment period in the experimental arm^[384]^[383].

Cutaneous T-cell lymphoma

Phase I/II

Results from a phase I/II trial, combination treatment with durvalumab/lenalidomide was well tolerated. The data reported one patient died one month after discontinuation from study due to PD. No serious AEs were observed. The most common treatment-emergent adverse events (shown below for combo arm) were more frequent in the durvalumab/lenalidomide arm vs durvalumab arm and included fatigue (n=9), diarrhea (n=4), decreased platelets (n=4), leg edema (n=3), constipation (n=3), hyperglycemia (n=3), anemia (n=3), and leukopenia & neutropenia (n=3). The majority of AEs with both treatment arms were mild to moderate in severity (grade I/II, 91%; grade III, 8 %). No grade IV event except 1 neutropenia on combo arm was observed^[653]^[652].

Pharmacodynamics

Summary

Hepatocellular carcinoma

Phase II: In the phase II Study 22 trial, treatment with tremelimumab [see Adis Insight drug profile 800020650] in combination with durvalumab, in patients (n=332) with hepatocellular carcinoma demonstrated that there were no significant differences in baseline T-cell clonality as assessed by immunosequencing analysis. Increased T-cell clonal expansion appeared to be T dose dependent with no significant difference observed in the median expansion between the D and T75+D arms at day 29. Larger median number of expanded T-cell clones were observed in responders as compared to non-responders (77.5 vs 40) at day 29 accompanied with longer overall survival (OS) across all-arms. Further evaluation by arm demonstrated an increase in T-cell clonal expansion in responders vs nonresponders in the T300+D arm. Patients with T-cell expansion above the median in the T300+D and T75+D arms also exhibited longer OS. Both newly expanded and total expanded clones on Day 29 vs Day 1 were associated with improved OS^[290]^[289]

Dose-dependent suppression of soluble PD-L1 was observed after treatment with durvalumab in patients with advanced solid tumours in a phase I trial (Study 1108)^[591].

Durvalumab suppressed B7-H1 mediated suppression of T-cell activation and enhanced sub-optimal T-cell activation during in vitro studies. Furthermore, durvalumab did not trigger cytokine release in whole blood and was only able to activate T-cells in the presence of an active T-cell receptor signal. In vivo activity was also recorded during a xenograph study with antitumor activity dependent on tumour specific human T-cells^[679].

Combination of NKG2A and PD-1 checkpoint inhibitors exhibited significantly enhanced anti-tumour responses, whereas monotherapy with these agents showed modest anti-tumour efficacy in an in vivo murine model of PD-L1 expressing solid tumours. With the combination therapy, approximately twice as many mice achieved complete tumour cell regression compared with anti-PD-1 treatment alone. In mice studies, blockage of both NKG2A/HLA-E and PD-1/PD-L1 pathways enhanced anti-tumour responses of NK and CD8+ T cells in vitro and in vivo. This data supports combination of monalizumab with durvalumab for treatment of solid tumours^[452]^[671].

Interim results of the phase II CALIBRATION trial in patients (n = 6) with advanced oesophageal malignancies receiving durvalumab showed a relationship between changes in ctDNA and RECIST response. The individual gene changes reflect RECIST responses, Third patient had partial response (PR) & ≥10% relative reduction in tumour-derived variant allele fractions (VAFs, like PI3KCA, TP53, APC, ERBB2) and copy-number alterations (CN, like CDK4, FGFR2, CCNE1). Second patient had PD and ≥10% relative increase of VAFs (TP53, BRCA1, ATM) and CN (KRAS, EGRF)^[464]^[463].

Phase I/II

Results from a phase I/II trial in patients (n=18) with non-mucinous ovarian cancer demonstrated that the identification of 13 significantly differentially expressed proteins among 211 proteins (adj. p<0.1, log2FC≥1). One upregulated protein, XBP1 (log2FC=1.37) and 12 downregulated proteins were observed, including EMA, PAR, IGFBP2, and EVI1, at post- compared to pre-treatment. PD-L1 expression was significantly elevated post-treatment (adj. p=0.0065). Pathway analysis revealed pyruvate metabolism and citric acid (TCA) and PI3K/AKT were also upregulated in post- compared to pre-treatment (p<0.05, FDR<1). Cell cycle, mismatch repair, DNA double-strand break ends processing, and homology-directed repair (HDR) through homologous recombination were downregulated in post- compared to pre-treatment samples (p<0.05, FDR<0.5).^[486]^[487]

Exploratory analysis results of the open-label phase III CASPIAN trial in patients with extensive stage small-cell lung cancer (ES-SCLC) observed that the Inflamed or YAP1 subtype showed the longest overall survival (OS) in the durvalumab (D) plus platinum-etoposide (EP) arm, among the four SCLC molecular subtypes. About 57/268 (21.3%) patients in the D+EP arm and 47/269 (17.5%) patients in the EP arm had RNA sequencing data (biomarker-evaluable population; BEP). In the BEP, the percentage of patients with WHO PS 1 was slightly higher and the percentage with brain metastases slightly lower at baseline vs the ITT population. In the BEP, median OS (mOS) was 11.8 months in the D+EP arm vs 9.1 months in the EP arm (HR 0.61; 95% CI: 0.40, 0.92). Prevalence of neuroendocrine (ASCL1 and NEUROD1) and non-neuroendocrine subtypes (POU2F3 and YAP1 [Rudin] or Inflamed [Gay]) was similar using both methods. However, ASCL1 was more prevalent and NEUROD1 less prevalent with the Rudin method. Inflamed and YAP1 subtypes (11% and 8% prevalence) showed high concordance between methods. Using either method, the median OS in the D+EP arm was higher in the Inflamed or YAP1 subtype vs the other three subtypes^[535]^[533].

Pooled results from 1108, CONDOR, HAWK and EAGLE trials in 467 patients with head and neck squamous cell carcinoma showed the prognostic value of inflammation, disease burden, tumour angiogenesis, and immunomodulatory factors on the clinical outcomes of patients treated with durvalumab. The final tumour model highlighted that high tumor burden, elevated LDH and neutrophil-lymphocyte ratio were associated with faster tumour growth while patients with lower baseline tumour burden had an increase in net tumour shrinkage. For overall survival, the tumour size-driven hazard model suggested that high levels of immunomodulators (IL23, Osteocalcin), low inflammation (IL6, NLR), low tumour burden, and low angiogenesis factors [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1)] were associated with survival benefits for patients treated with durvalumab. Specifically, these patients had baseline serum IL23 > 2.1 pg/mL and Osteocalcin > 32 pg/mL or serum PAI-1 < 229 pg/mL and serum IL6 < 5.4 pg/mL which corresponded to a hazard ratio estimate (HR and 95%CI) of 0.36 (0.27- 0.47), log rank p-value: 2.3x10⁻¹⁴. The median (n, 95%CI) overall survival time for the patients with favorable biomarker profile was 14.6 months (n = 129, 11.2-21.4) vs. 4.4 months (n = 217, 3.6-5.3)^[219]^[220]^[221]^[222]^[218].

Results of the open-label phase II trial of adjuvant durvalumab following trimodality therapy in patients (n = 37) with locally advanced oesophageal (LA-EAC) cancer and GEJ adenocarcinoma showed that mutations in DNA repair genes were prevalent in patients with delayed relapse. Mutations in DNA repair genes (ARID1A, ATM, ATR, CHEK2), and PIK3CA E542K were more prevalent among late relapsing patients. Circulating tumour cells (CTCs) analysis from 10/37 patients, showed that in 4/5 patients CTCs increased from C1 to C4 had disease relapse. Mutations in DNA repair genes (ARID1A, ATM, ATR, CHEK2), and PIK3CA E542K were more prevalent among late relapsing patients^[466]^[465].

Pooled results from two phase II CONDOR and HAWK trials of durvalumab (D) ± tremelimumab (T) in patients (n = 153) with head and neck squamous cell carcinoma demonstrated that tumour mutation burden (TMB) is a possible predictive biomarker of IO HNSCC therapy. patients (n = 153) had paired evaluable FFPE tumour and PBMC samples (HAWK, n = 48; CONDOR, n = 105). TMB distributions were similar between studies (P = 0.43). TMB correlated with smoking (P = 0.02) but not HPV (P = 0.24), NLR (P = 0.66), or PD-L1 status (P = 0.43). Overall, high TMB (≥upper tertile) trended with longer OS versus low TMB in all evaluable patients [N = 153; 9 versus 5.6 m; HR = 0.70; 95% CI: 0.48-1.01); P = 0.06]. In HAWK study, there was no association of TMB with OS. In CONDOR, patients (D and D+T arms) with high TMB versus low had significantly longer OS (N = 76; 16.3 versus 5.3 month; HR = 0.53; 95% CI = 0.31-0.92). TMB and OS association was further assessed by increasing TMB cutoffs. Improved HRs trended with higher cutoffs; cutoffs ≥upper quartile significantly linked to OS. TMB was not associated with PFS or ORR. Patients with low PD-L1 and low TMB had worse OS compared to patients with high PD-L1 or high TMB. Patients with high NLR (≥median) and low TMB had significantly worse OS than patients with low NLR and high TMB (HR = 2.63, P< 0.001). Analysis of germline HLA alleles revealed significantly poorer survival for carriers of the HLA-B*15:01 allele (9.4%) (HLA-B variant status did not affect TMB and OS association in CONDOR). Germline HLA heterozygosity did not impact OS. Patients with mutations in ATM (5%), a DNA damage repair gene, also trended with prolonged OS^[239]^[221]^[222].

In the phase II Study 22 trial treatment with durvalumab demonstrated a unique proliferative T cell profile for patients in the T300+D arm suggesting additive biologic activity for the combination. The T cell profile showed patients with an OR exhibited high cytotoxic (CD8) counts^[287]^[289]

Results from a phase I trial in solid tumour patients (n=61) showed that MEDI 1191 induced pharmacodynamic changes in the periphery and tumor microenvironment. A ≥2-fold increase in serum IL-12 levels was seen in 42/46 pts, with increases in serum IFNγ in 37/46; 9/22 pts had ≥2-fold increases in CD8+ T cell tumor infiltration and tumoral PD-L1 expression^[60]^[57].

Immunogenicity

Summary

In a phase I/II study, treatment with durvalumab in combination MEDI 0680 in patients with cancer, increased Ki67+ (proliferating) CD4+ and CD8+ T cells. Treatment also resulted in elevatvation of circulating IFN-γ, CXCL 9, CXCL 10, and CXCL11 levels, which indicated pharmacodynamic activity of PD-1/PD-L1 pathway blockade. Results were reported from 30 patients enrolled in an open-label study^[617]^[616].

Data from the phase Ib/II SCORES trial indicated that second line therapy with durvalumab, in combination with danvatirsen (AZD 9150) [see Adis Insight Drug Profile 800021483], demonstrated drug uptake in immune cells and fibroblasts, along with reduction in a suppressive cell gene expression signature (GES), and increase in an IFNy GES^[249]^[246].

Small cell lung carcinoma:

Phase II:

In the phase II trial, treatment with durvalumab in combination with tremelimumab, increased circulating CD8(+) lymphocytes on treatment versus baseline in patients with objective tumour response^[541]^[542].

Breast cancer:

Phase I:

Treatment with PVX 410 with durvalumab (DUR) in a phase Ib trial for breast cancer showed that comparing baseline to week 14, 10 of 12 patients demonstrated a PVX specific immune response. Immune response persisted in all patient samples tested at 6 months. Most patients had increases over baseline in the proportions of CD3+CD8+ T cells that expressed TNFα, IL-2, and CD137 following the in vitro stimulation with PVX peptides^[164]^[165].

Head and neck cancer:

Phase

II: Immunophenotyping results from phase II CheckRad-CD8 trial revealed that in treatment with combination of cisplatin/ docetaxel plus durvalumab/ tremelimumab, a trend of slight reduction of CD8+ T-cells in the peripheral blood of patients with initially lower numbers of intratumoral CD8+ T-cells. The early activation marker CD69 is increased on T-cells and PD-1 on T-helper cells after induction treatment^[226]^[225].

Therapeutic Trials

Phase III

The updated results from the phase III EMERALD-1 trial in patients with Hepatocellular carcinoma demonstrated that the demographic and baseline characteristics were generally balanced across arms. 616 patients were randomised to receive Durvalumab (D), in combination with trans-arterial chemoembolization (TACE) and bevacizumab (B) (n=204), D+TACE (n=207), or TACE (n=205). At final PFS analysis, the primary objective was met: PFS significantly improved for D+B+TACE vs TACE (median [m]PFS 15.0 vs 8.2 months [mo]; hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98; p=0.032 [threshold 0.0434]). The secondary endpoint of PFS for D+TACE vs TACE was not statistically significant (median progression free survival (mPFS) 10.0 vs 8.2 mo; HR, 0.94; 95% CI, 0.75–1.19; p=0.638). ORR was 43.6%, 41.0%, and 29.6%, and mTTP was 22.0, 11.5, and 10.0 mo for D+B+TACE, D+TACE, and TACE, respectively^[286]. Previous data from the phase III EMERALD-1 trial in patients with Hepatocellular carcinoma showed that Durvalumab, in combination with trans-arterial chemoembolization (TACE) and bevacizumab demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) versus TACE alone in patients with hepatocellular carcinoma (HCC) eligible for embolization. In the trial, treatment with IMFINZI plus TACE and bevacizumab reduced the risk of disease progression or death by 23% compared to TACE alone (based on a hazard ratio [HR] of 0.77; 95% confidence interval [CI] 0.61-0.98; p=0.032 [threshold 0.0434]). The PFS benefit observed was generally consistent across key prespecified subgroups. The secondary endpoint of time to progression (TTP) further supports the clinical benefit of IMFINZI plus TACE and bevacizumab in this setting, with a median TTP of 22 months versus 10 months for TACE (HR 0.63; 95% CI 0.48-0.82). Treatment of IMFINZI plus TACE and bevacizumab (n=204) and placebo plus TACE (n=205). PFS HR (95% CI) was 0.77 (0.61-0.98). p-value was 0.032. PFS rate at 12 months (%) 55.5 and 39.8. PFS rate at 18 months (%) was 43.1 and 28.3. TTP HR (95% CI) was 0.63 (0.48-0.82). The threshold of significance for this analysis was 0.0435 based on the alpha spend at the PFS interim analysis (2.27%) and the actual number of events at PFS final analysis ^[285]^[284]^[283]

The results from the phase III EAGLE trial in patients with squamous cell carcinoma of head and neck showed that durvalumab (D) (monotherapy) (n = 240) and the combination therapy of durvalumab and tremelimumab (D+T) (n = 247) did not exhibit a statistically significant improvement in the overall survival (OS) when compared to standard chemotherapy (SOC) (n = 249). The median OS for the three arms with CI: 95 % were D [7.6 (6.1–9.8)], D+T [6.5 (5.5–8.2)] and SOC [8.3 (7.3–9.2)]. The survival rate for the three arms with CI: 95 % at 12 months were D [37.0 (30.9–43.1)], D+T [30.4 (24.7–36.3)] and SOC [30.5 (24.7–36.4)] and at 24 months D [18.4 (13.3–24.1)], D+T [13.3 (8.9–18.6)] and SOC [10.3 (5.7–16.5)]. The overall response rate for the three arms with CI: 95 % were D [17.9 (13.3–23.3)], D+T [18.2 (13.6–23.6)] and SOC [17.3 (12.8–22.6)]. The duration of response for D arm was 12.9 months; D+T was 7.4 months and SOC arm 3.7 months.An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favour of the SOC arm (D, PS 0 = 26 %, PS 1 = 74 %; D+T, PS 0 = 26 %, PS 1 = 74 %; SOC, PS 0 = 32 %, PS 1 = 68 %)^[216]^[218]

Updated 5-year data from the phase III PACIFIC trial, exhibited a durable and sustained overall survival (OS) benefit in patients with unresectable, stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. As of data cut-off (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated 4-year data the phase III PACIFIC trial, exhibited a durable and sustained overall survival (OS) benefit in patients with unresectable, stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. Approximately half of patients randomised to durvalumab in the trial were alive at 4 years, and about a third were both alive and progression free, for almost 3 years. The 48-month OS rates were 49.6% for durvalumab compared with 36.3% for placebo, and the rates of PFS rates were 35.3% and 19.5% for durvalumab and placebo, respectively. At afollow up, 34.2 months updated PFS (stratified HR 0.55, 95% CI 0.44–0.67; median 17.2 vs 5.6 months) and OS (stratified HR 0.71, 95% CI 0.57–0.88) was with previous data. Median OS for the durvalumab arm was determined for the first time 47.5 months (pbo, 29.1 months). Updated results from the trial showed durvalumab showed a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit at five years in patients. Long-term data showed 33% of patients remained progression-free at five years. Results from the updated post-hoc analyses showed an estimated five-year OS rate of 42.9% for patients treated with durvalumab versus 33.4% for those on placebo after CRT. Median OS was 47.5 months for durvalumab versus 29.1 for placebo. Following a maximum treatment course of one year, an estimated 33.1% of patients treated with durvalumab had not progressed five years after enrollment versus 19% for placebo. The OS rate was 57 % at three years for patients receiving durvalumab 43.5% for placebo following concurrent CRT. Median OS was not yet reached with the durvalumab when compared to placebo at 29.1 months. After 11.2 months, durvalumab demonstrated a statistically-significant and clinically-meaningful improvement in progression free survival (PFS) (first primary end point), as compared with placebo, in 713 patients with non-small cell lung cancer. PFS improvement was observed across all pre-specified sub-groups, including PD-L1 expression status. The patients who received durvalumab exhibited a lower incidence of metastases, as compared with those receiving placebo. The median PFS values for durvalumab and placebo (standard-of-care) were 16.8 months and 5.6 months, respectively [HR-0.52; 95% CI: 0.42-0.65, p<0.0001]. The duration of response (DoR) was not reached for durvalumab, while the corresponding value for placebo was 13.8 months. The objective response rate (ORR) showed values of 28.4% [95% CI: 24.28-32.89, p < 0.001] and 16% [95% CI: 11.31-21.59, p<0.001], for the drug and placebo, respectively. The trial also met the second primary end point of overall survival (OS) in patients receiving durvalumab compared with placebo by demonstrating 38.4% deaths in treatment arm compared to 48.9% in placebo group. In primary analysis, durvalumab reduced the risk of death by 32% (HR 0.68, [99.73% CI, 0.47-0.997], p = 0.0025).Additionally, durvalumab also showed that PFS was reached by 51.1% patients compared to 73% patients in placebo. After a year of follow up, durvalumab caused a 31% reduction in the risk of death versus placebo after chemoradiation therapy (CRT (HR 0.69, [95% CI, 0.55-0.86]^[411]^[412]^[413]^[414]^[62]^[415]^[332]^[416]^[418].

In the phase III ARCTIC trial, the sub-study B of durvalumab and tremelimumab failed to meet the primary endpoints of a statistically-significant and clinically-meaningful improvement in progression-free survival and overall survival compared to SoC, in patients with non-small cell lung cancer. Updated results showed that median overall survival was 11.5 in the durvalumab + tremelimumab treated patients versus 8.7 months versus standard of care (SoC) treated patients (HR 0.80 [95% CI 0.61, 1.05]; p = 0.109) in the SSB group (sub study B group: 469/600 PD-L1 TC <25% patients were randomized 3:2:2:1 to durvalumab + tremelimumab (durvalumab 20 mg/kg IV + tremelimumab 1 mg/kg IV q4w for up to 12 weekks then D 10 mg/kg IV q2w for 34 weeks). Median progression free survival (PFS) was 3.5 versus 3.5 months 0.77 [0.59, 1.01]; p = 0.056) with 12-month rates of 20.6% and 8.0%. Objective response rate was 14.9 in the durvalumab + tremelimumab treated patients and 6.8% SoC. In SSA group (sub study A group: SoC (as SSA); durvalumab (as SSA); or tremelimumab 10 mg/kg IV q4w for 24 weeks then q12w for 24 weeks), median OS was 11.7 vs 6.8 mo with D vs SoC (HR 0.63 [0.42, 0.93]). 12-mo OS rates were 49.3% and 31.3%. Median PFS was 3.8 versus 2.2 months (HR 0.71 [0.49, 1.04]) with 12-months PFS rates of 19.4% and 9.9%. ORR was 35.5% D and 12.5% SoC^[408]^[409]^[407]^[409].

The phase III MYSTIC trial did not meet its primary endpoint of improving overall survival (OS) compared to standard-of-care (SoC) chemotherapy. Durvalumab monotherapy arm showed a hazard ratio (HR) of 0.76 (97.54%, CI 0.564-1.019; nominal P = 0.036), where as Durvalumab and tremelimumab combination arm (Combination arm) showed HR of 0.85 (98.77%, CI 0.611-1.173; nominal P = 0.202). The overall survival rate after 24 months was 38.3%, 35.4% and 22.7% for durvalumab monotherapy arm, combination arm and standard-of-care (SoC) arm, respectively. Whereas the median overall survival in months was 16.3, 11.9 and 12.9 months, respectively for durvalumab monotherapy arm, combination arm and SoC arm. The median progression free survival in months was 3.9 and 5.4 months for combination arm and SoC arm, respectively. Both combination arm and SoC arm showed progression free survival rate after 12 months as 25.8% and 14.3%, respectively. The trial was conducted in 1 118 patients with stage IV non-small cell lung cancer^[399]^[63]^[398].

