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Apalutamide - Janssen Research and Development

Drug Profile

Apalutamide - Janssen Research and Development

Alternative Names: ARN-509; ERLEADA; Erleada; ERLYAND; JNJ-56021927; JNJ-927

Latest Information Update: 18 Mar 2024

At a glance

  • Originator Aragon Pharmaceuticals; University of California
  • Developer Aragon Pharmaceuticals; Case Comprehensive Cancer Center; Dana-Farber Cancer Institute; Instituto do Cancer do Estado de Sao Paulo; Janssen Research & Development; M. D. Anderson Cancer Center; Singapore General Hospital
  • Class Antiandrogens; Antineoplastics; Aza compounds; Benzamides; Pyridines; Small molecules; Spiro compounds; Sulfhydryl compounds; Thiohydantoins
  • Mechanism of Action Androgen receptor antagonists
  • Orphan Drug Status

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

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Marketed Prostate cancer
  • Phase II Salivary gland cancer

Most Recent Events

  • 25 Jan 2024 Updated efficacy and adverse events data from a phase II trial in prostate cancer presented at the 2024 Genitourinary Cancers Symposium (ASCO-GCS-2024)
  • 25 Jan 2024 Updated efficacy data from the phase III TITAN trial in Prostate cancer presented at the 2024 Genitourinary Cancers Symposium (ASCO-GeCS-2024)
  • 13 Dec 2023 Aragon Pharmaceuticals completes a phase III expanded access protocol trial in Prostate cancer (Adjunctive treatment, Hormone refractory) in Brazil, Mexico and Colombia (PO) (NCT03523338)

Development Overview

Introduction

Apalutamide is an oral small molecule androgen receptor antagonist, being developed by Janssen Research and Development, under a license from University of California System, for the treatment of prostate cancer. Apalutamide being an androgen receptor (AR) inhibitor, prevents the binding of androgen to the androgen receptor and binds itself to the ligand-binding domain of the AR. This binding restrains the nuclear translocation of the AR, DNA binding and also obstructs AR-mediated transcription. It antagonises AR-mediated signalling in AR overexpressing human castration-resistant prostate cancer cell lines. The agent is a second generation anti-androgen, which is designed to treat castration-resistant prostate cancers that have not responded to first generation drugs. The tablet formulation has been launched in the US, and approved in multiple countries. The drug is under regulatory review in Japan for the treatment of hormone-refractory prostate cancer. Clinical development of soft gel capsule and tablet formulations is underway in several countries worldwide.

As at June 2022, no recent reports of development had been identified for phase-I development of apalutamide as a combination therapy for prostate cancer conducted in the US, Belgium, Canada, Italy, Netherlands, Russia and Spain, and as a mono therapy for prostate cancer conducted in China.

The compound was initially being developed by Aragon Pharmaceuticals and emerged from a research programme aimed at developing selective androgen receptor degraders (SARDs) [see AdisInsight drug profile 800038675]. However, the company was acquired by Johnson & Johnson in August 2013 which assigned the development of the drug to its subsidiary, Janssen Research & Development [1] .

Company Agreements

In January 2019, Janssen Pharmaceutical entered into a agreement with Nippon Shinyaku for co-promoting Janssen's apalutamide for patients with castration refractory prostate cancer in Japan. Under the terms of agreement, both companies will be responsible for promotion of apalutamide to the patients and healthcare professionals through appropriate information provision and information gathering. However, marketing authorization rights for apalutamide will be held with Janssen. [2] [3]

In December 2012, the Superior Court of California ruled in favour of Aragon Pharmaceuticals regarding Medivation's breach of contract claim against the University of California. Medivation claimed rights to a series of anti-androgen compounds exclusively licensed to Aragon Pharmaceuticals in 2009, which included JNJ 56021927. The Court ruled that Aragon Pharmaceuticals owned the exclusive rights to these compounds [4] .

Key Development Milestones

In August 2023, Health Canada approved the 240mg once-daily dose tablet for the treatment of non-metastatic castration-resistant prostate cancer(nmCRPC) and metastatic castration-sensitive prostate cancer(mCRPC). In 2021, the 60mg dose tablet was approved by Health Canada for the treatment of Prostate cancer. For patients who have difficulty swallowing whole tablets, the 240mg tablet is approved for additional methods of administration when mixed in non-fizzy beverages or soft foods: orange juice, green tea, applesauce or drinkable yogurt. In addition, ERLEADA® 240 mg tablet can also be administered through a nasogastric tube (NG tube) for patients on enteral tube feeding. In December 2019, Health Canada approved apalutamide, for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). The approval was based on results from the phase III TITAN study [see below]. Earlier, in July 2018, Health Canada approved apalutamide tablets (ERLEADA™), for treatment of patients with non-metastatic castration-resistant prostate cancer(nmCRPC). The approval was based on phase III data from the SPARTAN trial. Earlier, apalutamide was granted priority review status by Health Canada [5] [6] [7] .

In April 2023, Janssen Pharmaceutical announced availability of 240mg tablet an additional tablet strength of ERLEADA® (apalutamide) for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) in the United States [8] .

As of February 2018, apalutamide 240mg (four 60mg tablets; ERLEADA™) od is available in the US for the treatment of non-metastatic, castration-resistant prostate cancer [9] . The FDA approved an NDA for apalutamide in February 2018. In October 2017, Janssen Biotech submitted the NDA to the US FDA [10] . The regulatory submission was based on data from the phase III SPARTAN trial [see below], which evaluated the drug in patients with NM-CRPC, who had rapidly rising prostate-specific antigens (PSA) while receiving continuous androgen deprivation therapy [11] . In December 2017, Janssen announced that the FDA granted Priority Review designation for the NDA [12] . The company was developing both, a tablet and a capsule formulation of apalutamide, however, only tablet formulation was submitted for review (US FDA CDER review document, February 2017).

In September 2019, Janssen Pharmaceutical announced that the US FDA approved apalutamide (ERLEADA®) for the treatment of patients with metastatic castration-sensitive prostate cancer [13] . In April 2019, Janssen Pharmaceuticals had submitted a supplemental New Drug Application (sNDA) to the US FDA seeking approval of apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). The sNDA was based on results from the phase III TITAN study (see below) and will be reviewed by the FDA through the Real-Time Oncology Review (RTOR) programme [14] .

Apalutamide (Erlyand®) was approved in Australia, in July 2018, for the treatment of non-metastatic, castration-resistant prostate cancer. The product has also been approved for the same indication in Brazil (ERLEADA®) and Argentina [15] [15] [16] .

In March 2018, Janssen Pharmaceutical submitted a New Drug Application (NDA) seeking marketing and manufacturing approval of apalutamide to the Ministry of Health, Labor and Welfare (MHLW), Japan, for the treatment of castration resistant prostate cancer [17] .

In January 2020, Janssen Pharmaceuticals announced that the European Commission has approved the expanded approval of apalutamide for the treatment of patients with metastatic hormone-sensitive prostate cancer. The approval was based on the phase III TITAN study [see below]. Earlier, in June 2019, Janssen Pharmaceuticals announced the submission of a Type II variation to the European Medicines Agency (EMA) seeking approval of apalutamide for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of extent of disease or prior docetaxel treatment history. The submission was based on the results from phase III TITAN study [see below] [18] [19] .

In January 2018, Janssen Pharmaceuticals announced that the European Commission (EC) has granted marketing authorisation apalutamide for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease [20] . Previously, in November 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the approval [21] . Marketing Authorisation Application for the same was submitted to the European Medicines Agency (EMA) in February 2018. The submission was based on data from the phase III SPARTAN trial [see below] [22] .