Updated results from four years follow-up of the POSEIDON Phase III trial showed that limited course of tremelimumab in combination with durvalumab plus four cycles of chemotherapy, demonstrated a sustained improvement in overall survival (OS) compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). A course of five cycles of tremelimumab added to durvalumab plus platinum-based chemotherapy improved overall survival by 25% compared to chemotherapy alone (hazard ratio [HR] 0.75; 95% CI 0.63-0.88). An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone. A trend for OS improvement continued reported in patients with STK11, KEAP1, and KRAS-mutated mNSCLC when treated with the combination, which reduced the risk of death by 38% (based on a HR of 0.62; 95% CI 0.34-1.12), 57% (based on a HR of 0.43; 95% CI 0.16-1.25), and 45% (based on a HR of 0.55; 95% CI 0.36-0.85), respectively. The combination also extended sustained OS benefit to patients with less than 1% PD-L1 tumor cell expression. Consistent with previous readouts, OS benefit in these updated results appeared more pronounced with tremelimumab plus durvalumab and chemotherapy in patients with non-squamous NSCLC histology. A 32% improvement in OS compared to chemotherapy alone (HR 0.68; 95% CI 0.55–0.85) was reported for patients with non-squamous histology, with an updated median OS of 17.2 months for the combination versus 13.1 months for chemotherapy. An estimated 31.4% of patients with non-squamous NSCLC treated with the combination were alive at three years versus 17.3% for those receiving chemotherapy alone ^[393]. Previous updated results from patients treated with a short course of five cycles of tremelimumab, over 16 weeks in addition to durvalumab and chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options (based on a hazard ratio [HR] of 0.77; 95% CI 0.65-0.92; p = 0.00304). Median OS was 14.0 months versus 11.7 months for chemotherapy. An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI 0.60-0.86; p = 0.00031) with a median PFS of 6.2 months versus 4.8 months, respectively. POSEIDON also tested the combination of durvalumab plus chemotherapy, which demonstrated a statistically significant improvement in PFS (HR=0.74; 95% CI 0.62-0.89; p = 0.00093) versus chemotherapy alone. A positive OS trend observed for durvalumab plus chemotherapy did not achieve statistical significance. Previous results demonstrated statistically significant and clinically meaningful overall survival (OS) benefit versus chemotherapy alone. Though durvalumab plus chemotherapy demonstrated a statistically significant progression-free survival (PFS) benefit versus chemotherapy alone, the overall survival trend was not statistically significant. Earlier results showed that the phase III POSEIDON trial met the primary endpoint in which, durvalumab + tremelimumab combination therapy, added to standard of care (SoC) platinum-based chemotherapy displayed a statistically significant and clinically meaningful improvement in the final progression-free survival (PFS) analysis as first line treatment in patients with metastatic, Stage IV non-small cell lung cancer compared with chemotherapy alone. The PFS was analysed using Blinded Independent Central Review (BICR) assessments according to RECIST 1.1. The trial also achieved secondary endpoint, showing a statistically significant and clinically meaningful PFS improvement vs. chemotherapy alone^[390]^[391]^[392]^[388].

Phase II:

Updated results from a phase II trial showed that the median follow-up of 40 enrolled patients is 24.5 months. Earlier, six of the 30 evaluable patients were progression free at 6 months (Kaplan-Meier, 20.0% [90% CI: 9.7, 33.0]). Partial response was reported in four (13.3%) patients and stable disease, 14 (46.7%) patients. At one year, 4 patients remained progression free (longest PFS ongoing at 80 weeks, n=2). OS-6 and OS-12 was reported to be 59.0 and 44.4%, respectively. The trial is being conducted in 159 patients with glioblastoma^[259]^[260]^[258].

In the phase II trial, treatment with durvalumab and tremelimumab demonstrated improvement in overall survival (OS) and progression free survival (PFS) with a higher disease control rate (DCR) in patients with metastatic colorectal cancer (N = 179). The median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for best supportive care (BSC) (p = 0.07; Hazard ratio (HR): 0.72, 90% CI: 0.54-0.97), with a median follow-up of 15.2 months. Progression free survival (PFS) was 1.8 months and 1.9 months (HR 1.01, 90% CI: 0.76-1.34) for durvalumab and tremelimumab and BSC, respectively. Disease control rate (DCR) was 22.6% for durvalumab and tremelimumab and 6.6% for BSC (p = 0.006). PFS was significantly longer in the patients without liver metastases on durvalumab and tremelimumab (HR: 0.55, 90% CI: 0.31-0.97, p = 0.08, interaction p = 0.02) and DCR was 49% in patients without liver metastases with durvalumab and tremelimumab, compared to 10% in those with liver metastases (odds Ratio: 0.12, 90% CI: 0.05-0.26)^[185]^[184].

Treatment with durvalumab alone, and in combination with tremelimumab, showed efficient anti-tumour activity in patients (n=267) with head and neck cancer, in the phase II CONDOR trial. Out of 267 evaluable patients, 17 of them experienced partial responses to treatment. Overall response rates (ORR) of 9.2% were reported for durvalumab alone, 7.8% for durvalumab + tremelimumab and 1.6% for tremelimumab alone. Out of 17 patients with partial responses, 10 of them were continued with the study as of March 31, 2017. The ORR rate for durvalumab monotherapy was consistent with other single-agent PD-1/PD-L1 inhibitors. Median overall survival was reported 7.6 months for durvalumab + tremelimumab arm, 6 months for durvalumab arm, and 5.5 months for tremelimumab arm. There was no observed difference in clinical activity between durvalumab alone, and in combination with tremelimumab. Responses were measured using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1^[238]^[221].

Updated results from the phase II Apache trial, the combination therapy of durvalumab and tremelimumab, 22 patients had gonadal and seven patients had extragonadal GCT (germ cell tumour). Only one patient showed microsatellite instability in arm A. Two responses (11.1%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) and two stable disease were observed in the expanded arm B. After median follow-up of 16.3 months, 12-month OS in arm A was 30% (95%CI: 7.2-57.7) and in arm B was 29.6% (95%CI: 10.2-52.2). Moreover, chemotherapy post-PD was administered in eight patients (27.6%), but mostly ineffective (7/8 SD/PD). Earlier results from the trial demonstrated signals of activity than durvalumab alone in patients with germ cell cancer. In arm A (n=9), 100% of pts had disease progression (PD), all with features of hyperprogression, 4 had clinical PD and death before restaging. Median increase in sum of tumour diameters (RECIST 1.1) was reported to be 146% with median increase in the elevated serum tumour markers (STM) of 462%. In arm B (n=9), 2 responses (22.2%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) were observed. PD features were similar to arm A. PD occurred in both arms regardless of PD-L1 expression and TMB (PR case: PD-L1 negative and 4 mut/mb)^[642]^[641]^[640].

Preliminary results from the arm A of the phase II BALTIC trial in patients with platinum refractory or resistant extensive-stage small cell lung cancer (SCLC) demonstrated an overall response rate of 9.5% (2 patients; 95% CI 1.17, 30.38). Two patients had partial responses. 5 patients (23.8%) had stable disease and 1 patient (4.8%) had an unconfirmed partial response. The disease control rate (DCR) at 12 weeks was 8/21 (38.1%)^[539]^[538].

Phase I/II

As per the results from the phase I/II study, proteomics-based biomarker evaluable population (BEP) showed shorter median (m) OS compared to intended to treat population. High expression of PD-L1 demonstrated greater OS benefit as expected when treating with durvalumab. 30% of NSCLC patients with high CD 163 protein expression showed poor OS benefit (5 months mOS) following durvalumab treatment. In contrast, patients with PD-L1 TC ≥50% and low CD 163 expression derive greater OS benefit (13.4 months mOS) than those with high CD 163 expression (5 months mOS) or with PD-L1 TC <50% regardless of level of CD 163 expression (4.1-7.4 months mOS). Moreover, patients with poorer outcome have significantly higher baseline CD 163 protein expression as a proportion of total CD 45 protein expression^[592]. Updated results from a phase I/II study, of 103 evaluable patients reported that, complete and partial responders (CR/PRs) showed a significant decrease (Δ = -2.4%, p = 0.02) in cancer panel in plasma (ctDNA) mean variant allele frequencies (VAF) post-treatment with D (i.e. reduction in tumor burden) compared to an increase in mean VAF (i.e. increase in tumor burden) in progressive disease (PD) pts (Δ = +2.7%, p = 0.31). Total mutation count reported was, Δ = -4.6, p = 0.003 in CR/PR compared to Δ = +2.8, p = 0.44 in PD pts. Pts with a decrease in ctDNA VAF at week 6 had longer median progression free survival (PFS) (9.3 mos, 95%CI = [3.0, not reached(NR)] and overall survival (OS) (median NR, 95% CI = [20.3,NR]) compared to those with an increase in VAF (median PFS = 1.4 mos, 95%CI = [1.3,NR];HR = 0.29; p = 0.05 and median OS = 8.2 mos, 95% CI = [2.3,NR]; HR = 0.12; adjusted p = 0.04). DCR was 85%/14% for pts with a decrease/increase in VAF (p =0.002)^[588]. In 21 patients with small cell lung cancer, ORR was 9.5% (2 PR; 95% CI 1.2–30.4) and DCR24 was 14.3% (95% CI 3.0–36.3). Duration of response was 14.6 months for one patient (treatment-naïve), and 29.5+ months for the other patient (platinum refractory with 3 prior lines of therapy), who continued to maintain response 25.5 months after completing protocol-defined initial treatment with durvalumab. Median PFS was 1.5 months (95% CI 0.9–1.8), median OS was 4.8 months (95% CI 1.3–10.4), and 12-month OS rate was 27.6% (95% CI 10.2–48.4)^[587]. Earlier data of 103 evaluable patients showed an ORR of 20.4% (95% confidence interval (CI): 13.1%, 29.5%) and in patients whose tumours expressed PD-L1, the value was 31.1% (95% CI: 19.9%, 44.3%). Median OS was 14.1 months (95% CI: 4.7, not estimable)^[589]. Objective response rate (ORR) of 17.0% (95% CI: 11.9, 23.3) was seen in all evaluable patients with urothelial carcinoma, regardless of PD-L1 status, and 26.3% (95% CI: 17.8, 36.4) in patients with PD-L1 high-expressing tumours when determined by the VENTANA PD-L1 assay. Approximately 14.3% of all evaluable patients achieved partial response and 2.7% achieved complete response. Of patients who had received only neoadjuvant or adjuvant therapy prior to trial entry, 24% (n = 9) responded^[670]. Earlier, additional data from approximately 350 patients enrolled in the expansion phase of the study demonstrated that durvalumab showed signs of clinical activity in a variety of solid tumour types, including NSCLC, squamous cell carcinoma of the head and neck (SCCHN), pancreatic cancer, gastroesophageal cancer, and cutaneous melanoma. Furthermore, data from approximately 150 patients with non-small cell lung cancer treated in the expansion part of the phase I trial showed that durvalumab had clinical activity in this patient population^[591]. Results from the non small cell lung cancer cohort showed that administration of durvalumab as monotherapy demonstrated overall response rate (n = 287) of 25% and 6% in patients with PD-L1- high tumours and in patients with PD-L1-low tumours, respectively. Estimated six-month overall survival (OS) for first-line therapy were 80% and 56% for patients with high PD-L1 expression and low PD-L1 expression, respectively. Furthermore, OS for for second and third-line or greater therapy for patients with high PD-L1 expression was 69%, while for those with low PD-L1 expression was 66% and 53%, respectively. In head and neck cancer cohort (n = 62) overall response rate was 11% (95% CI: 5%, 22% ) and 18% (95% CI: 5%, 40%) in patients with PD-L1-high tumours. OS was 62% (95% CI: 48%-74%) and 42% (95% CI: 27%-55%) in all evaluable patients at six and 12 months, respectively^[248]. Analysis of data from 200 response evaluable patients with NSCLC treated with durvalumab and with 12 weeks or more of follow-up showed an ORR of 16% (27% in PD-L1 positive patients), and DCR (CR, PR or SD for 12 weeks or more) of 42% (48% in PD-L1 positive). ORR was 21% in patients with squamous, and 13% in patients with non-squamous disease. In patients with SCCHN, of 62 response evaluable patients with 24 weeks or more of follow up, ORR was 11% (18% in PD-L1 positive patients), and duration of complete remission for 24 weeks was 15% (18% in PD-L1 positive patients). Six and 12-month OS was 62% (95% CI: 48, 74) and 42% (95% CI: 27, 55), respectively^[590]^[300]. Results from 27 evaluable patients with advanced solid tumours, showed that 19% of patients had a partial response to durvalumab and a further 39% had stable disease, for an overall disease control rate of 58%. Tumour shrinkage was observed across various durvalumab dose levels from as early as 6 weeks. Clinical activity was maintained for at least 1 year. These interim data were from patients enrolled in the dose-escalation part of a phase I trial. Tumour types in patients included in this interim analysis were non-small cell lung cancer (NSCLC), melanoma, colorectal cancer and renal cell carcinoma. In hepatocellular carcinoma patients, ORR was 10.3 months (2.9-24.2), and median overall survival was 13.2 months (6.3-21.1)^[669]^[591]^[220].

Phase I/II

Results of phase I/IIa MEDITREME trial for induction therapy of durvalumab (750 mg/q2W), in combination with tremelimumab (75 mg/q4W) and FOLFOX (6 cycles), in patients with previously untreated RAS-mutated metastatic colorectal cancer (mCRC) demonstrated ORR and DCR of 61% and 89%, respectively. The treatment resulted in 7 complete responses (12%), 29 partial responses (51%), 15 stable diseases (26%). 5 patients (9%) had progression and 1 was not evaluable. Median PFS was 8.4 months [95% CI: 6 months-NR]. 6 months PFS for 6 months was 63.2% [95% CI: 49-74%] and for 12 months was 39% [95% CI: 26-51%]. High baseline levels of Th2 and PDL1+ MDSC were associated with poor PFS^[182]^[181].

Results from phase I/II MOVIE trial met its primary efficacy endpoint. Clinical benefit was observed for 4 patients: 2 PR with durations of 1.6, 3.8 months and 2 SD ≥ 24 weeks. Bayesian estimations of the mean clinical benefit rate (CBR) (95%(CI)) according to the prior distributions defined. PS was 0 (11 pts, 35%) or 1 (20 pts, 65%). 11 pts were still on treatment, 16 stopped for disease progression and 4 for toxicity. With a median follow-up of 12.9 months (1.7–23.4), 16/30 patients showed a CBR; the objective response rate (ORR) was 41.4% (12/29) with 5 CR, 7 PR and 4 SD = 24 weeks^[571]^[570]. In phase I/II MOVIE trial, oral vinorelbine (MOV) combined with tremelimumab (T) and durvalumab (D) demonstrated efficacy in patients (n = 16) with advanced breast cancer. Clinical benefit was observed for four patients, including three partial responses with durations of 15.4, 15.4 and 24.4 weeks and one stable disease (SD) ≥ 24 weeks. In data from 14 patients, one had a complete response^[569]^[568]^[567].

Intermediate results from the phase I/II trial showed that durvalumab had an objective response rate (ORR) of 38.1% in all evaluable patients (95% confidence interval (CI): 18%-47%) and 46% (95% CI: 28%-66%) in patients with PD-L1-high-expressing tumours. In all evaluable patients, disease control rate (DCR) was 48% (95% CI: 32%-64%) and 57% (95% CI: 37%-76%) in patients with PD-L1-high-expressing tumours^[674]^[586]^[220].

Updated data from the phase Ib/II SCORES trial indicated that durvalumab in combination with danvatirsen [see Adis Insight Drug Profile 800021483], exhibited enhanced activity in comparison with durvalumab plus AZD 5069 (CX2i) [see Adis Insight Drug Profile 800030696] or PD-L1 monotherapy in PD-L1 naïve patients with head and neck cancer. Second line therapy with durvalumab plus danvatirsen, demonstrated an objective response rate (ORR) of 26% (95% CI: 13.4% – 43.1%) in PD-L1 naive patients (n = 38), including four complete responses (CRs) and six partial responses (PRs). At the date of cut-off, 7/10 patients in response are still ongoing tretmant and median duration of response (DOR) was not reached (range 5–70+ weeks). Durvalumab and danvatirsen combination therapy produced responses regardless of HPV status or PD-L1 expression. Durvalumab and AZD 5069 (CX2i) combination therapy in PD-L1 naive patients (n = 20), exhibited an ORR of 10% with one CR and one PR. The median DOR was not reached (range 6.7 – 38.4+ weeks)^[249]. Earlier results showed that the combination treatment resulted in 7% of patients achieving a complete tumor response and 23% achieving either a partial or complete tumor response. Durvalumab, in combination with danvatirsen, demonstrated an objective response rate of 29% (8/28 patients), including partial responses in 4 patients and complete responses in 4 patients, in treatment-naive patients (n = 28) with head and neck cancer. An additional eight patients on the treatment combination had stable disease at 12 weeks, which resulted in an overall disease control rate of 57% (16/28). In the combination arm, a complete response was observed in a patient refractory to previous PD-L1 treatment. Previous results from the trial, demonstrated treatment with durvalumab, in combination with AZD 9150, confirmed partial response (PR) per modified iRECIST in two patients with MSH2/6 mutant metastatic castration resistant prostate cancer (mCRPC), and gastro-oesophageal (GE) junction tumour, respectively. In this treatment arm, five patients, including patients with laryngeal cancer, colorectal cancer, and leiomyosarcoma, demonstrated stable disease. The open-label, randomized trial is designed to enrol a total of 465 patients^[250]^[247]^[681]^[248]^[246].

In a phase I/II study, treatment with durvalumab in combination MEDI 0680 in patients with cancer resulted in complete response in 1 patient of bladder cancer cohort. Partial response and stable disease were observed in 3 and 9 patients, respectively. Results were reported from 30 patients enrolled in an open-label study^[617]^[616].

In a phase I/II DREAM trial in patients with malignant pleural mesothelioma, addition of durvalumab to first line treatment with cisplatin and pemetrexed resulted in higher rates of PFS6 and ORR than expected for chemotherapy alone. Interim results from the first 31 evaluable patients (out of 54), PFS6 based on modified RECIST (mRECIST) for MPM was found to be 71%. The objective response rate (ORR) was 61% (using mRECIST) and 53% (using iRECIST)^[312]^[313].

Phase I/II: In a phase I/II study of durvalumab in combination with motolimod in patients with recurrent, platinum-resistant ovarian cancer, 12 patients were progression-free at 6 months. The PFS6 of 30% was indicated (12/40 pts). The data is reported from 40 patients enrolled in a open-label study^[485]^[484]

Updated results from phase Ib/II trial demonstrated in part 2, objective response rate (ORR) was similar across arms with a trend toward longer progression free survival (PFS) and overall survival (OS) in Arm 3 vs Arm 1. There was a trend toward greater clinical benefit in patients with high CD73 expression when comparing Arm A3 vs Arm A1 ^[493] In a phase Ib/II trial conducted in renal cancer, guadecitabine plus durvalumab treatment showed anti-tumour activity. The ORR in six evaluated patients was 33.3% (95% CI, 9.7% - 70%). The median PFS and OS had not reached at the time of data cut off. One year PFS was 83.3% (95% CI: 58.3%)^[517]^[516].

In a phase Ib/II trial, treatment with durvalumab (D), tremelimumab (T), or durvalumab in combination with tremelimumab (D+T) in patients with gastric cancer resulted in consistently reduction in responders but not non-responders after 9 weeks of therapy by circulating tumour DNA (CtDNA) mutation variant allele frequencies (VAFs). A decrease in VAF following 9 weeks of treatment correlated with longer PFS and OS, suggesting utility as an early indicator of clinical benefit. Partial responders (PRs) showed a decrease (Δ = -10.05%, p = 0.26) in VAF post-treatment compared to a significant increase in mean VAF in progressive disease (PD) patients (Δ = +8.14%, p = 0.03). This correlation was also observed in total mutation count in PR (Δ = -6.7, p = 0.17) compared to PD patients (Δ = +2.2, p = 0.06). Patients with a decrease in VAF at week 9 had longer median PFS (5.4 mo [95% CI: 3.7, NR]) and OS (median 13.8 mo [95% CI: 7.0, NR]) compared to those with an increase in VAF (median PFS 1.9 mo [95% CI: 1.8, NR]; HR = 0.33 [95% CI: 0.09, 1.21] and median OS 8.2 months [95% CI: 6.2, NR]; HR = 0.07 [95% CI: 0.01, 0.66]). Updated results showed ORR of 15.8% (95% CI, 3.4%-39.6%) with duration of 13.3 weeks. There was one CR, two partial responses and one stable disease. Duration of median PFS was 1.8 months (95% CI, 1.6-1.9 months), and duration of median overall survival (OS) was 7 months (95% CI, 2.4-7.5 months)^[211]^[209]^[210].