In May 2020, the Japanese Ministry of Health, Labour and Welfare (MHLW) granted an expanded approval for the usage of apalutamide tablet (60mg), for the treatment of male patients with prostate cancer, bearing a distant metastases. Earlier, in May 2019, Janssen Pharmaceuticals submitted supplemental registration dossiers to the MHLW seeking this approval [23] [19] .

In August 2023, Janssen Research & Development initiated a phase III LIBERTAS trial of apalutamide with continued versus intermittent androgen-deprivation therapy (ADT) following prostate-specific antigen (PSA) response in participants with metastatic castration-sensitive prostate cancer (mCSPC) (NCT05884398; CR109327; 56021927PCR3020; EudraCT2022-502686-24-00). The open-label, randomised, prospective study intends to enrol approximately 333 participants in the US, Australia, Brazil, Canada, China, France, Germany and Poland [24] .

In May 2020, Janssen Cilag initiated phase III PRIMORDIUM trial to assess the safety and efficacy of the addition of apalutamide to radiotherapy and an LHRH agonist, in high-risk patients with PSMA-PET-positive hormone-sensitive prostate cancer patients (NCT04557059; EudraCT2019-002957-46; 56021927PCR3015; CR108705). The primary endpoint is time from randomisation until PSMA-PET distant metastatic progression or death from any cause. The randomised, open label trial intends to enrol approximately 412 patients in Australia, Austria, Czech Republic, Denmark, Italy, Lebanon, Poland, Portugal, Russia, Spain, Sweden, Turkey [25] . In September 2021, the trial design details were presented at the 46th European Society for Medical Oncology Congress (ESMO 2021) [26] .

In September 2020, Janssen Research and Development and UNICANCER has resumed the trial [27] . Earlier in March 2020, due to COVID-19 pandemic, Janssen Pharmaceutica and UNICANCER temporarily suspended the phase III CARLHA-2 trial which was designed to compare the efficacy and safety of apatulamide combined with concomitant prostate-bed salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) versus concomitant prostate-bed SRT and ADT in high-risk postprostatectomy biochemically relapsed prostate cancer patients (NCT04181203; EudraCT2017-000155-21; UC-0160/1702). The open-label trial, initiated in January 2020, intended to enrol 490 patients in France [27] .

In August 2020, European Organisation for Research and Treatment of Cancer (EORTC) withdrew a phase III trial that intended to enrol the effect of combination of apalutamide with six months of androgen deprivation therapy by LHRH agonists in patients with prostate cancer, because of extended study timelines and as the additional budget could no longer be supported(NCT03488810; EudraCT2018-000899-15; EORTC-1531-ROG). The randomised, parallel assignment trial was initiated in December 2019, but did not enrol any patients in planned sites Belgium and Spain [28] .

In June 2019, Janssen Research & Development initiated the phase III PROTEUS trial to assess apalutamide in addition to androgen deprivation therapy (ADT) given before and after radical prostatectomy in patients with locally advanced prostate cancer (NCT03767244; EudraCT2018-001746-34; CR108535). The primary endpoint of the trial is to determine the percentage of patients with Pathologic complete response (pCR) and Metastasis-Free Survival (MFS). The randomised, double-blind, placebo-controlled trial intends to enrol approximately 1500 patients in the US, Canada, Germany, the Netherlands, Spain, the UK and may expand to Australia, Brazil, China, Czech Republic, France, Israel, Italy, Japan, South Korea, Poland, Russia and Taiwan [29] .

In December 2023, Aragon Pharmaceuticals completed a phase III open-label expanded access protocol that collected additional safety data until apalutamide is commercially available for participants with non-metastatic castrate-resistant prostate cancer (NM-CRPC) (56021927PCR3010; CR108434; NCT03523338). The open-label trial initiated in July 2018 and enrolled patients in Brazil, Colombia and Mexico [30] .

In May 2020, Janssen Pharmaceutical reported that the phase III SPARTAN trial met all its primary, secondary and exploratory endpoints. Aragon initiated a randomised, double-blind, placebo-controlled phase III SPARTAN trial in August 2013 to investigate the efficacy and safety of apalutamide (JNJ 56021927) in men with high risk, non-metastatic, castration-resistant prostate cancer (EudraCT2012-004322-24; NCT01946204). The trial also includes a sub-study to assess the effect of JNJ 56021927 on ventricular re-polarisation. Recruitment of 1 207 patients was completed in the US, Canada, Australia, New Zealand, the UK, Czech Republic, Austria, Belgium, Germany, Denmark, Japan, Italy, Ireland, France, Finland, Hungary, Netherlands, Romania, Slovakia, Spain, Sweden, Poland, Norway, Israel, Russia, South Korea and Taiwan. Positive results from the trial were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in February 2018. The efficacy data was released by the company in May 2018. In September 2018, the analytical data were published in The Lancet Oncology [31] [32] [33] [34] . In October 2018, Janssen presented results from this trial at the 43rd European Society for Medical Oncology Congress (ESMO-2018) [35] .In May 2019, it was reported that the benefit of apalutamide + ongoing androgen deprivation therapy was maintained in patients with diabetes/hyperglycaemia, cardiovascular disease, hypertension and renal insufficiency. The safety profile of apalutamide was not affected by any comorbidities. In September 2019, Janssen releases the results from a second interim analysis of the SPARTAN trial [36] [37] [38] . In May 2020, the company released final safety and efficacy results from the trial [39] .

Aragon, in November 2015, initiated a phase III ATLAS trial to assess the safety and efficacy of apalutamide in patients with high-risk, localised or locally advanced prostate cancer receiving treatment with primary radiation therapy (ATLAS; NCT02531516; EudraCT2015-003007-38; CR106935; 56021927PCR3003). The primary endpoint is metastasis-free survival, assessed at 72 months. As at June 2022, the randomised, double-blind, placebo-controlled completed enrolment of approximately 1500 patients in the US, Spain, Argentina, Belgium, Brazil, Canada, China, Czech Republic, France, Israel, Germany, South Korea, Malaysia, Mexico, Netherlands, Poland, Romania, Russia, Sweden, Taiwan, Turkey, Ukraine and United Kingdom [40] [41] .

In February 2021, Janssen Pharmaceutical released results and reported that the phase III ACIS tiral met its primary endpoint of radiographic progression-free survival (rPFS. In November 2014, Aragon Pharmaceuticals initiated the phase III ACISstudy to evaluate the safety and efficacy of JNJ 56021927 in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for the treatment of chemotherapy-naive patients with metastatic castration-resistant prostate cancer (CR105505; NCT02257736; EudraCT2014-001718-25; 56021927PCR3001). The randomised, double-blind, parallel-assignment study completed enrolment of 982 patients in the US, Argentina, Australia, Belgium, Brazil, Canada, France, Japan, South Korea, Mexico, the Netherlands, Russia, South Africa, Spain, Germany, Italy and the UK [42] [43] [44] . Later, in June 2021, results from the trial were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021) [45] .

In January 2019, Janssen announced unblinding of the TITAN study following recommendation of the Independent Data Monitoring Committee (IDMC). The trial also met the dual primary endpoints and demonstrated a significant improvement in the radiographic progression-free survival (rPFS) and overall survival (OS). Based on these results, the IDMC recommended that patients in the placebo plus androgen deprivation therapy (ADT) group be given the opportunity to cross over to treatment with apalutamide plus ADT. Patients will be followed for OS and long-term safety as part of the study. In November 2015, Janssen initiated the phase III TITAN trial to determine whether the addition of JNJ 56021927 to ADT provides superior efficacy, compared with ADT alone, in patients with with newly-diagnosed,low-volume metastatic hormone-sensitive prostate cancer (CR107614; 56021927PCR3002; EudraCT2015-000735-32; NCT02489318). The randomised, double-blind trial completed enrolment of 1 052 patients in the US, Brazil, Canada, Spain, Australia, Hungary, Poland, Sweden, Argentina, Czech Republic, France, Israel, Japan, South Korea, Romania, Russia, Turkey, Ukraine, China, Germany, Mexico and the UK, in July 2017. In May 2019, safety and efficacy data from the trial was presented at the 55th Annual Meeting of American Society of Clinical Oncology (ASCO-2019) and simultaneously the data was published in The New England Journal of Medicine. In February 2021, Janssen released four-year final analysis data from the trial. In September 2021, safety and efficacy data from this trial were represented at 46th European Society for Medical Oncology Congress [46] [47] [48] [49] [50] [51] [52] . In June 2022, efficacy data from the trial was presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASC0-2022) [53] . In October 2023, efficacy data from the trial were presented at the 48th European Society for Medical Oncology Congress (ESMO-2023) [54] . In January 2024, updated efficacy data from the statistical extrapolations of the TITAN study presented at the 2024 Genitourinary Cancers Symposium (ASCO-GeCS-2024) [55] .