Breast cancer

Phase II:

In the phase II trial, treatment with durvalumab in patients with triple negative breast cancer demonstrated 53.4% pathological complete response (pCR) versus placebo 44.2% (OR 1.45, 95% CI 0.80–2.63, unadjusted Wald p = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR 2.22, 95% CI 1.06–4.64, p = 0.035; interaction p = 0.048). After a median follow-up of 42.2 months, 34 events occurred in 174 patients. 3-year iDFS in pCR vs non pCR was 92.0% versus 71.9% (log-rank p = 0.002). 3-year iDFS was 84.9% with durvalumab versus 76.9% with placebo (HR 0.54, 95%CI 0.27-1.09, stratified log-rank p = 0.0559); 3-year DDFS 91.4% vs 79.5% (HR 0.37, 95%CI 0.15-0.87, p = 0.0148); 3-year OS 95.1% vs 83.1% (HR 0.26, 95%CI 0.09-0.79, p = 0.0076). No difference was seen in iDFS, DDFS and OS between the window and no window cohort^[139]^[140].

Phase I/II:

Treatment with ibrutinib (560mg, daily) + durvalumab, 10 mg/kg every two-week, led to response rates of 3% for breast cancer (1 complete response; duration of response [DOR]: 23 months), 2% for pancreatic cancer (1 partial response; DOR: 10 months), and 0% for NSCLC, in evaluable patients, in a phase Ib/II trial. Median progression-free survival was 2 months in each cohort. Median overall survival was 4, 4, and 8 months in pancreatic cancer, breast cancer, and NSCLC cohorts, respectively. The open–label trial enrolled 124 patients^[579]^[581].

Updated results of the open-label, randomized, phase Ib/II BEGONIA trial to determine the efficacy and safety of durvalumab, in combination with paclitaxel (P), plus capivasertib (C), plus oleclumab (O) observed responses regardless of PD‑L1 expression in patients with untreated, unresectable, locally advanced or metastatic triple negative breast cancer. Confirmed (as of 2 Feb 2023) ORR was 79% (95% CI, 67–88); 6 (10%) patients had complete and 43 (69%) had partial responses. Response to treatment was irrespective of PD-L1 expression level. Median DoR was 15.5 months (95% CI, 9.9–not calculable [NC]). Median PFS was 13.8 months (95% CI, 11–NC)^[150]. At data cutoff of September 2020, in Arm 1 of D+P (N=23), the duration of follow-up was 16.6 months (range 8.5-19.8), confirmed objective response rate (ORR) was 13 (56.5%) [95% CI: 34.5, 76.8, 1 CR, 12 PR, 7 SD and 3 PD], and the percentage with ongoing response at data cutoff was 53.8%. In Arm 2 of D+P+C (N=30), the duration of follow-up was 8.2 months (range 2-21), confirmed ORR was 16 (53.3%) [95% CI: not confirmed; 1 CR, 15 PR, 10 SD and 4 PD], and the percentage with ongoing response at data cutoff was 50.0%. In Arm 5 of D+P+O (N=33), the duration of follow-up was 8.6 months (range 4.1-14.6), confirmed ORR was 16 (53.3%) [95% CI: 28.1, 63.3; 1 CR, 14 PR, 13 SD and 5 PD], and the percentage with ongoing response at data cutoff was 66.7%^[148]. Interim results from the phase I/II BEGONIA trial, treatment with combination therapy durvalumab (D) and paclitaxel (P), demonstrated progression free survival of 7.3 (95% CI: 5.4, 13.8) months, in patients with breast cancer. Confirmed overall response rate (ORR) was reported to be 57% with 54% of those remaining in response at 12 mos (median DoR not reached). Patients receiving D+T-DXd reported confirmed ORR of 100%. Median follow-up time was 2.3 (0–6) months^[147]^[146].

Phase I:

Results from a phase I trial in breast cancer treated with durvalumab and eribulin demonstrated an objective response rate (ORR) of 55% (all partial response) and stable disease in four additional patients, all MBC patients experienced a response to therapy. Median progression free survival (PFS) was 6.2 months. Median overall survival (OS) was not reached^[160]^[161].

In a phase I/II trial, administration of durvalumab in combination with paclitaxel demonstrated an objective response rate in 42% (n=5) patients with median duration of response of 7.1 months. The disease control rate was found to be 67%. Signs of progression was shown by 55% (n=6) patents leaving only one patient each with CR and stable disease. Combination therapy has shown definite increase in survival of triple negative breast cancer patients compared to historical rates of alone^[151]^[152].

Phase I:

Long-term follow-up results of the open-label, phase Ib dose-escalation trial of durvalumab [see AdisInsight drug profile 800020650] in combination with tremelimumab, in patients with non-squamous advanced NSCLC, demonstrated a clinical activity in both PD-L1 ≥25% and <25% groups. The response and survival rates in NSCLC patients (n = 213) with tumour PD-L1 expression, showed a confirmed objective response rate (ORR, CR + PR) in 40 patients (18.8%, 95% CI 13.8–24.7), median duration of response (DOR) of 51.7 weeks (95% CI 40.3–NE), median PFS of 3.5 months (95% CI 1.8–4.0), 12-month overall survival (OS) 53.8% (95% CI 46.4–60.6)^[457]. Interim results demonstrated specific clinical activity was noted in PD-L1 negative patients, who constituted about 70% of NSCLC patients and who were less likely to respond to monotherapy. The confirmed objective response rate (ORR) was obsereved to be 23% (95%; CI 9-44%) in 26 patients of a cohort followed for 24 weeks. Comparable ORRs were seen in patients from this cohort with PD-L1 positive and negative tumours (22% and 29%, respectively)^[458]. Sixty three patients with 16 weeks or more of follow up were evaluable for clinical activity. In the PD-L1 negative patient subset, overall response rate (ORR) was 27% (9/33) and disease control rate (DCR) was 48% (16/33). Overall, almost half of patients in the study achieved a partial response or stable disease, with ORR of 27% (17/63) and DCR of 41% (26/63)^[300]^[456].

Results from the phase II expansion cohort (cohort 3) of the phase I/II trial demonstrated anti-tumour activity of the triplet combination of monalizumab, cetuximab and durvalumab in the first-line treatment of R/M SCCHN. Around 13 out of 40 patients had a confirmed response with a 32.5% overall response rate (95% confidence interval (CI): 20-48), including three complete responses and 7 out of these 13 responders were still on treatment. Median duration of response was not yet reached (95% CI: 7.1-not available). The survival rate at 12 months was 58.6% (95% CI: 45-77) and the median overall survival was 15 months (95% CI: 11.4 - not available). Additionally, in an exploratory subgroup analyses (n=40) according to Combined Positive Score (CPS), which is a PD-L1 scoring method that helps predict response to anti-PD-(L)1 therapy, CPS>1 (n = 25), the subset that had the greatest number of patients, showed a 40% overall response rate (95% CI: 23-59) and median overall survival of 17.3 months (95% CI: 14.7-NA). There were 5 patients with CPS<1, and CPS was unavailable for 10 patients ^[559]. In earlier results, treatment with monalizumab in combination with durvalumab demonstrated anti-tumour activity in patients with recurrent, metastatic colorectal cancer in a phase I trial. Among 39 patients evaluable for efficacy, three (8%) had confirmed partial responses and 11 (28%) had stable disease responses, which included three stable disease patients with tumour reduction, who continued therapy for more than 200 days. The disease control rate was 31% at 16 weeks. Overall response rate (ORR) of 8% was observed and median duration of response was 16.1 weeks at the cut-off date. The open-label, dose-escalation and expansion trial enrolled a total of 55 patients. In the dose-escalation part, 15 patients with selected solid tumours received monalizumab at increasing doses in combination with durvalumab 1500 mg every 4 weeks. In the expansion phase, 40 patients with microsatellite-stable colorectal cancer (MSS-CRC) were enrolled; 58% of patients in expansion had 3+ lines of prior therapy^[553]^[555]^[554]^[677]^[557].

Clinical activity was observed based on interim results from a phase I study of durvalumab plus dabrafenib and/or trametinib in patients with malignant melanoma. Confirmed partial responses in patients with advanced BRAF-mutation positive melanoma were noted in 69% of patients (18/26) receiving the triple combination. The disease control rate (CR, PR or SD) was 100%, and 89% of responders (16/18) had responses after a median follow-up duration of 7.1 months^[300].

In a phase I trial, treatment with the combination therapy of durvalumab and trastuzumab reported no responses by RECIST, with 29% demonstrating stable disease, at week 6 (median duration 2.7 months). All patients had < 1% PD-L1 expression on archival tissue (7/15) or pre-study biopsy (8/15). In the dose expansion cohort, evaluable pre-treatment and on-treatment tumour biopsies (n = 5) showed minimal CD8 cell infiltration^[167]^[166].

Treatment with durvalumab, in combination with tremelimumab, showed overall response rate of 13.3% (2 CR, 2 PR; 95% CI 3.8–30.7), including 3 platinum resistant/refractory patients (1 CR with 2 prior therapies, 2 PR each with 1 prior treatment), tolerated in patients (n=30) with advanced solid tumours, in a phase I trial. Median duration of response was 18.9 months (95% CI 16.3–18.9). At 16 weeks, disease control rate reported was 20% (95% CI 7.7–38.6). Median progression-free survival was 1.8 months (95% CI 1.0–1.9), median overall survival (OS) was 7.9 months (95% CI 3.2–15.8), and 12 month OS rate was reported 41.7% (95% CI 23.3–59.2). Additionally, the company reported that one patient with brain metastasis, was continuing follow-up for more than 2 years after starting treatment^[612]^[611].

In a phase I trial, administration of ramucirumab and durvalumab in patients with solid tumours demonstrated an increased efficacy in patients with high PD-L1 expressing tumors. In patients with non- small cell lung cancer (n=28), objective response rate (ORR) was achieved by 11% (n=3) patients [20 %(1/5) in high PD-L1 expressing tumor patients and 12% (2/17) low PD-L1 expressing tumor patients]. Disease control rate was observed in 57% (n=16) patients [60% (3/5) in high PD-L1 expressing tumor patients and 12% (2/17) in low PD-L1 expressing tumor patients]. Median progression free survival was found to be 2.7 with 4.1 and 2.6 respectively in patients with high and low PD-L1 expressing tumor. The median over survival observed was 11 with 16.4 and 7.5 in patients with high and low PD-L1 expressing tumor respectively. In patients with gastric/gastroesophageal junction cancer (n=29), objective response rate (ORR) was achieved by 21% (n=6) patients with [36 %(5/14) in high PD-L1 expressing tumor patients. Disease control rate was observed in 55% (n=16) patients [71% (10/14) in high PD-L1 expressing tumor patients and 33% (4/12) in low PD-L1 expressing tumor patients]. Median progression free survival was found to be 2.6 with 5.5 and 1.5 respectively in patients with high and low PD-L1 expressing tumor. The median over survival observed was 12.4 with 14.8 and 5.5 in patients with high and low PD-L1 expressing tumor respectively^[604]^[603].

Pooled analysis

The pooled pharmacokinetic exposure-efficacy analysis of the phase I/II 1108 trial and phase II ATLANTIC trial in patients with urothelial carcinoma (UC) and other solid tumours demonstrated that durvalumab 10 mg/kg IV q2w regimen was a recommended dose as single agent in UC patients, and showed no association of pharmacokinetic (PK) exposure with efficacy, overall. The probability of objective response was similar in all quartiles of exposure (p-value ranged from 0.37 to 0.67; n = 96) with no obvious trends between PK exposures and change in tumour size^[439]^[220]^[437].

The pooled analysis of the phase I/II 1108 and phase II ATLANTIC trial in patients with non-small cell lung cancer, showed that absence liver metastases (LM-) was a positive independent predictor of overall survival (OS) and progression free survival (PFS) in both trials. LM− and PDL1 high or low pts had improved OS and PFS vs PDL1 low/LM+; PDL1 high/LM+ pts had improved PFS vs PDL1 low/LM+. LM are associated with shorter survival in D-treated NSCLC pts in 2 trials irrespective of PDL1 status^[438]^[220]^[437].

Results from 332 patients from part two and three from the phase II Study 22 trial, tremelimumab in combination with durvalumab showed that the median OS (95% CI), months in the T300+D was 18.7 (10.8-NR) and 11.3 (8.4-14.6)for the T75+D arm. The ORR (95% CI) in these arms was 22.7 (13.8-33.8) 9.5 (4.2-17.9) respectively^[287]. In updated data from 332 patients from part two and three from the phase II Study 22 trial, tremelimumab in combination with durvalumab resulted in a median overall survival (OS) of 18.7 months. The objective response rate (ORR) was 24% and median duration of response was not reached. Interim data from the study of tremelimumab in combination with durvalumab in hepatocellular carcinoma with or without concomitant HBV or HCV infections demonstrated that confirmed ORR (all partial) were observed in 6 out of 20 uninfected patients while none were observed in the HBV+ and HCV+ populations. One patient out of 11 with HBV+ infection and seven out of 20 uninfected patients displayed complete + partial responses (confirmed + unconfirmed). Number of patients demonstrating CR + PR + stable disease ≥16 wk (DCR16) were 5 (of 11), 4 (of 9) and 14 (of 20) HBV+, HCV+ and uninfected patients respectively. The data was reported from a total of 40 patients^[288]^[667]^[289].

Results from the phase III ARTIC trial showed that median overall survival was 11.5 in the durvalumab + tremelimumab treated patients versus 8.7 months versus standard of care (SoC) treated patients (HR 0.80 [95% CI 0.61, 1.05]; p = 0.109) in the SSB group (sub study B group: 469/600 PD-L1 TC <25% patients were randomized 3:2:2:1 to durvalumab + tremelimumab (durvalumab 20 mg/kg IV + tremelimumab 1 mg/kg IV q4w for up to 12 weekks then D 10 mg/kg IV q2w for 34 weeks). Median progression free survival (PFS) was 3.5 versus 3.5 months 0.77 [0.59, 1.01]; p = 0.056) with 12-month rates of 20.6% and 8.0%. Objective response rate was 14.9 in the durvalumab + tremelimumab treated patients and 6.8% SoC. In SSA group (sub study A group: SoC (as SSA); durvalumab (as SSA); or tremelimumab 10 mg/kg IV q4w for 24 weeks then q12w for 24 weeks), median OS was 11.7 vs 6.8 mo with D vs SoC (HR 0.63 [0.42, 0.93]). 12-mo OS rates were 49.3% and 31.3%. Median PFS was 3.8 versus 2.2 months (HR 0.71 [0.49, 1.04]) with 12-months PFS rates of 19.4% and 9.9%. ORR was 35.5% D and 12.5% SoC^[408]^[409].

Data from a phase I trial conducted in 19 evaluable patients with colorectal cancer and pancreatic cancer showed that the clinical benefit rate at two months of durvalumab and pexidartinib treatment was 21%, two patients with MSI-H CRC had stable disease for more than six months^[620]^[621].

In a phase I trial of adavosertib in combination with durvalumab in patients with advanced solid tumors (n=54) the disease control rate (DCR) for the total cohort was 36%^[606]^[607].

Endometrial cancer

Phase III:

The updated results from the phase III DUO-E trial demonstrated that in the intent-to-treat (ITT) population, carboplatin/paclitaxel (CP) in combination with durvalumab and carboplatin/paclitaxel (CP) in combination with durvalumab and olaparib showed a statistically significant and clinically meaningful progression free survival (PFS) benefit vs CP. Interim OS data were immature (27.7%) yet with a trend towards benefit (CP plus durvalumab vs CP: HR [95% CI] 0.77 [0.56–1.07]; P=0.120; CP plus durvalumab plus olaparib compared to CP: 0.59 [0.42–0.83]; P = 0.003). PFS subgroup analysis showed benefit for both arms vs CP in mismatch repair (MMR) -deficient (dMMR; n = 143) and -proficient (pMMR) pts (n=545). In pMMR pts, maintenance treatment with olaparib further enhanced PFS benefit^[199]. The previous results of phase III DUO-E trial of durvalumab (Imfinzi) demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in the overall trial population of patients with advanced or recurrent endometrial cancer. Results from the analysis of mismatch repair deficient (dMMR) patients showed a similar reduction in the risk of disease progression or death in both Imfinzi plus Lynparza and the Imfinzi Arms, by 59% (HR 0.41; 95% CI 0.21-0.75) and 58% (HR 0.42; 95% CI 0.22-0.80), respectively, versus the Control Arm. Interim overall survival (OS) data showed a favourable trend for both treatment regimens in the overall population. Median PFS was 15.1 months in the imfinzi plus lynparza Arm and 9.6 months in the control arm. In the overall trial population, results showed that treatment with durvalumab plus chemotherapy followed by durvalumab plus olaparib (Imfinzi plus Lynparza Arm) and treatment with durvalumab plus chemotherapy followed by durvalumab monotherapy (Imfinzi Arm) demonstrated a reduction in the risk of disease progression or death, by 45% (hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.43-0.69; p<0.0001) and 29% (HR 0.71; 95% CI 0.57-0.89; p=0.003), respectively, versus chemotherapy alone (Control Arm)^[198]^[197].

Phase

II: Interim analysis from 54 evaluable patients demonstrated complete response in one patient while 3 patients showed partial response with an overall response rate of 14.8% (CI: 6.6-100%) and median duration of response of 16 weeks in the durvalumab arm. The median progression free survival (PFS) was 7.6 weeks while PFS at 24 weeks was 13.3% (CI 6.1-100%). Furthermore, complete response was achieved by 2 patients while one showed partial response in the durvalumab plus tremelimumab arm. The overall response rate for this arm was 11.1% (CI: 4.2-100%) and duration of response was 8 weeks with median PFS of 8.1 weeks and PFS at 24 weeks was 18.5% (CI 10.1-100%)^[648]^[647].

Small cell lung carcinoma:

Phase III

The phase III NEPTUNE trial in patients with non-small cell lung cancer (NSCLC) showed that durvalumab in combination with tremelimumab did not meet the primary endpoint of improving overall survival (OS) as compared with standard of care (SoC) chemotherapy in patients with blood tumour mutational burden (TMB) 20 or more mutations per megabase (mut/Mb)^[402]^[401].

Results showed that the CASPIAN trial met the primary endpoint of reducing the risk of death by 27% (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047). In addition, results for IMFINZI plus chemotherapy showed sustained efficacy after a median follow up of more than three years for censored patients, with a 29% reduction in the risk of death versus chemotherapy alone (based on an HR of 0.71; 95% CI 0.60-0.86; nominal p=0.0003). Updated median OS was reported to be 12.9 months versus 10.5 for chemotherapy. The results showed that 17.6% of patients treated with IMFINZI plus chemotherapy were alive at three years, in comparison to 5.8% of patients treated with chemotherapy alone. Updated analysis of the phase III CASPIAN trial in patients with extensive stage small cell lung cancer, showed sustained efficacy for durvalumab plus chemotherapy after a median follow up of more than two years (OS HR: 0.75; 95% CI 0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone. Across all treatment arms, the subgroup of patients who were progression free at one year had a 75% chance of being alive at two years. In comparison, the subgroup of patients whose disease had progressed within one year (PFS <12 months) had a 10% chance of being alive at two years^[529]^[414]. The trial met the primary endpoint of OS for durvalumab plus chemotherapy by reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI]: 0.59 - 0.91; p = 0.0047), with median OS of 13 months versus 10.3 months for chemotherapy alone. Results also showed an increased confirmed objective response rate for durvalumab plus chemotherapy (68% versus 58% for chemotherapy alone) and that durvalumab added to chemotherapy delayed the time for disease symptoms to worsen^[524]. Interim results showed that treatment with durvalumab plus platinum based chemotherapy improved overall survival, versus platinum based chemotherapy alone [median overall survial 12.9 versus 10.5 months; HR 0.75 (95% CI 0.62 – 0.91; nominal p = 0.0032)]. At two years, 22.2% and 14.4% were alive in the durvalumab plus platinum therapy and platinum therapy alone, respectively. Overall survival improved numerically with durvalumab plus tremelimumab plus platinum therapy (median overall survival 10.4 months with 23.4% patients alive at two years), versus platinum therapy alone, however, statistical significance was not reached [HR 0.82 (95% CI 0.68–1.00; p=0.0451]. Progression free survival and objective response rate improved with durvalumab plus platinum therapy, versus platinum therapy alone. For the durvalumab plus tremelimumab plus platinum therapy, versus platinum therapy alone cohorts, objective reponse rate was 58.5% and 58%, respectively, median progression free survival was 4.9 and 5.4 months, respectively, and 12-month progression free survival rate was 16.9% and 5.3%, respectively. Of 277 with evaluable samples (D + EP, 151; EP, 126), PD-L1 expression was low (5% and 22% of patients with expression ≥1% in tumour cells (TC) and immune cells (IC), respectively). PD-L1 expression as a continuous variable in either TC or IC indicated no significant impact of PD-L1 on Tx effect between arms for OS (P = 0.54 and 0.23, respectively); nor for PFS and ORR. Progression patterns were similar, although fewer patients developed new lesions at first progression with D + EP vs EP (41.4% vs 47.2%), including lung lesions (8.6% vs 15.2%). The incidence of new brain/CNS metastases was similar between arms (11.6% vs 11.5%), despite PCI allowance in the control arm only. Baseline PRO scores were comparable across all symptoms and functional domains. Time to deterioration (TTD) was prolonged across all PROs for D + EP^[665]^[530]^[534]^[531]^[533].