In March 2017, Janssen Research & Development and Alliance Foundation Trials initiated a phase III PRESTO trial to evaluate the safety and efficacy of apalutamide in combination with degarelix and of apalutamide, abiraterone acetate + prednisone and degarelix [see AdisInsight drug profiles 800005133 and 800016314] in patients with biochemically recurrent prostate cancer (AFT-19; NCT03009981). The open-label, parallel, randomised, three-arm trial enrolled 504 patients in the US [56] . In April 2023, efficacy and safety data from the trial was presented at the 118th Annual Meeting of the American Urological Association (AUA-2023) [57] .

In March 2022, University of California in collaboration with Janssen Scientific Affairs initiated a phase II trial to evaluate the combination of apalutamide and cetrelimab [see AdisInsight profile 800047904] in patients with treatment-emergent small cell neuroendocrine prostate cancer (NCT04926181; 21553; NCI2021-05986). The open-label trial intends to enrol 24 patients in US [58] .

In May 2021, Janssen in collaboration with M.D. Anderson Cancer Center completed a phase II trial that evaluated the combination effect of abiraterone acetate [see AdisInsight drug profile 800005133] and standard of care prednisone to the combination of apalutamide and leuprolide (LHRHa, LHRH agonist) can help to control prostate cancer when given before surgery (2016-0527; NCI-2018-01064; NCT03279250; P30CA016672). The open-label, parallel, randomised trial was initiated in October 2017 and enrolled 86 patients in the US [59] . In January 2019, Patient enrollment was completed. 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) [60] .

In October 2023, Janssen Research & Development completed the phase II trial that evaluated the efficacy of adjuvant treatment of apalutamide in patients with prostate cancer (CR108875; 56021927PCR2041; NCT04523207). The open label, multicenter trial was initiated in August 2020 and enrolled 108 patients in the US. In June 2023, results form this trial were presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [61] [62]

In January 2019, Instituto do Cancer do Estado de Sao Paulo in collaboration with Janssen initiated a phase II trial to evaluate the efficacy and safety neoadjuvant androgen deprivation therapy (ADT) with goserelin and abiraterone [see Adis Insight Drug profile 800005133] with or without apalutamide prior to radical prostatectomy for patients diagnosed with localized high-risk prostate cancer (NP 779/15; NCT02789878). The randomised, single blind study intends to enrol approximately 64 patients in Brazil [63] . In June 2022, data from the trial were presented at 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [64]

In July 2019, Janssen-Cilag and Cambridge University Hospitals NHS Foundation Trust completed a phase II trial that evaluated the safety, tolerability and efficacy of apalutamide, in patients with prostate cancer (TAPS01; NCT03365297; EudraCT2017-001700-29). Evaluation of the physiological response was the defined primary endpoint of the trial. The open label trial was initiated in June 2018 and recruited 11 patients in the UK [65]

NRG Oncology and National Cancer Institute initiated a phase II trial to evaluate the efficacy of radiation therapy with or without apalutamide, in patients with stage III-IV prostate cancer (NCI2017-01268; NRG-GU006; U10CA180868; NCT03371719). Evaluation of the progression free survival is the defined primary endpoint of the trial. The randomised, double-blind trial intends to enrol approximately 324 patients in the US [66] .