Phase II:

In the phase II trial, treatment with durvalumab in combination with tremelimumab did not show sufficient signal of efficacy for ICI with or without SBRT in relapsed small cell lung carcinoma (SCLC). Best response in 14 overall evaluable patients was progression of disease in nine patients (64.3%), partial response in two (14%) and stable disease in three (21.4%) patients respectively, with a median progression free survival (PFS) of 2.76 months and OS of 4.47 months. There was no significant difference reported in efficacy between Arms A and B but a trend of improved PFS and OS with T/D. Median PFS of 2.1 vs. 3.3 months [HR: 2.44 (0.75-7.93); p = 0.122] and median OS of 2.6 vs. 5.7 months [HR: 1.50 (0.45-4.99); p = 0.5068]^[541]^[542].

In the phase II trial, treatment with tremelimumab in combination with durvalumab (arm A) demonstrated a confirmed objective response rate (ORR) of 7.3% (95% CI 1.54-19.92; 3 partial responses [PR]). The disease control rate (DCR) at 12 weeks was 27%. Out of 12 patients with PD-L1 expression (TC or IC) ≥1%, three patients (25%) had a best response of partial response (PR) or stable disease, compared with 11% (1/9) patients with PD-L1 (TC or IC) <1%. Median progression free survival (PFS) was 1.84 months (95% CI 1.77-1.91) and median overall survival (OS) was 5.36 months (95% CI 2.89-7.23). Patients with baseline MaxVAF in low (n = 9), medium (n = 8) and high (n = 9) tertiles had a median OS of 12.8, 4.5 and 2.3 months, respectively. Patients with a decrease in on-treatment ctDNA level (delta MaxVAF <0) had a longer median OS (12.0 months) vs those with an increase (5.6 months)^[540]^[538].

Treatment with azacitidine in combination with durvalumab for the treatment of acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS) indicated that no statistically significant differences in overall response rate (ORR) between treatment arms were observed in either cohort. In MDS Arm A vs. B, median OS was 11.6 vs. 16.7 months and PFS was 8.7 vs. 8.6 months. In the AML cohort, median OS was 13.0 vs. 14.4 months and PFS was 8.1 vs. 7.2 months. More than 50% of patients were censored. Azacitidine induced similar trends in global hypomethylation, along with focal hypomethylation of PD-L1 and PD-L2 gene loci, at the end of treatment cycle 1 in all treatment groups and cohorts. Mean PD-L1 surface expression in BM immune cells at baseline was highest in monocytes (MDS=1,425; AML=1,536), and then granulocytes (MDS=550; AML=758) and myeloid blasts (MDS=532; AML=735). Increased surface expression of PD-L1 was observed at the end of treatment cycle 3 on BM granulocytes and monocytes from MDS patients and on BM monocytes from AML patients, but no increase was detected on myeloid blasts. The data was released from 213 patients enrolled in a phase II FUSION HR MDS/ELDERLY AML 001 trial^[101]^[102].

Sarcoma

Results from a phase II trial in patients with sarcoma subtypes showed that the median overall survival, 12 month survival and 24 month survival for all patients was 20.8 mo (95% CI: 11.7, NR), 63% (95% CI: 52%, 78%) and 45% (95%CI: 33%, 61%), respectively. For all patients, the mPFS was 4.5 mo (95% CI: 2.8, 6.9). At 12 weeks, 12 months and 24 months the PFS for all pts was 51% (95%CI: 37%, 63%), 28% (95% CI: 18%, 43%), 25% (95% CI: 16%, 41%), respectively. The 12 week PFS was lowest for the LPS cohort (n = 6) at 16% (95% CI: 1%, 52%), and highest for the ASPS cohort (10 pts) at 90% (95% CI: 47%, 99%). Partial responses by irRC were observed in ASPS (5/10), chordoma, (1/5), UPS (1/5), and cutaneous AS (1/1), and 14 patients completed 12 months of therapy. The results were reported from 57 patients^[630]^[629].

Head and neck cancer

Phase II

Results from phase II CheckRad-CD8 trial showed that single cycle induction treatment with cisplatin/ docetaxel plus durvalumab/ tremelimumab significantly reduced stage III-IVB head and neck squamous cell cancer. Eight of 10 patients demonstrated a pathological complete response of their primary tumor defined by complete absence of remaining tumor cells in re-biopsies after induction treatment. The other two patients showed an average intratumoral increase from 227 CD8+ cells/mm² to 1074 CD8+ cells/mm². According to RECIST 1.1 criteria six patients had a partial response (PR), three patients a stable disease (SD), one patient was not evaluable^[226]^[225]. Additional results from the trial demonstrated that induction treatment with cisplatin/ docetaxel plus durvalumab/ tremelimumab achieved a high pathological complete response (pCR) rate. After induction treatment, 27 patients (47%) had a pCR in the re-biopsy and further 25 patients (44%) had a relevant increase of intratumoral CD8+ cells (median increase by factor 3.0). Response according to RECIST criteria was CR in 1 (2%), PR in 19 (33%) and SD in 20 patients (35%) (17 patients not evaluable). In multivariable analysis the intratumoral CD8 density was the only independently significant predictor of pCR (odds ratio 1.0013 per cell/mm², 95%-CI 1.00023-1.0023, p=0.017)In the update results after induction chemo-immunotherapy 41 patients had pCR and 31 an intratumoral CD8+ immune cell increase. Of 60 patients entering RIT (primary endpoint cohort), 10 received DLT and 4 discontinued for other reasons. The feasibility rate of the RIT cohort until cycle 6 was 82%, meeting the primary endpoint of ≥80% (95% confidence interval (CI), one-sided (lower boundary): 72%). The RIT cohort had a PFS rate at 1 year of 79% (CI 69-90%) and at 2 years of 73% (CI 61-87%) and an OS rate at 1 year of 89% (CI 81-98%) and at 2 years of 86% (CI 77-97%). The entire study cohort had a PFS rate at 1 year of 75% (CI 65-85%) and at 2 years of 68% (CI 58-81%) and an OS rate at 1 year of 86% (CI 78-95%) and at 2 years of 80% (CI 70-91%)^[227]^[228].

Updated results from phase I/II trial in patients with head and neck carcinoma demonstrated that the 6moPFS, the main effectiveness objective, was 69.7% (95% CI: 55.6-87.3). PFS was 11.9 months (6.94–14.5) and OS was 25.1 months (17.9–28.4) on average. Eight (24%) patients had no evaluable non-SBRT treated lesion, and the rates of full response, partial response, stable disease, and progressing illness were 9%, 21%, 33%, and 12%, respectively ^[245]. Initial results of the open-label phase I/II trial of durvalumab 1 500 mg plus tremelimumab 75mg plus stereotactic body radiotherapy (SBRT) in 16 evaluable patients with metastatic head and neck carcinoma demonstrated smaller overall tumor burden and bestresponse rates. Global health status scores did not differ statistically between baseline (75) and cycle 3 (73). Of the 14 patients that received SBRT, seven patients had RECIST target lesions untreated by SBRT. The best responses for these seven patients, included one CR, three PR, and three SD. When SBRT treated lesions are included and analysed per RECIST (n = 14), there were nine PR, three SD and two PD. The estimated median progression free survival was 7.2 months^[244]^[243].

In a phase Ib/II trial in patients with HPV-associated recurrent/metastatic head and neck cancer, the overall response rate was 22.2% with three complete responses and three partial responses. Peripheral HPV-specific T cells and tumoural CD8+ T cells were increased^[237]^[236].

Mesothelioma

Results from the phase II trial in patients receiving durvalumab with pemetrexed/cisplatin delivered a promising median overall survival (OS) for previously untreated patients with unresectable mesothelioma. Median overall survival of 21.1 months at the time of report. The 12 month OS rate was 70% with a 2 sided 95% confidence interval (56%, 81%) and two-sided 80% CI (62%, 78%). Initial results from the PD-L1/CD8 staining demonstrated that tumour harbored an average tumor mutation burden of 22 somatic sequence alterations and varying levels of aneuploidy were detected^[316]^[315].

Gastric cancer

Phase III

Positive results from interim analysis of the MATTERHORN phase III trial showed treatment with durvalumab in combination with standard-of-care FLOT neoadjuvant chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel given before surgery) demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of pathologic complete response (pCR) versus neoadjuvant chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. Treatment with durvalumab plus neoadjuvant FLOT chemotherapy resulted in a pCR rate of 19% versus 7% for patients treated with neoadjuvant chemotherapy alone as assessed by blinded independent central review (BICR) (difference in pCR rate 12%; odds ratio [OR] 3.08; p<0.00001). The rate of either complete or near-complete responses was 27% with the durvalumab combination and 14% with neoadjuvant chemotherapy alone. For patients treated with the durvalumab based regimen, 87% completed surgery compared to 84% of patients treated with neoadjuvant chemotherapy alone. In patients who had surgery, including patients with surgery attempted but not completed, the rate of R0 resection (patients having no macroscopic or microscopic residual tumour following surgery) was 86% across both arms. The rate of T0 resection (patients with no evidence of their primary tumour) was 23% for the Imfinzi-based regimen compared to 11% for neoadjuvant chemotherapy alone. The rate of N0 resection (patients with no lymph nodes containing cancer cells) was 52% for the durvalumab based regimen compared to 36%.^[202]^[203].

Ovarian cancer

Updated data from the phase III DUO-O trial showed that paclitaxel/carboplatin (PC) + bevacizumab + durvalumab followed by maintenance (mtx) bevacizumab + durvalumab + olaparib in patients with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm) resulted in a statistically significant and clinically meaningful improvement in PFS vs PC + bevacizumab followed by mtx bevacizumab. At a prespecified interim analysis (DCO Dec 5, 2022), a statistically significant improvement in PFS was observed for Arm 3 vs Arm 1: HR 0.49 (95% CI 0.34–0.69; P < 0.0001) and HR 0.63 (95% CI 0.52–0.76; P < 0.0001) in the HRD+ and ITT populations, respectively; a consistent PFS effect was observed in the HRD- subgroup (HR 0.68, 95% CI 0.54–0.86). A numerical improvement in PFS was shown for Arm 2 vs Arm 1 (ITT population), but statistical significance was not reached^[475]. Interim analysis from the phase III DUO-O trial showed that treatment with a combination of olaparib, durvalumab, chemotherapy and bevacizumab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus chemotherapy plus bevacizumab (control arm) in newly diagnosed patients with advanced high-grade epithelial ovarian cancer without tumour BRCA mutations. Patients were treated with durvalumab in combination with chemotherapy and bevacizumab followed by durvalumab, olaparib and bevacizumab as maintenance therapy. The combination of durvalumab, olaparib chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 37% versus chemotherapy and bevacizumab (hazard ratio (HR) 0.63; 95% CI 0.52-0.76; p<0.0001). Median PFS was 24.2 months versus 19.3, respectively. In the homologous recombination deficiency (HRD)-positive subgroup of patients, durvalumab, olaparib, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 51% versus chemotherapy and bevacizumab alone (HR 0.49; 95% CI 0.34-0.69; p<0.0001). Median PFS was 37.3 months versus 23.0, respectively. At a pre-planned exploratory analysis of the HRD-negative subgroup of patients, durvalumab, olaparib, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 32% versus chemotherapy and bevacizumab (HR 0.68; 95% CI 0.54-0.86). Median PFS was 20.9 months versus 17.4. At the time of this interim analysis, an additional arm evaluating the combination of durvalumab, chemotherapy and bevacizumab demonstrated a numerical improvement in PFS which was not statistically significant (HR 0.87; 95% CI 0.73-1.04; p=0.13). At the time of this planned interim analysis, the overall survival (OS) and other secondary endpoints were immature^[473]^[472].

Results from a phase I/II trial in patients (n=18) with non-mucinous ovarian cancer demonstrated that 9 patients (50%) had disease progression and median progression free survival (PFS) of 14.5 months (95% CI: 9.2 - NA) at 13 months median follow-up. Median overall survival (OS) was not reached. The OS rate at 18 months was 69% (95% CI 0.21 - 0.91). About 83% of the patients had optimal interval tumour reductive surgery (TRS), 70% had a pre-operative response by RECIST (PR=11, CR=1)^[486]^[487].

Updated result from the phase II MEDIOLA trial showed that a prior line of chemotherapy had been administered to 24/32 (75%) olaparib (O)+durvalumab (D) and 20/31 (65%) O+D+bevacizumab (B) patients, respectively. The median follow-up for OS at the data cutoff was 23.2 months for O+D and 31.9 months for O+D+B. For O+D and O+D+B, respectively, the Kaplan-Meier estimates of the median OS (95% CI) were 26.1 (18.7-not calculable [NC]) and 31.9 (22.1-NC) mo. At 12 months and 24 months, the O+D and O+D+B cohorts' respective probabilities of survival (95% confidence intervals) were 77.6 (58.6-88.6) and 96.8 (79.2-99.5), and 50.8 (32.1-66.8) and 64.5 (45.2-78.5), respectively. DCR at 56 weeks (90% confidence interval) was 9.4% for O+D and 38.7% with O+D+B^[550]. In the phase II MEDIOLA study in patients with ovarian cancer, the 24 week disease control rate was 28.1% (90% CI 15.5-43.9) in the olaparib plus durvalumab cohort, and 77.4% (90% CI 61.7-88.9) in the olaparib plus durvalumab plus bevacizumab cohort. The confirmed objective response rate was 31.3% (95% CI 16.1-50.0) and 77.4% (95%CI 58.9-90.4), the median duration of response was 6.9 months (IQR 5.7-11.1) and 11.1 months (IQR 9.0-16.4), and the median progression free survival was 5.5 months (95%CI 3.6-7.5) and 14.7 months (95%CI 10.0-18.1), in the olaparib plus durvalumab, and olaparib plus durvalumab plus bevacizumab cohorts, respectively^[664]^[549].

Results from the phase I/II PINCH trial in patients (n=14) demonstrated high tracer-retention in liver and spleen, most prominent in patients receiving 2 or 10mg durvalumab. ⁸⁹Zr-durvalumab accumulation within tumors and between patients was heterogeneous and not all [¹⁸F]FDG-positive lesions showed ⁸⁹Zr-durvalumab uptake^[240]^[241].

Results from phase II DUTRENEO trial demonstrated that the "cold" arm with 16 patients received CT obtaining a pCR rate of 68.8% (11/16 patients). There were more PDL1 low tumors in the "cold" TIS arm (10/12, 83.3%). pCR rate of 11 (68.8%) in cisplatin-based neoadjuvant chemotherapy (cold) (n = 16), 8 (36.4%) in cisplatin-based neoadjuvant chemotherapy (hot) (n = 22) and 8 (34.8%) in durvalumab (DU) plus tremelimumab (TRE) (hot) (n = 23). One patient in the DU+TRE arm refused radical cystectomy. Full treatment was delivered to 81.3% of CT "cold" vs 59.1% of CT "hot" vs 73.9% in the DU+TRE arm patients^[88]^[89].

Results of the open-label phase II trial in patients (n = 37)with locally advanced oesophageal (LA-EAC) cancer and GEJ adenocarcinoma showed that adjuvant durvalumab following trimodality therapy improved one year RFS to 79.2% compared to historical rate of 50%. Seven patients relapsed, including 11 on treatment, six had late relapses. About 3/5 late relapses were locoregional and were re-treated with chemoradiation. Remaining relapses were systemic with lung and lymph nodes being the most common sites. Two out of three patients who developed grade 3 irAEs are alive and disease free at 17 and 23 months. RFS/OS:1 year- 79.2%/95.5%, 2year-55.5%/67.4%. The HER-2 status in 20/37 patients showed 5/6 HER2 positive patients had disease relapse, one was under treatment^[466]^[465].

In phase II trial, median overall survival was not reached in seven patients with hotspot inactivation mutations in PPP2R1A versus 6.4 months in the 21 patients without such mutations (p = 0.018; HR = 0.13 (95% CI: 0.02-0.95). In several patients, response or prolonged disease stabilisation leading to longer survival occurred after initial progression. The data was released for 28 patients^[480].

In the phase II TRU-D trial, the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer showed that, after neoadjuvant chemotherapy (NAC), the ORR was 86.7% by RECIST v1.1 (95.7% in arm1 and 81.8% in arm2, P = 0.17). At IDS, 30 patients (66.7%) had R0 resection (73.9% in arm1 and 59.1% in arm2, P = 0.353). Fourteen patients (31.1%) had a CRS 3 (39.1% in arm1 and 22.7% in arm2, P=0.337) and 5 (11.1%) had a pathologic remission. Stromal TIL (P = 0.0335), CD8 (P<0.001), CD8/Foxp3 ratio (P<0.001) on immunohistochemistry were significantly increased after NACI. When TILs were analyzed in detail by flow cytometry, suppressive intratumoral regulatory T cells (Treg) were significantly decreased after NACI in both arm (P<0.05). Interestingly, the frequency of intratumoral Treg after neoadjuvant chemo-immunotherapy (NACI) was lower in arm1 than arm2 (P<0.05)^[477]^[476].

Updated results of the randomised, open-label phase Ib/II INEOV trial in patients (n = 64) with unresectable ovarian cancer, including primary peritoneal cancer or fallopian tube adenocarcinoma showed that neoadjuvant carboplatin and paclitaxel (NACP) with durvalumab +/- tremelimumab resulted in encouraging complete resection (CC0) (70%) and pathological response (pCR, 18%) rates, considering whole treatment strategy including delayed interval debulking surgery (IDS) after 6 cycles of neoadjuvant treatment. However, there was no apparent benefit to the addition of tremelimumab to durvalumab. After 3 cycles (C3), 66% (21/32) of patients in NACP + durvalumab 1 125mg alone (NACP + D, arm A) and 59% (19/32) in NACP with tremelimumab 75mg (NACP + T, arm B) had IDS. The 11 patients in arm A not candidate for IDS after C3 crossed over to arm B until 6 cycles (C6) and 5/11 benefited from delayed IDS. The 13 patients in arm B inoperable at C3 went on to receive standard of care (SOC, NACP +/- bevacizumab), and 5/13 became eligible for delayed IDS after C6. Overall, IDS was performed in 50 of 64 evaluable patients, and most (45/50) achieved macroscopically complete resection (CC0), so that the overall CC0 rate was 70% (45/64), with no significant difference between arms (CC0 = 75% vs 65% in arm A vs B). Among the 50 patients who had IDS, complete pathological responses were observed in 18% of patients^[483]. Interim results from the phase Ib/II INEOV neoadjuvant trial showed that the combination of durvalumab (D) +/- tremelimumab (T) with neoadjuvant carboplatin and paclitaxel (NACP) is feasible, and does not compromise chemotherapy delivery and efficacy. Treatment was feasible, 96% (32/36) and 88% (29/33) patients completed C1 to major pathological response rates after 3 cycles (C3) in 9 weeks in arm A and B, respectively. Median interval between C3 and Interval debulking surgery (IDS) was similar in both arms (34 days). IDS was performed in 39/64 evaluable patients and macroscopically complete resection (CCO) achieved in 37 (95%) of them, for an overall CCO rate of 58% (37/64). Chemotherapy response score of 3 (CRS3) including 4 pCR and 2 extra-ovarian pCR was observed in 38% (15/39). There was no significant difference in CCO or major pathological response rates in arm A vs B. The results were obtained from 66 patients with stage IIIC/IV ovarian cancer randomised to C1 of NACP alone (immune microenvironment priming) followed by NACP + D (1125mg) at C2&C3 without (arm A) or with T (75mg) at C2 (arm B) ^[482] ^[481].

Final results of the phase Ib/II CALGB 80803 study showed that addition of adjuvant D to induction FOLFOX and PET-directed CRT prior to surgery was effective with a high rate of pathologic response, and encouraging survival data. Clinical =T3 disease was seen in 32 patients (88.9%, cT4 = 3) and =N1 in 23 (63.9%) patients. PD-L1 CPS was =1 in 25 (71.4%) of 35 tested with 14 (40%) =5. Microsatellite instability (MSI) was identified in 3 (8.3%) patients. 25 (70%) patients were PETr. Three patients had disease progression prior to surgery. pCR was identified in 8 (22.2%) patients and 22 (64.7%) had major pathologic response (MPR; ypTanyN0 + =90% response). Those with MSI tumors had =90% treatment response (1 pCR, 1: ypT1aN0 99% response, 1: ypT2N0, 90% response). 17 (73.9%) of 23 cN+ patients had ypN0 disease. MPR was associated with PD-L1 =1 (p = 0.03) and with a higher tumour mutational burden (TMB; p = 0.016) on MSK-IMPACT testing. Adjuvant D was initiated in 27 patients, with a median number of 6 cycles. Early discontinuation was due to risks of visits due to COVID-2019 (4, 15%), progressive disease (3, 11%), late surgical complications (2, 7%) and immune toxicity (1, 4%). With a median follow-up of 30 months, OS rates were 92% [95%CI: 83%-100%] and 85 % [95%CI: 74%-98%] at 12- and 24-months post induction. 12 and 24-month PFS rates were 81% [95%CI: 69%-95%] and 71% [95%CI: 58%-88%] respectively. In the 33 operated patients, 12 and 24-month disease free survival was 82% [95%CI: 70%-96%] and 78% [95%CI: 65%-94%], respectively. In addition to SUV on PET, total lesion glycolysis (TLG) was correlated with pathologic response. In cases with borderline change in SUV, TLG could predict response to treatment. One PETnr with 30.8% reduction in SUV had 88.1% reduction in TLG and pCR. Conversely, a PETr (-36.3%) who had an increase in TLG (39.3%) had only 40% treatment response on pathology^[207]^[206].

Gastrointestinal cancer

In the phase I CAMILLA trial, preliminary data showed that 19 patients were evaluable for response, 4 partial response (2 advanced GE adenocarcinoma (GEA) and 2 colorectal cancer (CRC)), 12 stable disease, 3 progressive disease; overall response rate (ORR) of 21% and clinical benefit rate of 84% was reported. The median time to PD 16 weeks (range 8-40+). The trial is conduced in 30 patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies^[636]^[635].

Biliary tract cancer (BTC):

Phase III

Updated results from the phase III TOPAZ-1 trial showed that at 3 years, durvalumab combined with chemotherapy reduced the risk of death by 26% versus chemotherapy alone (based on a hazard ratio [HR] of 0.74; 95% confidence interval [CI], 0.63-0.87). The median OS was 12.9 months for IMFINZI plus chemotherapy versus 11.3 months for chemotherapy alone. More than twice as many patients on the IMFINZI-based regimen were alive at three years versus chemotherapy alone (14.6% versus 6.9%)^[121]. Previously, the data demonstrated that the OS and PFS benefit with D + GC v P + GC in the China cohort (hazard ratio [HR], 0.78 and 0.79) were consistent with the global1 and pooled cohorts. OS rates at 12 and 18 months and ORR in the China cohort were numerically higher for D + GC v P + GC. D + GC^[120]. The updated results from the phase III TOPAZ-1 trial demonstrated that the hazard ratio (HR) for durvalumab (D) in combination with gemcitabine and cisplatin (GC) versus placebo in combination with GC, adjusted for disease status, primary tumour location, sex, PD-L1, neutrophil to lymphocyte ratio (NLR), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), liver metastasis, liver involvement (locally advanced or metastatic site in liver/gallbladder), body weight, LDH, albumin and total bilirubin, was 0.70 (95% CI 0.59–0.84). Overall survival (OS) HRs for D in combination with GC versus placebo in combination with GC were <1 across assessed clinical and laboratory factors; no predictive factors for D + GC were found^[119]. Previous updated results from the phase III TOPAZ-1 trial showed that the durvalumab, in combination with standard-of-care chemotherapy demonstrated clinically meaningful benefit. In patients (n=685) median (95% CI) follow-up time was 23.4 (20.6–25.2) months and 22.4 (21.4–23.8) months, respectively. Median (95% CI) overall survival (OS) was 12.9 (11.6–14.1) months with durvalumab plus gemcitabine and cisplatin (D+GC) and 11.3 (10.1–12.5) months. OS HRs (95% CI) favoured D + GC in all prespecified subgroups, including disease status (initially unresectable, 0.79 [0.65–0.95]; recurrent, 0.76 [0.49–1.20]), primary tumour location (intrahepatic cholangiocarcinoma, 0.78 [0.62–0.99]; extrahepatic cholangiocarcinoma, 0.61 [0.41–0.91]; gallbladder cancer, 0.90 [0.64–1.25]) and PD-L1 (tumour area positivity [TAP] ≥1%, 0.75 [0.60–0.93]; TAP <1%, 0.79 [0.58–1.09]). OS rates (D + GC vs PBO + GC) at 12, 18 and 24 months were 54.3% vs 47.1%, 34.8% vs 24.1% and 23.6% vs 11.5%, respectively^[118]. Updated results from the trial showed that the durvalumab, in combination with standard-of-care chemotherapy demonstrated median overall survival (mOS) was numerically greater in patients with an imAE of any grade (17.3 months; 95% CI, 12.4–non-calculable]) vs those without (12.6 months; 95% CI, 10.5–13.6; OS HR 0.62; 95% CI, 0.38–0.97)^[117]. Previously, updated results from the trial showed a clinically meaningful and durable overall survival (OS) benefit. The updated results for durvalumab plus chemotherapy showed enhanced clinical efficacy after an additional 6.5 months of follow-up, demonstrating a 24% reduction in the risk of death versus chemotherapy alone (based on a hazard ratio [HR] of 0.76; 95% confidence interval [CI], 0.64–0.91). Updated median OS was 12.9 months versus 11.3 with chemotherapy. More than two times as many patients were estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%). Results were seen across all prespecified subgroups, regardless of disease status, tumour location or PD-L1 expression. In addition, OS benefit was observed in patients whose tumours stayed the same size (stable disease) as well as in patients whose tumours got smaller or disappeared (responders) ^[116]. Updated results from the trial, demonstrated a consistent overall survival (OS) benefit with an improved OS with durvalumab: intrahepatic cholangiocarcinoma (HR 0.76; 95% CI 0.58-0.98), extrahepatic cholangiocarcinoma (HR 0.76; 95% CI 0.49-1.19) and gallbladder cancer (HR 0.94; 95% CI 0.65-1.37). This consistent OS benefit was observed regardless of geographic location, with patients in North America, Europe and Asia all showing benefit. Durvalumab in combination with standard-of-care chemotherapy demonstrated a statistically significant and clinically meaningful OS benefit versus chemotherapy alone, meeting the primary endpoint^[114]. Addition of durvalumab (D) to gemcitabine and cisplatin (GC) improved OS and there was no difference in Time to deterioration (TTD) of Quality of Life (QoL) for pts, supporting durvalumab (D) + gemcitabine and cisplatin (GC) as a new treatment option for pts with biliary tract cancer (BTC). Compliance rates for PROs were high at baseline (>81%) and remained high (majority >70% over 28 cycles) for both treatment groups. Baseline scores were comparable between treatment groups. Addition of durvalumab (D) was well tolerated, with no significant difference in Time to deterioration (TTD) in durvalumab (D) + GC versus PBO + GC for pt-reported symptoms or functioning using either C30 or BIL21 ,or Global Health Status/Quality of Life (QoL) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.69–1.12; p=0.279)^[115] .The patients experienced a 20% reduction in the risk of death versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI], 0.66-0.97; 2-sided p = 0.021). Investigator-assessed OS rate was 27% (95% CI: 22% - 32%) and 19% (95% CI: 15%-23%) in the durvalumab and placebo arms, respectively. Median overall survival (OS) was 12.8 months versus 11.5 for chemotherapy. An estimated 25% of patients were still alive at two years versus 10% for chemotherapy. Results also showed a 25% reduction in the risk of disease progression or death with durvalumab plus chemotherapy (HR, 0.75; 95% CI, 0.64-0.89; 2-sided p = 0.001). Median progression-free survival (PFS) was 7.2 months for the combination versus 5.7 for chemotherapy. Patients treated with durvalumab plus chemotherapy achieved an objective response rate (ORR) of 26.7% versus an ORR of 18.7% for patients treated with chemotherapy alone^[106]^[113]^[110]^[104].

Phase II

In the phase II trial of tremelimumab and durvalumab, the overall survival (OS) rate at month 6 was reported to be 59.2%. Furthermore, after 12 months, the median OS was 8 months and median PFS was 2.5 months. Complete response (CR) was observed in 1.9% patients, partial response (PR) in 7.8%, and stable disease (SD) in 31.1%, resulting in an objective response rate of 9.7% and a disease control rate of 40.8%^[124]^[123].

Results from phase II trial in patients with biliary tract carcinoma or hepatocellular carcinoma (HCC) indicated that the best clinical response in Arm A were as follows: PR (n=8), SD (n=1), PD (n=1) and in Arm B: SD (n=3), PD (n=5). The median progression free survival (PFS) in the Durva/ Treme Arm A was 3.3 months (95% CI: 1.9-3.9) and Durva/ Treme/ radio frequency ablations (RFA) Arm was 2 months (95% CI: 1.3-2.5)). The median overall survival (OS) in the Durva/ Treme Arm A was 6.1 months (95% CI: 3.5-7.4) and Durva/ Treme/ RFA Arm was 5.7 months (95% CI: 2.9-7.6) ^[295]^[294].

Phase I

Results from a phase I trial in patients with BTC, demonstrated that the C30 global health status (GHS) scores remained stable at all time points and from baseline to post 2 cycles (mean [95% CI] change, 2.66 [-1.10‒6.42]), with greater improvements observed in patients with responder (a best response of complete response (CR) or partial response (PR)) (3.60 [-1.27 to 8.47]) compared to non-responder (stable disease (SD) or progressive disease (PD) (0.66 [-5.19 to 6.51]). For the overall cohort, functioning scales also remained stable from baseline to post 2 cycles. For deterioration of C30 GHS, median deterioration-free survival (months [95% CI]) was 4.14 (2.66-6.47) in all cohorts and there was no difference between responder (3.68 [2.27-7.92]) and non-responder (5.59 [2.73-9.46], Hazard ratio = 1.00 [95% CI, 0.62-1.61], p = 0.997). . In the BMC cohort, frequent mutations were found in DNA damage repair, cell cycle regulation, and genome instability genes (eg, ATM, BRCA2, POLE, MSH2, CDKN2A). Distinct somatic variants were detected in responders versus non-responders. Baseline tissue TMB did not correlate with PFS or OS. Reductions in ctDNA variant allele frequency (VAF) were more prominent among responders during early D+T cycles. ctDNA VAF on C3, D1 was significantly correlated with ORR (P< 0.015). The ORR was ORR (95% CI), % 50.0 in the BMC cohort (n=30) 73.4 (n=45) (60.5-86.3) in the 3C cohort and 73.3 in the 4C cohort (n=46) (60.4-86.2) (32.1-67.9) respectively. The DCR (95% CI), % was 96.7 (90.3-100) 100 (100-100) and 97.8 (93.5-100). The mPFS (95% CI), m13.0 was (10.1-15.9)11.0 (7.0-15.0)11.9 (10.1-13.7)^[127]^[126]^[125]

In a phase II trial, durvalumab and tremelimumab treatment in patients with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origin demonstrated that the median progression free survival-1 (PFS1) at 16.5 months for C1-4 (cohorts) were 5.6 (95%CI: 5-6), 5.8 (95%CI: 3-9), 5.5 (95%CI: 2-9) and 2.4 (95%CI: 2-3) months, respectively. The total number patients evaluated for PFS1 were 123, and 59 (48%) patients were administered with subsequent systemic therapies after progression on durvalumab and tremelimumab treatment. Reported PFS to systemic therapies (PFS2) were 6.5 (95%CI: 6-7), 12.7 (95%CI: 0-26), 7 (95%CI: 6-8) and 8.4 (95%CI: 0.7-16) months for C1-4 respectively. Earlier, the study data demonstrated CBR at 9 months was 7.4%, 32.3%, 25% for C1-3 respectively. OS rate at 9 months for C4 was 36.1% with median follow-up of 10.8 months. The irRECIST overall response rates (irORR) for C1-4 were 7.4%, 0%, 6.3%, 9.1%, respectively. In all groups, except C1 group PD-L1 expression was not enriched for efficacy in either primary or secondary. In C1 group irORR was 16% in patients with PD-L1-positive tumours versus, 0% in patients with PD-L1 negative (p=0.033)^[645]^[644]^[643].

Non-small cell lung cancer

Phase III: Updated positive results from the phase III AEGEAN trial showed that treatment with durvalumab in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) versus neoadjuvant chemotherapy alone followed by surgery for patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC). In the modified intent-to-treat (mITT) population 80.6% durvalumab and 80.7% placebo underwent surgery. Also, 77.6% and 76.7% completed surgery (investigator assessment), with disease progression the most common reason for cancelled (6.8% vs 7.8%) or non-completed surgery (1.4% vs 2.1%). The combination of durvalumab and neoadjuvant chemotherapy also demonstrated a statistically significant and meaningful improvement in pathologic complete response (pCR), a dual primary endpoint, compared to neoadjuvant chemotherapy alone, at a previously reported interim analysis. The final analysis was consistent with these previously announced positive results. In a planned interim analysis of EFS, patients treated with the durvalumab based regimen before and after surgery showed a 32% reduction in the risk of recurrence, progression events or death versus chemotherapy alone (32% data maturity, EFS hazard ratio [HR] of 0.68, 95% confidence interval [CI] 0.53-0.88; p=0.003902). In a final analysis of pCR, treatment with IMFINZI plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6). The trial will continue as planned to assess key secondary endpoints including disease-free survival (DFS) and overall survival (OS)^[379]. Earlier treatment with durvalumab significantly improved event-free survival in AEGEAN phase III trial for patients with resectable non-small cell lung cancer. Results showed that durvalumab-based treatment before and after surgery significantly increased the time patients live without recurrence or progression events. The final pathologic complete response (pCR) and major pathologic response (mPR) analyses were consistent with previously announced positive results^[378]. Earlier results showed a statistically significant and meaningful improvement in pathologic complete response (pCR) as well as in major pathologic response (MPR) compared to neoadjuvant chemotherapy alone ^[380]^[377]^[376]

In a phase II trial, treatment with durvalumab demonstrated radiographic response rate of 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemotherapy (CR: 4.5%, PR: 40.3%, SD: 44.8%) and 58.1% (95%CI: 44.8-70.5) after additional neoadjuvant immunotherapy (CR: 6.5%, PR: 51.6%, SD: 25.8%), in patients with non-small cell lung cancer. Of the 55 resected patients, complete pathological response was reported in 10 patients and a major pathological response defined as =10% viable tumor cells in 33 patients by central pathology review. Postoperative nodal down-staging was reported in 37 patients. One year EFS was reported to be 73.3% (90%CI: 60.1-82.7). Median overall survival was not reached after a median follow up of 28 months^[433]^[432].

Results from a phase II NeoCOAST trial showed that, as previously reported, MPR was numerically higher in all combination arms [durvalumab (D) + oleclumab (O) (n=4/21, 19%), durvalumab (D) + monalizumab (M) (n=6/20, 30%), and durvalumab (D) + danvatirsen (Da) (n=5/16, 31%)], compared with durvalumab (D) monotherapy [n=3/27, 11%]. Among patients with an MPR, 2 had EGFR driver mutations (both D+O arm); KRAS, STK11, RET and ALK alterations were observed in pts without an MPR. Expression of genes associated with NK cells (KLRC1, GNLY) and CD8 T cells (CD8A, GZMK) increased after treatment in all arms; with a greater increase with D+O and D+M (1–5 log2FC, adj p < 0.1) than D alone (0–1 log2FC, n.s.). Tertiary lymphoid structure, interferon, and inflammatory signatures were significantly upregulated after treatment in the D+O and D+M arms. Analysis of ctDNA identified patients who had MR (25–60% per arm after treatment, and 75–100% post-surgery), including patients without an MPR. Association of tumor mutational burden and additional biomarkers with clinical outcomes will be reported. Single cycle of D+O and D+M resulted in greater intra-tumoral immunomodulation than D alone^[426]. In the phase II NeoCOAST trial, treatment with neoadjuvant durvalumab alone or in combination with oleclumab, monalizumab or danvatirsen, for the treatment of patients with non-small cell lung cancer demonstrated that, across all arms, major pathological response (MPR) was more common in patients with baseline tumor PD-L1 expression =1% vs those with <1%. with durvalumab, CD73 expression was correlated with greater residual viable tumor cells at surgery; however, with durvalumab plus oleclumab, high CD73 (=10% tumor cells) was associated with reduced viable tumor cells. Transcriptome analysis of post-treatment and baseline blood samples showed upregulation of genes involved in B cell activation and antigen presentation in pts with MPR in the durvalumab plus oleclumab arm, and upregulation of genes associated with Tregs in patients with MPR in the durvalumab plus monalizumab arm^[425]^[424].

Results from phase II COAST trial demonstrated that oleclumab or monalizumab in combination with durvalumab improved progression-free survival (PFS) and objective response rate (ORR) compared to durvalumab alone in patients with unresectable, stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiation therapy (CRT). After a median follow-up of 11.5 months, the results of an interim analysis showeddurvalumab in combination with oleclumab reduced the risk of disease progression or death by 56% (hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.26-0.75), and in combination with monalizumab by 35% (HR of 0.65; 95% CI 0.49-0.85), when compared to durvalumab alone in stage III NSCLC patients following CRT. The 10-month PFS rate was 64.8% for the durvalumab plus oleclumab combination and 72.7% for durvalumab plus monalizumab, versus 39.2% with durvalumab alone. It also showed an increase in the primary endpoint of confirmed ORR for durvalumabplus oleclumab over durvalumab alone (30% vs. 18%) and for durvalumab plus monalizumab over durvalumab alone (36% vs. 18%). Durvalumab + oleclumab and durvalumab + monalizumab numerically increased ORR (odds ratio [95% CI] 1.83 [0.80, 4.20] and 1.77 [0.77, 4.11] respectively) and significantly improved PFS versus durvalumab alone^[675]^[372]^[373]^[371]

Urothelial bladder cancer:

Updated results from a phase III DANUBE trial in patients with urothelial bladder cancer demonstrated that, all PD-L1 algorithms [with exception of tremelimumab (TC)≥1% for durvalumab] improved the overall survival (OS) HR for durvalumab or durvalumab + tremelimumab vs standard of care (SoC) compared to the all-comers population. Within treatment arms, using the TC/IC25 algorithm, survival was significantly longer in patients with high vs low PD-L1 expression who received either durvalumab + tremelimumab (HR=0.71, p=0.0074) or durvalumab (HR=0.77, p=0.0324) but not standard of care (SoC) (HR=0.98, p=0.895). Both immune cells (IC) and tumour cells (TC) PD-L1 expression contributed to patient selection. Notably, the ability of PD-L1 to predict an OS benefit was impacted by subsequent therapy. In the phase III DANUBE trial, trend toward improvement was observed in median overall survival (OS) between durvalumab and chemotherapy treated patients with high PD-L1 expression as well as between durvalumab plus tremelimumab and chemotherapy arm in the ITT population. However the difference was nor statistically significant between either group. Median OS in PD-L1 high patients treated with durvalumab (n=209) and chemotherapy (n=207) was 14.4 months (95%CI: 10.4–17.3) and 12.1 months (95%CI: 10.4–15.0), respectively [Hazard ratio (95% CI): 0.89 (0.71–1.11); Log-rank P value; 0.3039]. In intent-to-treat (ITT) population; median OS in patients treated with durvalumab plus tremelimumab (n=342) and chemotherapy arm (n=344) was 15.1 months (95%CI: 13.1–18.0) and 12.1 months (95%CI: 10.9-14), respectively [Hazard ratio (95% CI): 0.85 (0.72–1.02); Log-rank P value; 0.0751]80^[85]^[84].

In a phase II trial in patients (n = 17) with urothelial carcinomatrial, durvalumab demonstrated a modest complete response (CR) rate. Among the 13 patients who underwent 6-month mapping biopsy, 3 (18%) patients had a 6-month CR with a median duration of response of 14 months. Progression to muscle invasive or metastatic disease was observed in three patients and nine (53%) underwent radical cystectomy (RC). No correlation was observed between PD-L1 expression and clinical response to durvalumab^[95]^[96].

In the phase Ib portion of the phase Ib/II DEDUCTIVE trial in hepatocellular carcinoma, tivozanib and durvalumab combination demonstrated a 29% partial response (PR) rate and 71% disease control rate (PR + stable disease). The phase Ib portion enrolled seven patients^[279]^[281].

Result from a phase Ib TATTON trial showed that patients (n=180) with non-small cell lung cancer received study treatment, 70 patients provided baseline and progression/discontinuation ctDNA plasma samples. Of these, 45 patients were used for the analysis, 18/70 were not evaluable for ctDNA detection and 7/70 had a PFS of 2 months or shorter. Of the evaluable samples, the following acquired mutations were recorded (exclusivity between genes in most patients); MET D1228X, Y1230X, L1212X (20%, 9/45), EGFR C797X (16%, 7/45), KRAS G12X, G13X (11%, 5/45) and PIK3CA E545K (4%, 2/45). Most patients who developed MET-based resistance (7/9) developed more than one MET mutation, suggestive of polyclonal resistance. Across both Parts B and D, the resistance profiles appeared similar by prior EGFR TKI status and by savolitinib dose^[454]^[453].

Treatment with tremelimumab and durvalumab with stereotactic body radiotherapy (SBRT) showed efficacy, in patients (n=17) with oligometastatic non-small cell lung cancer, in a phase Ib trial. Median PFS and OS are not yet reached^[450]^[451].