In March 2018, M.D. Anderson Cancer Center and Janssen initiated a phase II trial to evaluate the safety of apalutamide for the treatment of prostrate cancer and to understand if administration of apalutamide (ARN 509) prior to prostatectomy reduces the frequency of pathologic features that drives post-operative radiation therapy (2015-0693; NCT03412396). The open label trial is designed to enrol approximately 45 patients in the US [67] . In September 2021, results from the trial was presented at 116th Annual Meeting of the American Urological Association (AUA-2021) [68] .

In February 2021, M.D. Anderson Cancer Center and Janssen suspended a phase II trial of abiraterone acetate [See Adis Insight Drug Profile 800005133] and apalutamide in castration-resistant bone metastatic prostate cancer patients evaluating a predetermined biomarker signature (NCT03360721; 2017-0060). The trial was suspended as per decision of principle investigator. The open-label trial was initiated in March 2018 and was enrolling approximately 60 patients in the US [69] .

In July 2017, Janssen in collaboration with Duke University Medical Center initiated the phase II PANTHER trial to evaluate the efficacy of apalutamide and abiraterone acetate combination in chemotherapy-naïve African American and Caucasian men with metastatic castration resistant prostate cancer (Pro00075097; NCT03098836). The trial intends to enrol 100 patients in the US [70] .

In June 2021, Janssen Pharmaceuticals and Latin American Cooperative Oncology Group completed a phase II trial that assessed the safety and efficacy of androgen deprivation therapy plus abiraterone [see Adis Insight drug profile 800005133], abiraterone plus apalutamide or apalutamide alone in hormone naïve locally advanced or metastatic prostate cancer (LACOG 0415; NCT02867020).The randomised, parallel, open-label trial was initiated in October 2017 and enrolled 128 patients in Brazil [71] . 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) [72] . 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) [73] .

In June 2017, Singapore General Hospital initiated the phase II NEAR trial to evaluate the efficacy of combining neoadjuvant apalutamide with radical prostatectomy (RP), in patients with high risk prostate cancer (ARN509 - 2016; NCT03124433). The open label trial intends to enrol approximately 30 patients in Singapore [74] . In May 2019 and May 2020, results from the trial were presented at the 114th and 115th Annual Meeting of the American Urological Association (AUA-2019) (AUA-2020) respectively [75] [76] .

In February 2017, Institut Paoli Calmettes initiated a phase II trial to evaluate active surveillance, with or without a 6 months apalutamide treatment, in patients with low risk prostate cancer (PC-ARN-IPC2015-025; NCT03088124; EudraCT2016-001266-29). The open-label trial intends to enrol 206 patients in France [77] .

In May 2016, M.D. Anderson Cancer Center initiated the phase II DynaMO (A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer) trial to assess the safety and efficacy of apalutamide 240mg in combination with abiraterone acetate 1 000mg, and prednisone 5mg with either ipilimumab 3 mg/kg or cabazitaxel plus carboplatin 25 mg/m2 [see AdisInsight drug profiles 800005133, 800006680 and 800015344] (2014-0386; NCT02703623). The randomised 1:1:1, parallel, open-label trial will enrol approximately 265 patients in the US [78] .

In May 2016, Janssen Pharmaceuticals, in collaboration with Memorial Sloan Kettering Cancer Center (sponsor) and Weill Medical College of Cornell University, initiated a phase II trial to assess the efficacy of apalutamide, leuprolide and abiraterone with stereotactic, ultra-hypofractionated radiation (AASUR) in very high risk prostate cancer (15-334; c15-164; NCT02772588). The open-label, single-group trial is recruiting 64 patients in the US [79] . In June 2021, results from the trial were presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021) [80] .