Muscle invasive bladder cancer

In phase II IMMUNOPRESERVE study, durvalumab and tremelimumab combination showed high efficacy and bladder preservation in patients with bladder cancer. At post-treatment biopsy, complete response was observed in 26 patients (81%). Two patients had residual muscle invasive bladder cancer and four patients were not evaluated due to rejection, clinical impairment, death from COVID 19 and a suspected treatment-related death from peritonitis. The estimated 6-months rates for disease-free survival (DFS) with bladder intact, DFS and overall survival were 76% (95%CI, 61%-95%), 80% (95%CI, 66%-98%) and 93% (95%CI, 85%-100%), respectively^[92]^[91].

Solid tumour:

Updated results from a phase II trial that evaluated safety and efficacy of olaparib in combination of durvalumab efficacy was not observed. In evaluated 10 patients of the stage I of the trial, partial or complete responses were not observed. DCR was 30% in three patients demonstrating stable disease. There was one patient that continued the treatment for 13.5 months, however the patient was eventually taken off study due to clinical progression. The median PFS was 1.97 months (95% CI 1.73-3.93). Study showed no responses and hence it did not proceed to stage II^[547]. Earlier results in glioma patients (n=9) of combination of olaparib and durvalumab, objective response was seen in one patient with an IDH-mutated glioblastoma who remained on study treatments after 8 cycles. Six patients (67%) had tumour progression after two cycles. Two patients had stable disease as per RECIST but had clinical deterioration and did not continue the combined treatment. Median progression free survival was 2.5 months (range 1.9–8 months)^[545]^[546].

Results from a phase I trial in patients with solid tumours and CNS demonstrated that sPDL1 was completely suppressed in all patients 2 weeks after a single dose of durvalumab. No anti-drug antibody (ADA) were detected in any patients. One objective response was seen in a patient with anaplastic ependymoma by RECIST1.1^[602]^[600] .

Hepatocellular carcinoma

Updated results from the phase III HIMALAYA showed that tremelimumab plus durvalumab demonstrated a sustained, clinically meaningful overall survival (OS) benefit at four years for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were not eligible for localised treatment. At four years of follow-up, a single priming dose of tremelimumab added to durvalumab, called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab), reduced the risk of death by 22% compared to sorafenib (based on a hazard ratio [HR] of 0.78; 95% confidence interval [CI] 0.67-0.92; 78% data maturity). An estimated 25.2% of patients treated with the STRIDE regimen were alive at four years versus 15.1% for those treated with sorafenib. Moreover, treatment effects of the STRIDE regimen versus sorafenib were consistent across all clinically relevant subgroups of patients, as well as those surviving at least three years, regardless of the underlying disease cause (hepatitis B virus [HBV], hepatitis C virus [HCV] or nonviral) or other baseline demographics^[277]. Earlier data from the trial demonstrated that the STRIDE showed a favorable benefit-risk profile compared with S across ALBI subgroups. STRIDE and D monotherapy may represent new uHCC treatment options for patients with less optimal liver function. Patients randomized to STRIDE, D, and S were classified as ALBI grade 1 (n=217, n=198, and n=203, respectively) or ALBI grade 2/3 (n=175, n=191, and n=186, respectively). Baseline demographics and disease characteristics in the sub-groups were similar across treatment arms. In the ALBI grade 1 subgroup, OS HRs (95% CIs) were 0.79 (0.62– 1.01) for STRIDE vs S and 0.91 (0.71– 1.15) for D vs S. Median OS (95% CI) was 23.43 months (19.19– 28.75) for STRIDE, 21.16 months (17.38– 25.86) for D, and 19.02 months (15.67– 23.16) for S; 36-month OS rates were 38.0%, 27.0%, and 27.3%, respectively. In the ALBI grade 2/3 subgroup, OS HRs (95% CIs) were 0.83 (0.65– 1.05) for STRIDE vs S and 0.87 (0.69–1.09) for D vs S. Median OS (95% CI) was 11.30 months (9.33–14.19) with STRIDE, 12.29 months (9.30– 16.03) with D, and 9.72 months (7.23–11.76) with S; 36-month OS rates were 21.8%, 22.5%, and 12.9%, respectively. Objective response rates were numerically higher for STRIDE and D than for S in both ALBI subgroups (Table). Safety in both ALBI subgroups was generally consistent with the full analysis set ^[276]. When subsets were adjusted for prognostic factor imbalances, patients with HBV treated with the STRIDE regimen experienced a 36% reduction in the risk of death versus sorafenib (based on a HR of 0.64, 95% CI 0.47-0.86). Median duration of response was 25.69 months versus 17.00 months for sorafenib. Patients with HCV treated with the STRIDE regimen experienced an 11% reduction in the risk of death versus sorafenib (based on a HR of 0.89; 95% CI 0.63-1.25). Median duration of response was 13.5 months versus 15.7 months for sorafenib. Nonviral patients treated with the STRIDE regimen experienced a 23% reduction in the risk of death versus sorafenib (based on a HR of 0.77; 95% CI 0.59-1.00). Median duration of response was 13.21 months versus 6.01 months for sorafenib. In the past, viral HCC (disease associated with cirrhosis related to chronic hepatitis B or hepatitis C) has been the primary aetiology of the disease. Over the last two decades, the prevalence of non-viral HCC (disease associated with non-viral factors including liver disease, obesity and diabetes) has significantly increased. HIMALAYA was the only phase III trial to demonstrate a survival benefit for immunotherapy in participants with non-viral HCC^[116]. Updated data from phase III HIMALAYA trial in patients treated with the STRIDE (Single Tremelimumab Regular Interval Durvalumab) had better quality of life than those treated with sorafenib, with fewer patients experiencing moderate to severe problems in domains including mobility, self-care, pain/discomfort and anxiety/depression. The trial met its primary endpoint demonstrating a statistically significant improvement of OS with a single priming dose of tremelimumab plus durvalumab every four weeks versus sorafenib. STRIDE regimen improved survival regardless of liver function scores at baseline, with overall survival (OS) hazard ratios (HR) that were generally consistent with the primary analysis in both the ALBI grade 1 subgroup (HR 0.79; 95% confidence interval [CI] 0.62-1.01) and ALBI grade 2/3 subgroup (HR 0.83; 95% CI 0.65-1.05).The overall response rate, duration of response and tolerability profile for STRIDE were consistent regardless of ALBI score. Further, treatment discontinuation was associated with a larger magnitude of worsening health status than disease progression. Following discontinuation, more patients reported experiencing moderate to extreme problems on all domains. These results highlight the impact of treatment discontinuation and the potential quality-of-life benefits for maintaining patients on treatment with the STRIDE regimen^[114]. The positive overall survival (OS) outcomes for STRIDE and durvalumab in pts receiving first-line treatment for uHCC in HIMALAYA were associated with clinically meaningful, pt-centered benefits, demonstrated by delayed worsening of disease-related symptoms, physical functioning (PF), and Global Health Status (GHS)/QoL vs S. Median TTD in months (95% CI) in pt-reported outcomes (PROs)for STRIDE and durvalumab vs sorafenib. Across treatment arms, compliance rates for pt-reported outcomes (PROs) were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. Time to deterioration (TTD) in fatigue, appetite loss, abdominal pain, PF, and GHS/QoL were significantly longer for both STRIDE and durvalumab vs sorafenib. TTD in nausea and abdominal swelling were significantly longer for STRIDE vs sorafenib^[275] . Patients treated with the STRIDE (Single Tremelimumab Regular Interval Durvalumab)regimen experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 96.02% confidence interval [CI] 0.65-0.93; p = 0.0035). Median overall survival (OS) was 16.4 months versus 13.8 for sorafenib. An estimated 31% of patients were still alive at three years versus 20% for sorafenib. An increased in objective response rate (ORR) with the STRIDE regimen versus sorafenib (20.1% vs. 5.1%) were observed. Median duration of response (DoR) was 22.3 months with the STRIDE regimen versus 18.4 with sorafenib. In Imfinzi monotherapy arm, non-inferior OS to sorafenib (HR 0.86; 95.67% CI 0.73-1.03; non-inferiority margin 1.08) with a median OS of 16.6 months versus 13.8 was observed^[273]^[272]

The efficacy data from phase Ib trial of durvalumab in combination with tremelimumab in liver cancer showed potential overall survival. The trial was designed in two cohorts, where cohort A enrolled 3 HCC participants with macrovascular invasion (MVI) and cohort B enrolled 12 participants with Single tremelimumab regular interval durvalumab (STRIDE). The median PFS of cohort B was a significant 2.79 months (95%CI, 1.12–6.64). The 6- and 12-month PFS rates stood at 38.1% and 12.7% respectively. The trial did not determine overall survival, but promisingly, the 6- and 12-month survival rates both reached 87.5%^[296]^[297]

Head and Neck cancer
Phase II
Results from the phase II DuTRe-raD trial, showed that treatment with durvalumab plus tremelimumab in combination with radiotherapy and durvalumab in combination with radiotherapy, was efficacious, in patients with non-resectable locally advanced head and neck cancer. The median PFS was 39 weeks, the 1 year PFS rate was 42%^[231]^[229].

Breast cancer

Phase I/II

Results from the trial (n=54) suggested that olaparib and durvalumab followed by standard neoadjuvant chemotherapy showed very high pathological complete response (pCR) rate in TNBC or low estrogen receptor (ER)+ stage II/III breast cancer. Functional homologous recombination (HR) status as measured by RAD51 foci formation was predictive of early metabolic response to olaparib. gBRCAmt was assessed in 53 patients and 16 (30.1%) harbored pathogenic mutations. Functional HR status as measured by RAD51 foci formation was deficient in 27 (50%) patients and proficient in 27 (50%) patients. Functional HR deficiency was related with early metabolic response by FDG-PET after 2 weeks of olaparib (response in 17/27 HR-deficient tumors [63.0%] vs. 7/27 HR-proficient tumors [25.9%]; p=.006). After 4 weeks of olaparib and durvalumab, HR-deficiency was still related to metabolic response (23/27 vs 17/27, respectively; p=.062) but HR-proficient tumors also showed metabolic decline. Moreover, HR deficiency was also related with RECIST response measured by CT after 4 weeks (17/27 vs. 9/27; p=.029). As of June 2021, 40 patients completed the neoadjuvant treatment and surgery; among those, 30 achieved pCR (pCR rate 75%). Among 13 patients with gBRCAmt who underwent surgery, 11 achieved pCR (84.6%)^[142]^[143].

Combination studies

Results from the phase III MATTERHORN trial showed treatment with durvalumab added to standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) neoadjuvant (before surgery) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of pathologic complete response (pCR) versus neoadjuvant chemotherapy alone for patients with resectable, early-stage and locally advanced (stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers^[663]^[202].

Updated results of the open-label, randomized, phase Ib/II BEGONIA trial of durvalumab for the treatment of breast cancer demonstrated that 56 patients received T-DXd + D (34 ongoing) and 46 were included in the efficacy analysis. Median (range) follow-up was 10.1 (022) months. Median age was 53.5 years, 71% had received prior treatment for early stage BC, and 64% had visceral metastases at baseline. Confirmed ORR was 26/46 (57%; 95% CI, 4171) and unconfirmed ORR was 33/54 (61%; 95% CI, 4774); 1/46 patients (2%) had complete and 25/46 (54%) had partial responses. Confirmed response occurred irrespective of PD-L1 expression (PD-L1 high ORR, 5/7 [71%]; PD-L1 low, 13/21 [62%]; PD-L1 missing, 8/18 [44%]). Median duration of response was not reached; however, 64% of patients remained in response at 12 month follow-up and 73% had an ongoing response at data cutoff. Median PFS was 12.6 months (95% CI, not reached)^[149]. In the phase Ib/II BEGONIA trial, 61 patients showed datopotamab deruxtecan in combination with durvalumab demonstrated an ORR of 73.6% (95% CI, 59.7-84.7) in patients with previously untreated, unresectable, locally advanced or metastatic TNBC (triple-negative breast cancer). Among the 53 evaluable patients, there were four complete response (CRs) and 35 partial responses (PRs). Responses were observed regardless of PD-L1 expression (low and high tumours) with 82% of patients continuing to respond. Twenty-five patients (41.0%) had not received prior treatment for metastatic TNBC. 45 patients remained on study treatment^[129]^[680]. In the phase I/II BEGONIA trial, treatment with combination therapy durvalumab (D) and paclitaxel (P), demonstrated progression free survival of 7.3 (95% CI 5.4–13.8) months, in patients with breast cancer. Confirmed overall response rate (ORR) was reported to be 57% with 54% of those remaining in response at 12 mos (median DoR not reached). Patients receiving D+T-DXd reported confirmed ORR of 100%. Median follow-up time was 2.3 (0–6) months^[147]^[146].

Results from a phase I/II SYNERGY trial showed that the addition of oleclumab to the combination of chemotherapy by carboplatin and paclitaxel with durvalumab as first-line therapy for advanced or metastatic triple-negative breast cancer (mTNBC) did not significantly increase the clinical benefit rate (CBR) at 6 months. Thus, in arm A the CBR was 45% in the overall population with long-lasting responses^[634]^[633].

In the phase I STELLAR-001 trial, in 46 enrolled patients, minimal anti-tumour activity was reported after treatment with combination of avdoralimab and durvalumab. In the hepatocellular carcinoma (HCC) IO naïve cohort, the objective response rate was 4.8% (95% CI: 0.1-23.8) with a median duration of response of 8.3 months (6.5, 10.1). No responses were observed in the other cohorts. Stable disease was observed in 12 (57.1%) HCC IO naïve and 13 (61.9%) NSCLC IO pretreated pts. The median PFS was 3.4 (1.7-5.3) months for the HCC IO naïve cohort and 3.5 (1.9-5.6) months for the NSCLC cohort. Earlier in 12 evaluable patients, one hepatocellular carcinoma (HCC) patient with prior progression after nivolumab, reported a confirmed partial response, while a non-small cell lung cancer (NSCLC) patient who had also progressed after nivolumab, reported prolonged stable disease (40 weeks) ^[575]^[678]^[574].

Small cell lung carcinoma

Phase III:

Results from the study of durvalumab (D) plus platinum-etoposide (EP) in first-line treatment of extensive-stage small cell lung cancer (CANTABRICO) showed that the overall response rate was 51.5% (95%CI 41.8-61.2) (4 complete responses), clinical benefit rate 85.2% (78.3-92.1), median progression free survival (PFS) 6.1 months (m) (5.4-6.8) and 6 m PFS 50.2% (40.4-60.0). Notable differences were found in PFS according number of EP+D cycles received: ≤4 cycles: 5.4m (4.1-6.1), >4 cycles: 6.9m (5.8-10.6), p=0.010)^[324]^[323].

Updated data from the phase I/II neoadjuvant trial of durvalumab for the treatment of breast cancer showed that the pathologic complete response (pCR) rates did not significantly differ between African American (AA) and non-AA patients: 9/21 (43%) AA versus 22/48 (48%) non-AA (p=0.71). 3 year overall survival (OS) was 87% in the non-AA versus 81% in the AA cohort (HR 1.72, 95% CI 0.481-6.136; p=0.405). 3 year event free survival (EFS) were 78.3% and 71.4% in non-AA and AA pts respectively (HR 1.451, 95% CI 0.524-4.017; p=0.474). Patients with pCR were more likely to remain event-free at 3 years, irrespective of race (HR 0.234, 95% CI 0.066-0.829; p=0.024). In multivariate logistic regression analyses, lack of pathologic response (OR for pCR 0.17, 95% CI 0.03-0.7; p=0.02) and node positive status (OR 4.13, 95% CI 1.05-19.88; p=0.05) were associated with recurrence^[156]^[155].

Phase I

Data from the phase I trial suggested that PD-L1 blockade with duvalumab may impact anti-tumor response in patients large B-cell lymphoma undergoing JCAR 014 CAR-T cell therapy. Among the 26 patients evaluated for response the objective response rate (ORR) and the complete response (CR) rate at 3 months were 35% (95% CI, 17-56) and 27% (95% CI, 14-46) respectively. Comparative analysis showed a trend towards lower ORR (P = .08) and CR rate (P = .09) in patients treated with JCAR 014 in combination with durvalumab compared with those treated in the JCAR 014 alone cohort. There were no significant differences in ORR and CR rate between patients in cohort 1 and those who received JCAR014 alone. However, despite a trend towards lower tumor burden, patients treated with durvalumab before JCAR 014 had lower ORR (P = .07) and CR rate (P = .03) compared with those treated in the JCAR 014 alone cohort, and a trend towards lower CR rate compared with those treated with first durvlumab after JCAR 014 (P = .16). Patients treated with JCAR 014 alone had significantly shorter time to CAR-T cell peak counts in blood compared with patients treated with the combination (median of 8 vs. 14 days, P = .01).The open-label, non-randomised trial enrolled 29 patients^[461]^[676]

Pooled analysis

Results from phase I trial in solid tumours showed MEDI 9253 promoted a ≥2-fold increase in tumoral CD8 T cell frequency in 15% patients, and increased PD-L1 expression. Eight out of 10 patients dosed at RP2D in combination with durvalumab were evaluable, including one partial response in a pre-treated melanoma patient, and four prolonged SD^[449]^[447].

Phase I:

Results from a phase I trial in solid tumour patients (n=61) showed that in parts 1A and 1B, 7 patients had partial responses (PRs): 5 confirmed (cPRs) in melanoma (n=2), sarcoma, breast and neuroendocrine cancer (each n=1), and 2 unconfirmed (uPRs) in melanoma and head and neck cancer (each n=1); no patients had PRs in Part 1D. 3/5 patients with cPR had prior anti-PD-(L)1; 2/3 also had prior anti-CTLA-4. For the 5 cPRs, The duration of response (DoR) was 1.9-22.3 months (median not reached); 3 had ongoing PRs and 2 had stable disease (SD) at data cutoff. Non-target injected lesions shrank in 4 patients with cPRs. Overall, 15 patients had SD (including the 2 uPRs)^[60]^[57]

Results from the phase III PACIFIC-2 trial in demonstrated that the trial did not achieve statistical significance for the primary endpoint of progression-free survival (PFS) versus CRT alone for the treatment of patients with unresectable, Stage III non-small cell lung cancer (NSCLC)^[384]^[383].

Non-small cell lung cancer

Phase II

In a phase II trial, durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (nwith unresectable stage III non-small cell lung cancer demonstrated encouraging efficacy in a frailer population. Most had PS 1/2 (59.8%; PS 1, n=67; PS 2, n=3), were aged ≥65 yr (65.8%; age range: 39–85 year), and had stage IIIB/IIIC NSCLC (63.2%). Nearly all had past/present comorbidities (98.3%), mostly vascular (59.0%), respiratory (53.0%) and metabolic (51.3%) disorders. Median treatment duration was 41.0 week (range: 4–108)^[354]^[353].

Data from phase-II DURATION trial showed median overall survival (OS) of 14.3 months for sequential doublet-chemotherapy (dCTX) and 11.1 months for sequential doublet-chemotherapy followed by durvalumab (dCTX-D) (HR 1.2, p=0.46) and 10.2 and 8.3 months for sequential mono-chemotherapy with durvalumab (mCTX-D) and mCTX (HR 0.7, p=0.25) in patients with non-small cell lung cancer (NSCLC). Patients with mCARG =3 had significantly longer OS compared to patients with mCARG >3 in the PP population (11.0 mo vs. 5.3 mo in median, HR 2.10, p<0.001)^[429]^[672]

Cutaneous T-cell lymphoma

Phase I/II

Results from a phase I/II trial demonstrated superior clinical activity of combinatorial durvalumab/lenalidomide as compared with single-agent durvalumab in refractory/advanced cutaneous T-cell lymphoma. The combination therapy achieved a global best ORR of 58%, compared to 36% for the monotherapy. The median follow-up time was 7.9 months (range, 0.9-27.6 months)^[653]^[652].

Indication	Region	Company	Phase	Expected Launch Year	Probability of Success%	Patent Expiry Year	Expected Generic Entry	Last Update
Cancer - 1L bladder (DANUBE)	Wrld (75% US)	-	Development Stopped	-	-	-	-	05 Nov 2023
Cancer - 2L bladder	ex US	Amgen, AstraZeneca	Marketed	2018	100	-	-	05 Nov 2023
Cancer - 2L bladder	US	Amgen, AstraZeneca	Withdrawn	2017	100	-	-	05 Nov 2023
Cancer - Adjuvant NSCLC	Wrld (50% US)	Amgen, AstraZeneca	III	2024	50	-	-	05 Nov 2023
Cancer - HCC (HIMALAYA/EMERALD)	Wrld (50% US)	Amgen, AstraZeneca	Marketed	2022	100	-	-	05 Nov 2023
Cancer - Head & Neck (KESTREL)	Wrld (50% US)	-	Development Stopped	-	-	-	-	05 Nov 2023
Cancer - NSCLC (POSEIDON)	Wrld (50% US)	Amgen, AstraZeneca	Marketed	2022	100	-	-	05 Nov 2023
Cancer - SCLC (CASPIAN)	Wrld (25% US)	Amgen, AstraZeneca	Marketed	2020	100	-	-	05 Nov 2023
Cancer - unresectable lung (PACIFIC)	ex US	Amgen, AstraZeneca	Marketed	2018	100	-	-	05 Nov 2023
Cancer - unresectable lung (PACIFIC)	US	Amgen, AstraZeneca	Marketed	2017	100	-	-	05 Nov 2023
Cancer -last line lung (ARTIC)	Wrld (50% US)	-	Development Stopped	-	-	-	-	05 Nov 2023
Cancer heamatology	Wrld (50% US)	-	Development Stopped	-	-	-	-	05 Nov 2023
Lung Cancer	China	Amgen, AstraZeneca	Marketed	2019	100	-	-	05 Nov 2023

Expected Date	Event Type	Description	Updated
31 Dec 2024	Regulatory Status	AstraZeneca plans to file a regulatory submission for Non-small cell lung cancer (Inoperable/Unresectable, Late stage disease) in 2024 (AstraZeneca pipeline, February 2023)	16 Feb 2023
31 Dec 2024	Regulatory Status	AstraZeneca plans to file a regulatory submission for Liver cancer in 2024 (AstraZeneca pipeline, February 2023)	16 Feb 2023
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Biliary tract cancer (IV), in China in the second half of 2023 ^[111]	23 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for bladder cancer (IV), in the second half of 2023 ^[111]	23 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for bladder cancer (First-line therapy) (IV), in the second half of 2023 ^[111]	23 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Liver cancer (IV), in China in the second half of 2023 ^[111]	23 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Non-small cell lung cancer (Neoadjuvant therapy) (IV), in the second half of 2023 ^[111]	23 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Small cell lung cancer (IV), in the second half of 2023 ^[111]	24 Aug 2022
31 Dec 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Urogenital cancer (First line therapy) in 2H of 2023 (AstraZeneca pipeline, February 2023)	16 Feb 2023
31 Dec 2023	Trial Update	AIM ImmunoTech in collaboration with Erasmus MC and AstraZeneca plans a phase Ib/II DURIPANC trial in Pancreatic cancer (Combination therapy, Metastatic disease) in Netherlands (IV) before the end of 2023 (700360601) ^[662]	12 Jan 2024
16 Oct 2023	Trial Update	AstraZeneca plans a phase II MDT-BRIDGE trial for Non-small cell lung cancer (In adults, In the elderly, Neoadjuvant therapy, First-line therapy) (IV, Infusion) (NCT05925530) (700365306)	13 Mar 2024
11 Aug 2023	Trial Update	AstraZeneca in collaboration with Parexel plans a phase III PATAPSCO trial for non-muscle invasive bladder cancer (First line therapy, Combination therapy, In adults, In elderly) in the US (IV, Infusion) (NCT05943106) (700365721)	21 Jul 2023
31 Jul 2023	Trial Update	AstraZeneca plans a phase III trial for Biliary Tract Cancers (Combination therapy, First-line therapy, Unrespectable, Metastatic disease, Late-stage disease) in July 2023 (NCT05924880) (700365321)	13 Jul 2023
30 Jul 2023	Trial Update	AstraZeneca plans a phase IIIb TOURMALINE trial for Biliary cancer (Combination therapy, First-line therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in USA, France, Germany, Italy, Japan, Singapore, South Korea, Spain, in July 2023 (IV, Infusion) (NCT05771480) (700362606)	28 Sep 2023
14 Jul 2023	Trial Update	AstraZeneca plans a phase III SIERRA trial for Liver cancer (First line therapy, Late stage disease, Combination therapy, In elderly, In adults) in USA, France, Germany, Hong Kong, Italy, Japan, South Korea, Singapore, Spain and Vietnam (IV, Infusion) in July 2023 (NCT05883644) (700364628)	18 Jul 2023
30 Jun 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Non-small cell lung cancer (Inoperable/unresectable, Late-stage disease) (IV), in the first half of 2023 ^[111]	23 Aug 2022
30 Jun 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Liver cancer (Adjuvant therapy) (IV), in the first half of 2023 ^[111]	24 Aug 2022
30 Jun 2023	Regulatory Status	AstraZeneca plans to file a regulatory submission for Non-small cell lung cancer (First-line therapy) (IV), in the first half of 2023 ^[111]	24 Aug 2022
31 Dec 2022	Regulatory Status	AstraZeneca anticipates regulatory decision for Non-small cell lung cancer (First-line therapy, Combination therapy) (IV), in the second half of 2022 ^[111]	23 Aug 2022
31 Dec 2022	Regulatory Status	AstraZeneca anticipates regulatory decision for Liver cancer (First-line therapy, Combination therapy) (IV), in the second half of 2022 ^[111]	23 Aug 2022
31 Dec 2022	Regulatory Status	AstraZeneca anticipates regulatory decision for Biliary tract cancer (IV), in the second half of 2022 ^[111]	06 Sep 2022
31 Dec 2022	Regulatory Status	AstraZeneca plans to file a regulatory submission for Liver cancer (IV), in the first half of 2023	23 Aug 2022
30 Nov 2022	Trial Update	AstraZeneca plans the phase III TREMENDOUS trial for Liver cancer (Combination therapy, First line therapy, Inoperable/Unresectable) (IV) in November 2022 (NCT05557838) (700357351)	24 Mar 2023
30 Sep 2022	Regulatory Status	AstraZeneca anticipates the PDUFA action date for Biliary tract cancer in US in the third quarter of 2022 ^[111]	06 Sep 2022
15 Sep 2022	Trial Update	AstraZeneca plans a phase III LATIFY trial in Non-small cell lung cancer (Combination therapy, Late-stage disease, Second-line therapy or greater, Metastatic disease) (IV, Infusion) in September 2022 (NCT05450692) (700354093)	09 Sep 2022
30 Jun 2022	Trial Update	AstraZeneca plans the phase II SOUND trial for Non-small cell lung cancer (Combination therapy, Late-stage disease, Metastatic disease) (PO), in June 2022 (NCT05374603) (700352142)	25 Jan 2023
01 Mar 2022	Trial Update	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest plans a phase II trial (Combination therapy, Adjuvant therapy) for Biliary tract cancer (NCT05239169) (700348942)	07 Mar 2024
18 Feb 2022	Trial Update	AstraZeneca plans a phase III trial in Non-small cell lung cancer (Combination therapy, Late-stage disease, Inoperable/unresectable) in USA, Australia, Canada, Japan, South Korea, Spain, Taiwan, Thailand, Ukraine, United Kingdom (IV) (NCT05221840)	03 Mar 2022
31 Dec 2021	Regulatory Status	AstraZeneca expects receive regulatory decision for the approval of durvalumab in Small cell lung cancer in China , the Second half of 2021 (3516870)	19 Nov 2020
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Hepatocellular carcinoma (First-line therapy, Combination therapy) in USA, European Union, and Japan in 2021 (AstraZeneca pipeline, February 2018)	06 Jan 2023
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (Adjuvant therapy) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (Neoadjuvant therapy) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (Unresectable/Inoperable, Late stage disease) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (First-line therapy) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Bladder cancer (First-line therapy, Combination therapy) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Liver cancer (First-line therapy, Combination therapy) in 2021 ^[271]	05 Dec 2019
31 Dec 2021	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Liver cancer in 2021 ^[271]	05 Dec 2019
20 Dec 2021	Trial Update	AstraZeneca and Parexel plan the phase II NeoCOAST-2 trial for Non-small cell lung cancer (Neoadjuvant therapy, Adjuvant therapy, Early-stage disease, First-line therapy, Resectable, Combination therapy) (IV), in December 2021 (NCT05061550), (EudraCT2021-003369-37)	15 Apr 2022
31 Oct 2021	Trial Update	M.D. Anderson Cancer Center plans a phase II trial in Pancreatic cancer (Combination therapy, In adults, In the elderly) in the US (IV) in October 2021 (NCT04940286) (700338985)	05 Aug 2023
01 Oct 2021	Trial Update	University of Cincinnati plans a phase II trial for Liver cancer (Combination therapy, First-line therapy) (IV) in October 2021 (NCT05027425)	03 Sep 2021
01 Sep 2021	Trial Update	AstraZeneca plans a phase II CORAL-Lung trial for Non-small cell lung cancer (Combination therapy, Late-stage disease, Metastatic disease, Second-line therapy or greater) in Israel (IV) in September 2021(NCT05000710) (700341299)	19 Jan 2022
31 Aug 2021	Trial Update	AstraZeneca plans a phase III VOLGA trial for Bladder cancer (Combination therapy, In adults, In the elderly, Neoadjuvant therapy) (IV) in August 2021 (NCT04960709) (700339815)	09 Sep 2021
31 Jul 2021	Trial Update	AstraZeneca plans phase II trial for Small-cell lung cancer (First line therapy, Combination therapy, Late-stage disease, Metastatic disease) in Australia (IV, Infusion) in July 2021 (ACTRN12621000586819p) (700337184)	20 May 2021
01 Jun 2021	Trial Update	National Cancer Center (Korea) plans a phase II trial for Gastric cancer (Combination therapy, Metastatic disease, Second-line therapy or greater) (PO, IV) in June 2021 (NCT04893252) (700337277)	25 May 2021
14 May 2021	Trial Update	AstraZeneca plans the phase I/II SCope-D1 trial for Non-small cell lung cancer (Metastatic disease, Second-line therapy or greater) (SC) (NCT04870112) (EudraCT2020-006041-18) (700336598)	30 Jul 2021
14 May 2021	Trial Update	AstraZeneca plans the phase I/II SCope-D1 trial for Small cell lung cancer (Metastatic disease, Combination therapy) in USA, Spain, Taiwan (SC) (NCT04870112) (EudraCT2020-006041-18) (700336598)	30 Jul 2021
01 Apr 2021	Trial Update	AstraZeneca plans a phase 0 trial for Non-small cell lung cancer (Late-stage disease, Metastatic disease) in Australia (ACTRN12621000171819) (700333943)	01 Mar 2021
01 Apr 2021	Trial Update	Gruppo Oncologico del Nord-Ovest plans the phase II INFINITY trial for Gastric cancer (Combination therapy, Neoadjuvant therapy, Second-line therapy or greater, In adults, In the elderly) in Italy in April 2021 (NCT04817826) (700335412)	01 Apr 2021
31 Mar 2021	Trial Update	AstraZeneca plans a phase III trial for Non small cell lung cancer (Late-stage disease, Second-line therapy or greater) in the USA, Australia, Belgium, Czechia, Germany, Greece, Hungary, India, Japan, South Korea, Mexico, Netherlands, Peru, Poland, Spain, Switzerland, Taiwan, Turkey, United Kingdom and Vietnam (NCT04642469)	29 Dec 2020
16 Feb 2021	Trial Update	AstraZeneca plans the phase II TAZMAN trial for Small cell lung cancer (Combination therapy, First line therapy) in Italy, South Korea, Spain (IV) (NCT04745689) (700333510)	24 Mar 2021
31 Dec 2020	Regulatory Status	AstraZeneca expects a decision by the Pharmaceuticals and Medical Devices Agency of Japan on the regulatory submission for durvalumab for Small-cell lung cancer in second half of 2020 ^[382]	25 Aug 2020
31 Dec 2020	Regulatory Status	AstraZeneca expects a decision by the European Union on the regulatory submission for durvalumab for Small-cell lung cancer in second half of 2020 ^[382]	21 Feb 2020
31 Dec 2020	Regulatory Status	FDA assigns PDUFA action date in fourth quarter of 2020 for approved indications of Non-small cell lung cancer and Urogenital cancer ^[41]	03 Sep 2020
31 Dec 2020	Regulatory Status	AstraZeneca announces intention to submit regulatory filings for Non-small cell lung cancer (First-line therapy, Combination therapy with tremelimumab) in China in 2020 (AstraZeneca pipeline, April 2017)	10 Jul 2017
01 Dec 2020	Trial Update	AstraZeneca plans a phase I trial in Solid tumours (In combination, Late stage, Metastatic, In adults, In elderly) in USA (NCT04613492)	19 Jan 2021
30 Nov 2020	Trial Update	AstraZeneca plans the phase III Oriental trial for Small cell lung cancer (Second-line therapy or greater) in China (IV) in November 2020 (NCT04449861) (700324125)	31 Dec 2020
30 Nov 2020	Trial Update	AstraZeneca in collaboration with Daiichi Sankyo Company plans a phase I/II, DESTINY-Breast07 trial for Breast cancer (Combination therapy, First-line therapy, Late-stage disease, Metastatic disease, Second-line or greater) in November 2020 (NCT04538742), (700327385)	19 Jan 2021
27 Nov 2020	Trial Update	AstraZeneca plans a phase III MATTERHORN trial of Durvalumab in Gastric and Gastroesophageal Cancer (Neoadjuvant therapy, Adjuvant therapy, First-line therapy) in Taiwan, in November 2020 (NCT04592913) (700329067)	30 Nov 2020
30 Sep 2020	Trial Update	AstraZeneca plans a phase III DREAM3R trial for Mesothelioma (Combination therapy, First-line therapy, Late-stage disease) in USA and Australia (IV) (NCT04334759) ^[316]	16 Feb 2021
30 Sep 2020	Trial Update	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest and AstraZeneca plans a phase II trial for Liver cancer (Combination therapy, Inoperable/Unresectable, First-line therapy) in Germany in September 2020 (NCT04522544)	25 Aug 2020
30 Sep 2020	Trial Update	AstraZeneca plans a phase III KUNLUN trial for Esophageal cancer (Combination therapy, Inoperable/Unresectable, First-line therapy) in China, Japan, South Korea, Taiwan, Thailand (IV) in September 2020 (NCT04550260) (700327702)	17 Nov 2020
30 Jun 2020	Regulatory Status	FDA assigns PDUFA action date of first quarter of 2020 for durvalumab for Small-cell lung cancer ^[382]	01 Apr 2020
30 Jun 2020	Trial Update	AstraZeneca plans the phase III MERMAID-1 trial for Non-small cell lung cancer in USA, Brazil, Belgium, Bulgaria, Canada, Germany, Israel, Japan, South Korea, Ntherlands, Russia, Spain, Switzerland, Taiwan, Thailand and Turkey (NCT04385368) (700321725)	17 Jul 2020
30 Jun 2020	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Head and Neck cancer (First-line therapy, Combination therapy) in the first half of 2020 ^[271]	05 Dec 2019
30 Jun 2020	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Bladder cancer (First-line therapy, Combination therapy) in the first half of 2020 ^[271]	05 Dec 2019
01 Jun 2020	Trial Update	Jonsson Comprehensive Cancer Center plans a phase II trial for Gynecological Malignancies (Metastatic disease, Second-line therapy or greater, Recurrent, Adjunctive therapy) in US (IV) (NCT04395079) (700322099)	27 Aug 2020
01 Jun 2020	Trial Update	AstraZeneca plans a phase II trial for Non-small cell lung cancer (Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater) (IV, Infusion) (NCT04249362) (700318240)	07 Dec 2023
08 May 2020	Trial Update	Samsung Medical Center plans a phase II trial for small cell lung cancer (Combination therapy, Second-line therapy or greater) in Korea (IV) (NCT04361825) (700321149)	30 Jun 2020
30 Mar 2020	Trial Update	AstraZeneca plans the phase III DUO-E trial for Endometrial cancer (First-line therapy, Monotherapy, Combination therapy, Late-stage disease, Recurrent) (maintenance therapy with or without olaparib after first-line treatment) in March 2020 (NCT04269200) (700318760)	26 Jun 2020
02 Mar 2020	Trial Update	University Health Network in collaboration with AstraZeneca plans to initiate a phase II trial in Non Small Cell Lung Cancer and Renal Cell Carcinoma (Combination therapy, Late-stage disease, Second-line therapy or greater) in Canada (IV) in March 2020 (NCT04262375) (318578)	23 Nov 2020
01 Feb 2020	Trial Update	AstraZeneca plans a phase II trial for Nasopharyngeal cancer (Combination therapy, Inoperable/Unresectable, Recurrent, Late-stage disease, Metastatic disease, Second-line therapy or greater) in February 2020 in the USA (NCT04231864) (700317345) (IV, Infusion)	04 Nov 2020
30 Jan 2020	Trial Update	Medimmune plans a phase II COLUMBIA-2 trial for Microsatellite-stable colorectal Cancer (Combination therapy, adjuvant therapy, First-line therapy) in the US, Canada, France and Spain (IV)(NCT04145193) (700314387)	01 Oct 2020
31 Dec 2019	Regulatory Status	AstraZeneca expects regulatory decision for stage III Non-small cell lung cancer (Inoperable/unresectable) in China in the second half of 2019 ^[331]	17 Dec 2019
31 Dec 2019	Regulatory Status	Astra Zeneca intends to submit regulatory application for Bladder cancer (First-line therapy; Combination therapy) in the second half of 2019 ^[331]	21 Feb 2019
31 Dec 2019	Trial Update	AstraZeneca and MedPacto plans a phase II trial for Urogenital cancer (Combination therapy, Late-stage disease, Second-line therapy or greater) in December 2019 (NCT04064190) (700310598)	23 Aug 2019
31 Dec 2019	Trial Update	AstraZeneca and Shionogi plans the phase Ib/II DURANCE trial for non-muscle invasive Bladder cancer (Combination therapy) (IV) in December 2019 (NCT04106115) (700313267)	28 Apr 2022
31 Dec 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (First line therapy, in combination combination tremelimumab) in USA, European Union, and Japan in 2019 (based on NEPTUNE trial) (AstraZeneca pipeline, February 2018)	21 Feb 2020
31 Dec 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Small cell lung cancer (First-line therapy, Combination therapy) in USA, European Union, and Japan in 2019 (AstraZeneca pipeline, February 2018)	19 Feb 2018
31 Dec 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Urogenital cancer (First-line therapy, Combination therapy) in USA, European Union, and Japan in 2019 (AstraZeneca pipeline, February 2018)	19 Feb 2018
31 Dec 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory filings for Non-small cell lung cancer (First-line therapy, Monotherapy) in China in 2019 (AstraZeneca pipeline, July 2017)	10 Jul 2017
31 Dec 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory filings for Non-small cell lung cancer (First-line therapy, Combination therapy with tremelimumab) in the fourth quarter of 2019 ^[271]	05 Dec 2019
30 Sep 2019	Regulatory Status	FDA intends to assign PDUFA action date for Durvalumab for Non small cell lung cancer (Inoperable/Unresectable) in the third quarter of 2019 ^[331]	21 Feb 2019
30 Sep 2019	Trial Update	AstraZeneca plans the phase II CHIO3 trial for Non-small Cell Lung Cancer (Combination therapy, Neoadjuvant therapy) in the US in September 2019 (IV) (NCT04062708) (700310539)	30 Apr 2021
25 Sep 2019	Trial Update	AstraZeneca plans the phase II SPIRAL-RT trial for Non-small cell lung cancer (First-line therapy, Late-stage disease) in Japan (IV) (JMA-IIA00434) (700310130)	16 Dec 2019
27 Aug 2019	Trial Update	MedImmune plans a phase I trial in Solid tumours (Combination therapy, Late-stage disease, Second-line therapy or greater) in United Kingdom and USA (IV), in August 2019 (NCT03889275) (700305818)	15 Nov 2019
31 Jul 2019	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Head and Neck cancer (First-line therapy, Combination therapy) in USA, European Union, and Japan in the first half of 2019 ^[331]	21 Feb 2019
31 Jul 2019	Trial Update	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and AstraZeneca plan a phase II trial in HPV-16 positive Squamous cell carcinoma (Combination therapy) in USA (IV), in July 2019 (NCT04001413) (700308990)	12 Aug 2019
25 Jul 2019	Trial Update	AstraZeneca plans the phase II WIRE trial for Renal cancer in the United Kingdom (NCT03741426)	20 Nov 2018
01 Jul 2019	Trial Update	AstraZeneca plans a phase I trial for Small cell lung cancer (Combination therapy, First line therapy, Late-stage disease) in the US in July 2019 (NCT03963414) (700307780)	29 May 2019
15 Jun 2019	Trial Update	Jules Bordet Institute and AstraZeneca plans the phase II Neo-CheckRay trial for Breast cancer (Neoadjuvant therapy, Combination therapy) in June 2019 in Belgium (IV) (NCT03875573)	31 Oct 2019
01 May 2019	Trial Update	Yonsei University plans the phase II TRU-D trial for Ovarian cancer (Combination therapy, First-line therapy, Late-stage disease) in South Korea (NCT03899610) (700306107)	04 Jun 2022
29 Apr 2019	Trial Update	AstraZeneca plans a phase III trial for Liver cancer (Combination therapy, Monotherapy, In adults, In the elderly) (IV) in April 2019 (NCT03847428) (EudraCT2018-004105-85)	24 May 2019
26 Apr 2019	Trial Update	AstraZeneca plans the phase III TOPAZ-1 trial for Biliary cancer (Combination therapy, First-line therapy, Late-stage disease, Metastatic disease, Inoperable/unresectable, Recurrent) (IV) in South Korea, Taiwan and Thailand in April 2019 (NCT03875235) (700305504)	13 May 2019
28 Jan 2019	Trial Update	MedImmune plans a phase II trial for Non-small cell lung cancer (Combination therapy) in USA, Canada, France, Italy, Portugal, Spain and Switzerland (NCT03794544)	05 Apr 2019
01 Jan 2019	Trial Update	Samsung Medical Center plans a phase II trial for Solid tumour (Metastatic disease; Combination therapy) in January 2019(700302901), (NCT03780608)	31 Dec 2018
31 Dec 2018	Regulatory Status	Approval for durvalumab for Non-small cell lung cancer(Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater) by the European Commsion is expected in the H2 of 2018 ^[332]	05 Jul 2018
31 Dec 2018	Trial Update	AstraZeneca in collaboration with MedPacto plans a phase Ib/IIa trial for Non-small cell lung cancer (Combination therapy, Metastatic disease) in South Korea in the second half of 2018 ^[11]	27 Jul 2018
31 Dec 2018	Trial Update	AstraZeneca plans the BLASST-2 phase I trial for Bladder Cancer (Neoadjuvant Therapy) in USA (700302681), (NCT03773666)	07 Mar 2019
31 Dec 2018	Trial Update	AstraZeneca plans the PACIFIC 6 phase II trial for Non-small Cell Lung Cancer (Unresectable, Mid-stage disease) in USA, France and United Kingdom (700300310), (NCT03693300)	02 May 2019
31 Dec 2018	Trial Update	AstraZeneca plans the PACIFIC-5 phase III trial for Non small cell lung cancer (Unresectable, Mid-stage disease) in China, South Korea, Taiwan and Turkey (NCT03706690)	21 Feb 2019
31 Dec 2018	Regulatory Status	AstraZeneca announces intention to submit regulatory filings for Head and neck cancer (Second-line therapy or greater, Combination therapy with tremelimumab) in the the US, the EU and Japan in 2018 (AstraZeneca pipeline, July 2017)	10 Jul 2017
20 Dec 2018	Trial Update	AstraZeneca and Myriad Genetic Laboratories plan the phase III DUO-O trial for Ovarian cancer (Late-stage disease, Newly diagnosed, Combination therapy) in USA, Austria, Belgium, Canada, Denmark, Finland, Germany, Hungary, Italy, Japan, South Korea, Spain, and Turkey (IV) (700301623), (NCT03737643)	24 Jan 2019
15 Dec 2018	Trial Update	MedPacto and AstraZeneca plan a phase Ib/IIa trial for PD-L1 positive Non-small cell lung cancer (Metastatic disease, Second-line therapy or greater, Combination therapy) in South Korea (IV) (NCT03732274) (700298211)	15 Nov 2019
01 Dec 2018	Trial Update	AstraZeneca plans the ILLUMINATE phase II trial for Non-small cell lung cancer in Australia (ACTRN12618001742268)	29 Oct 2018
30 Nov 2018	Trial Update	AstraZeneca plans the phase Ib/II BEGONIA trial for Breast cancer (First-line therapy; Metastatic disease, Combination therapy) in USA, South Korea, Taiwan and United Kingdom (IV) (700301772) (NCT03742102)	06 Feb 2019
01 Nov 2018	Trial Update	European Organisation for Research and Treatment of Cancer (EORTC) plans a phase II trial for Non-small cell lung cancer (Late-stage disease, Combination therapy, Second-line therapy or greater) (NCT03319316) (700289727)	10 Sep 2018
05 Oct 2018	Trial Update	AstraZeneca plans a phase III trial for Urothelial cancer (Metastatic disease, Late-stage disease, Combination therapy) in USA, Australia, Brazil, Bulgaria, Canada, Czech Republic, Hungary, Japan, South Korea, Philippines, Poland, Turkey and Vietnam (NCT03682068) (700300041)	29 Oct 2018
01 Sep 2018	Trial Update	Sidney Kimmel Comprehensive Cancer Center plans a phase II trial for Hepatocellular carcinoma (First line therapy) in USA (NCT03638141) (700298984)	10 Apr 2019
31 Jul 2018	Trial Update	Centre hospitalier de l'Université de Montréal and AstraZeneca plan a phase I/II trial for Head and neck squamous cell cancer (Metastatic disease, Combination therapy, Second-line therapy) in Canada (IV) (NCT03283605)	10 Sep 2018
31 Jul 2018	Trial Update	M.D. Anderson Cancer Center and AstraZeneca plans a phase I trial for Cervical cancer and Vulvovaginal cancer (Combination therapy, Recurrent, Metastatic disease) in USA (NCT03452332), in March 2018	13 Aug 2018
31 Jul 2018	Trial Update	AstraZeneca plans the phase II DUTRENEO trial for Bladder cancer (Combination therapy, Late-stage disease, Metastatic disease, Neoadjuvant therapy) in Spain, in July 2018 (NCT03472274)	23 Mar 2020
30 Jun 2018	Regulatory Status	AstraZeneca announces intention to submit regulatory application for Non-small cell lung cancer (Second-line therapy or greater, in combination with tremelimumab) in USA, European Union, and Japan in the first half of 2018 (AstraZeneca pipeline, February 2018)	19 Feb 2018
31 May 2018	Trial Update	AstraZeneca plans the POTOMAC phase III trial for Bladder Cancer (combination therapy) in Australia, Austria, Canada, Germany, Japan, Netherlands, Russia, Spain and United Kingdom (700295970), (NCT03528694)	07 Jun 2018
31 May 2018	Trial Update	AstraZeneca plans a phase I trial for Head and Neck cancer (Adjuvant therapy) in USA (700295976), (NCT03529422)	05 Sep 2018
01 May 2018	Trial Update	Australia New Zealand Gynaecological Oncology Group plans the iPRIME phase II trial for Gynaecological-cancers in Australia (700292516), (ACTRN12618000109202p)	03 Oct 2018
30 Apr 2018	Trial Update	University of Erlangen-Nürnberg Medical School plans the CheckRad-CD8 phase II trial for Head and Neck cancer in Germany (700292943), (NCT03426657)	23 Feb 2020
30 Apr 2018	Trial Update	Washington University School of Medicine and MedImmune plan a phase I trial of durvalumab in combination with a neoantigen DNA vaccine for Breast cancer in USA on 30 September 2017 (700286207)(NCT03199040)	08 May 2018
30 Apr 2018	Trial Update	Massachusetts General Hospital plans a phase II trial for Hepatocellular Carcinoma and Biliary Tract Cancer (Combination therapy, Late-stage disease, Unresectable/Inoperable, Metastatic disease) in USA in April 2018 (NCT03482102) (700294546)	30 May 2018
01 Apr 2018	Trial Update	Columbia University plans a phase I/II trial for T-cell lymphoma (Combination therapy) in USA (NCT03161223)	18 Mar 2019
31 Mar 2018	Trial Update	Samsung Medical Center plans a phase II trial for Head and neck cancer (Combination therapy, Recurrent disease, Metastatic disease, Second-line therapy or greater) in South Korea in March 2018 (NCT03450967) (700293700)	30 Jul 2021
31 Mar 2018	Trial Update	AstraZeneca plans a phase II trial for Bladder cancer (Combination therapy, Late-stage disease, First-line therapy, Inoperable/unresectable, Metastatic disease, In adults, In the elderly) in USA, Canada, South Korea, Russia, Spain and Vietnam in March 2018 (IV) (NCT03459846) (700293941)	06 Apr 2018
05 Mar 2018	Trial Update	AstraZeneca plans a phase Ib/II trial for Solid tumours and Non-small cell lung cancer (Combination therapy, Second-line therapy or greater, First-line therapy, Late-stage disease, Metastatic disease) in United Kingdom in March 2018 (NCT03421353)	23 Mar 2018
31 Jan 2018	Trial Update	AstraZeneca in collaboration with Canadian Cancer Trials Group plans a phase II trial for Oropharyngeal Cancer (Late-stage disease, Combination therapy) in Canada in January 2018 (700292638) (NCT03410615)	10 Sep 2018
01 Jan 2018	Trial Update	Jonsson Comprehensive Cancer Center, AstraZeneca and National Cancer Institute plan a phase I/II trial for Non-small cell lung cancer (Inoperable/Unresectable, Newly diagnosed, Early-stage disease) (NCT03148327)	31 Oct 2017
31 Dec 2017	Trial Update	University Hospital Inselspital and AstraZeneca plans a phase II NITIMIB trial for Bladder cancer (Combination therapy, Neoadjuvant therapy, Second-line therapy) in Switzerland in December 2017 (NCT03234153) (700287437)	25 Jun 2020
25 Dec 2017	Trial Update	AstraZeneca plans a phase II trial for Pancreatic cancer (Adjuvant therapy) (NCT03038477) (700281441)	01 Dec 2017
01 Dec 2017	Trial Update	University College and AstraZeneca plan the RAMPART phase III trial for Renal cell carcinoma (Monotherapy, Combination therapy) (NCT03288532)	05 Jan 2018
30 Nov 2017	Trial Update	AstraZeneca plans a phase II trial for Soft tissue sarcoma (Combination therapy, First-line therapy, Metastatic disease, Recurrent, Late-stage disease) in Germany in November 2017 (NCT03317457) (700289726)	09 Apr 2018
29 Nov 2017	Trial Update	AstraZeneca plans the phase II HUDSON trial for Non-small cell lung cancer (Combination therapy, Second-line therapy or greater, Metastatic disease) in USA, Austria, Canada, Germany and South Korea, in November 2017 (NCT03334617) (700290267)	18 Jan 2018
31 Oct 2017	Trial Update	AstraZeneca and Big Ten Cancer Research Consortium plans a phase Ib/II trial for Renal cancer, Clear cell renal cell carcinoma (Combination therapy, Metastatic disease, Late-stage disease, Second-line therapy or greater) in USA in October 2017 (NCT03308396) (700289460)	20 Feb 2018
30 Oct 2017	Trial Update	AstraZeneca plans the HIMALAYA phase III trial for Hepatocellular carcinoma (First-line treatment, Unresectable/Inoperable) in Brazil, Canada, France, Germany, Hong Kong, India, Italy, Japan, Russia, South Korea, Thailand, Ukraine, USA and Vietnam (NCT03298451)	20 Feb 2018
30 Oct 2017	Trial Update	University of Southern California in collaboration with National Cancer Institute plans a phase Ib trial of guadecitabine and durvalumab for Hepatocellular carcinoma, Pancreatic adenocarcinoma, and Cholangiocarcinoma/Gallbladder cancer (Late-stage disease, Combination therapy) in USA in September 2017 (NCT03257761)	15 May 2018
01 Oct 2017	Trial Update	University Medical Center Groningen and AstraZeneca plan a phase I trial for Non-small cell lung cancer (Combination therapy, Second-line therapy or greater) in Netherlands (NTR6553)	18 Mar 2019
01 Oct 2017	Trial Update	University of California, San Francisco, and MedImmune plan a phase II trial for Bladder cancer (Combination therapy, Monotherapy, Late-stage disease, Metastatic disease) in USA (NCT03150836)	26 Oct 2017
01 Oct 2017	Trial Update	NSABP Foundation plans a phase II trial for Rectal cancer (Late-stage disease, Second-line therapy or greater, Monotherapy) (NCT03102047)	04 Jul 2018
01 Oct 2017	Trial Update	Dana-Farber Cancer Institute and AstraZeneca plan a phase I trial for Gynaecological cancer (Metastatic disease, Second-line therapy or greater, Combination therapy) in USA (IV) (NCT03277482)	16 Feb 2018
30 Sep 2017	Trial Update	Centre Georges Francois Leclerc and AstraZeneca plan a phase I/II trial for Colorectal cancer (Metastatic disease, Combination therapy, First-line therapy, Second-line therapy or greater) in France (NCT03202758)	26 Oct 2017
30 Sep 2017	Trial Update	ARCAGY/GINECO-Group and AstraZeneca plans a phase I/II trial for Ovarian cancer, Fallopian tube cancer, and primary Peritoneal adenocarcinoma(Combination therapy, Monotherapy, First-line therapy, Neoadjuvant therapy) in France in September 2017 (NCT03249142)	26 Oct 2017
30 Sep 2017	Trial Update	University of Wisconsin, AstraZeneca and National Cancer Institute plan a phase I trial for Non-small cell lung cancer (Late-stage disease, Second-line therapy or greater, Combination therapy, Metastatic disease) in USA (IV) (NCT03275597)	17 Mar 2018
31 Aug 2017	Trial Update	M.D. Anderson Cancer Center, AstraZeneca and Stiefel plan a phase I trial for Oropharyngeal cancer (Combination therapy, Monotherapy) in USA (NCT03144778)	31 Aug 2017
31 Jul 2017	Trial Update	M.D. Anderson Cancer Center and AstraZeneca plan a phase I trial for Breast cancer (Combination therapy) in USA (NCT03132467)	13 Sep 2017
31 Jul 2017	Trial Update	Celgene and Singapore General Hospital plan a phase II trial for T-cell lymphoma (Combination therapy, Refractory metastatic disease, Second-line therapy or greater, In adults, In the elderly) in Singapore (NCT03054532)	18 Mar 2019
31 Jul 2017	Trial Update	M.D. Anderson Cancer Center and MedImmune plan a phase II trial for Prostate cancer (Metastatic disease, Combination therapy, First-line therapy, Hormone refractory) in USA (NCT03204812)	27 Jul 2017
30 Jun 2017	Trial Update	AstraZeneca plans the phase III POSEIDON trial in Non-small cell lung cancer (Combination therapy, First-line therapy, Metastatic disease, Late-stage disease) in USA, Hong Kong, South Korea, Peru, Russia, Taiwan, Ukraine and the United Kingdom (NCT03164616) (700284911)	27 Jun 2017
31 May 2017	Trial Update	AstraZeneca plans a phase I/II trial for Sarcoma (Combination therapy, Neoadjuvant therapy, Locally recurrent) in USA (NCT03116529)	07 Jul 2017
15 May 2017	Trial Update	Institut Bergonié, AstraZeneca and PharmaMar plan the TRAMUNE phase I trial for Ovarian cancer and Soft tissue sarcoma (Combination therapy, Metastatic disease, Late-stage disease, Inoperable/unresectable, Second-line therapy or greater) in France (NCT03085225)	13 Jun 2017
30 Apr 2017	Trial Update	Memorial Sloan Kettering Cancer Center, MedImmune and AstraZeneca plan a phase II trial for Colorectal cancer (Metastatic disease, Combination therapy) in USA (NCT03122509)	03 May 2017
30 Apr 2017	Trial Update	Memorial Sloan Kettering Cancer Center and AstraZeneca plan a phase I trial for Thyroid cancer (Metastatic disease, Combination therapy, First-line therapy) (NCT03122496)	03 May 2017
30 Apr 2017	Trial Update	Dana-Farber Cancer Institute and AstraZeneca plan a phase II trial for Mesothelioma (Combination therapy) in USA (NCT03075527)	03 May 2017
21 Apr 2017	Trial Update	AstraZeneca plans a phase III trial for Solid tumours (Monotherapy, Combination therapy, Late-stage disease) in USA and Canada (NCT03084471)	03 May 2017
28 Feb 2017	Trial Update	Canadian Cancer Trials Group plans a phase II trial for Non-small cell lung cancer (Metastatic disease, Late-stage disease, Combination therapy) (NCT03057106)	25 Apr 2017

Organisation	Involvement	Countries
MedImmune	Originator	USA
MedImmune	Owner	USA
Celgene International SARL	Licensee	World
Lung Cancer Research Foundation	Funder	USA
Massachusetts General Hospital	Collaborator	USA
Austin Health	Collaborator	Australia
Kyowa Kirin	Collaborator	Japan
London Health Sciences Centre Research	Collaborator	Canada
AstraZeneca	Collaborator	United-Kingdom
Myriad Genetic Laboratories	Collaborator	USA
University Health Network	Collaborator	Canada
Carisma Therapeutics	Collaborator	USA
Pharmacyclics	Collaborator	USA
Incyte Corporation	Collaborator	USA
Icahn School of Medicine at Mount Sinai	Collaborator	USA
Ontario Institute for Cancer Research	Collaborator	Canada
Grupo Espanol de Tumores Neuroendocrinos	Collaborator	Spain
Northwestern University	Collaborator	USA
National Cancer Institute (USA)	Collaborator	USA
Yale University	Collaborator	USA
Grand Hopital de Charleroi	Collaborator	Belgium
Samsung Medical Center	Collaborator	South-Korea
Cancer Research Institute	Collaborator	USA
University of Colorado at Denver	Collaborator	USA
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori	Collaborator	Italy
Targovax	Collaborator	Norway
Fondazione IRCCS Istituto Nazionale dei Tumori	Collaborator	Italy
Mirati Therapeutics	Collaborator	USA
UNC Lineberger Comprehensive Cancer Center	Collaborator	USA
Washington University School of Medicine	Collaborator	USA
Canadian Cancer Trials Group	Collaborator	Canada
Gilead Sciences	Collaborator	USA
Spanish Lung Cancer Group	Collaborator	Spain
National Health and Medical Research Council	Collaborator	Australia
UNICANCER	Collaborator	France
Cedars-Sinai Medical Center	Collaborator	USA
Celgene Corporation	Collaborator	USA
Rambam Health Care Campus	Collaborator	Israel
Institut Claudius Regaud	Collaborator	France
Syndax Pharmaceuticals	Collaborator	USA
Undisclosed	Collaborator	USA
Charite - Universitatsmedizin Berlin	Collaborator	Germany
Eli Lilly and Company	Collaborator	USA
Jules Bordet Institute	Collaborator	Belgium
Parexel International	Collaborator	USA
MedPacto	Collaborator	South Korea
ARCAGY/GINECO Group	Collaborator	France
NHS Greater Glasgow and Clyde	Collaborator	Scotland
Ottawa Hospital Research Institute	Collaborator	Canada
Daiichi Sankyo Company	Collaborator	Japan
Big Ten Cancer Research Consortium	Collaborator	USA
Childrens Hospital Los Angeles	Collaborator	USA
University of Wisconsin-Madison	Collaborator	USA
Bergonie Institute	Collaborator	France
University of Southern California	Collaborator	USA
Lumos Pharma	Collaborator	USA
Janssen Research & Development	Collaborator	USA
Kyoto Breast Cancer Research Network	Collaborator	Japan
Fundacion CRIS de Investigacion para Vencer el Cancer	Collaborator	Spain
Seoul National University Hospital	Collaborator	South-Korea
Case Comprehensive Cancer Center	Collaborator	USA
Baptist Health South Florida	Collaborator	USA
Centre hospitalier de l'Universite de Montreal	Collaborator	Canada
Xcovery Holdings	Collaborator	USA
Dana-Farber Cancer Institute	Collaborator	USA
M. D. Anderson Cancer Center	Collaborator	Usa
Baylor College of Medicine	Collaborator	USA
Intergroupe Francophone de Cancerologie Thoracique	Collaborator	France
Mary Crowley Cancer Research Center	Collaborator	USA
GSK	Collaborator	United-Kingdom
Avid Bioservices	Collaborator	USA
Novartis	Collaborator	Switzerland
Erasmus MC	Collaborator	Netherlands
New York University School of Medicine	Collaborator	USA
Hamilton Health Sciences	Collaborator	Canada
Immunocore	Collaborator	United-Kingdom
UCLAs Jonsson Comprehensive Cancer Center	Collaborator	USA
Nordic Society of Gynaecological - Clinical Trial Unit	Collaborator	Denmark
University College London	Collaborator	United-Kingdom
Innate Pharma	Collaborator	France
Gustave Roussy	Collaborator	France
European Network of Gynaecological Oncological Trial Groups	Collaborator	Netherlands
University of Glasgow	Collaborator	United-Kingdom
Juno Therapeutics	Collaborator	USA
Radboud University	Collaborator	Netherlands
National Cancer Institute (France)	Collaborator	France
University of Texas M. D. Anderson Cancer Center	Collaborator	USA
Cancer Research UK	Collaborator	United-Kingdom
Sheba Medical Center	Collaborator	Israel
University of Maryland Greenbaum Cancer Center	Collaborator	USA
University of Kansas Medical Center	Collaborator	USA
Biocompatibles International	Collaborator	England
OncoPep	Collaborator	USA
SWOG	Collaborator	USA
AIM ImmunoTech	Collaborator	USA
Institute of Cancer Research	Collaborator	United-Kingdom
Unknown	Collaborator	USA
Spanish Oncology Genito-Urinary Group	Collaborator	Spain
Central European Society for Anticancer Drug Research	Collaborator	Austria
Memorial Sloan-Kettering Cancer Center	Collaborator	USA
Ludwig Institute for Cancer Research	Collaborator	USA
Swiss Group for Clinical Cancer Research	Collaborator	Switzerland
Yonsei University College of Medicine	Collaborator	South-Korea
AVEO Oncology	Collaborator	USA
Centre Leon Berard	Collaborator	France
AIO Studien gGmbH	Collaborator	Germany
Tel-Aviv Ichilov Medical Center	Collaborator	Israel
Gradalis	Collaborator	USA
University of Sydney	Collaborator	Australia
Weill Cornell Medical College	Collaborator	USA

Welcome to AdisInsight

Welcome to AdisInsight