In March 2019, Aragon Pharmaceuticals completed a phase II trial that evaluated the role of apalutamide in men with biochemically relapsed hormone sensitive prostate cancer (ARN509-002; NCT01790126). The randomised, open-label trial was initiated in March 2013 and enrolled 90 patients in the US [81] .

In October 2016, Janssen Scientific Affairs and Dana-Farber Cancer Institute initiated a phase II trial to assess the safety and efficacy of apalutamide in combination with abiraterone acetate, prednisone and leuprolide in patients with intermediate-high risk prostate cancer undergoing prostatectomy (16-223; NCT02903368). The randomised, crossover, open-label trial enrolled 118 patients in the US [82] . In March 2021, data from the trial were released by the company [83] . In June 2023, additional data from the trial were presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [84] . In January 2024, clinical data was presented at 2024 Genitourinary Cancers Symposium (ASCO-GSC-2024) [85]

Aragon reported that enrolment of 127 patients with advanced castration-resistant prostate cancer (CRPC) in a phase I/II trial was completed in March 2013 (ARN-509-001; NCT01171898). However, recruitment appears to have resumed since January 2014. The phase I portion selected a tolerable dose for the phase II component, which is enrolling 3 different cohorts of patients: 50 patients with non-metastatic, treatment-naive CRPC, 20 patients with treatment-naive metastatic disease, and 20 patients with metastatic CRPC which has progressed following abiraterone therapy. The trial was initiated in July 2010 in the US. Phase I results showed dose-proportional inhibition of tracer uptake at the 120mg daily dose level and above, consistent with the plasma levels that produced optimal inhibition of tumour growth pre-clinically. Interim results from the phase II component of the trial were presented at the 37th Congress of the European Society of Medical Oncology (ESMO-2012). Based on these results, a proposal to conduct an all-comers registration trial in the post-chemotherapy setting was abandoned in favour of the phase III SPARTAN trial in the NM-CRPC setting [86] [87] [88] [89] .

In December 2019, Janssen and Dana-Farber Cancer Institute terminated a phase II trial due to safety concerns(16-485; NCT03093272). The trial was initiated in June 2017 to evaluate the efficacy of docetaxel in combination with apalutamide in castration-resistant prostate cancer patients post abiraterone acetate. The open-label trial enrolled nine patients, in the US [90] .

In May 2023, Janssen completed a phase II trial that evaluated the efficacy and safety of apalutamide in combination with a gonadotropin-releasing hormone (GnRH) agonist in participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC) (56021927SGT2001; CR108758; NCT04325828). The open-label trial was initiated in April 2020 and enrolled approximately 31 patients in Japan. In June 2022, results from this trial were presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [91] [92] .

In November 2019, Janssen Research & Development initiated a phase I pharmacokinetic trial to characterise the single-dose pharmacokinetics of apalutamide in patients with severe hepatic impairment, as compared with participants with normal hepatic function (NCT04154774; 56021927PCR1026; CR108714). The open label, non-randomized trial intends to enrol approximately 16 volunteers and patients with hepatic impairment, in the US [93] .

In April 2019, Janssen completed a phase I trial that determined the bioavailability of apalutamide tablets administered orally as dispersed tablets mixed in applesauce relative to whole tablets under fasting conditions in healthy male participants, initiated in January 2019 (56021927PCR1024; CR108562; NCT03802682). The open-label, randomised trial is enrolled approximately 12 volunteers in Belgium [94] .

In November 2021, Janssen Research & Development completed a phase Ib trial that evaluated the safety of JNJ 63723283 [see AdisInsight drug profile 800047904] in combination with apalutamide (NCT03551782; CR108476; EudraCT2018-000182-37; 56021927PCR2032). The open-label, non-randomised trial, initiated in June 2018, recruited 33 patients the US, Belgium, Canada, Italy, the Netherlands, Russia and Spain [95] .

In June 2021, the Memorial Sloan-Kettering Cancer Center in collaboration with Aragon Pharmaceuticals completed a phase Ib trial which assessed the safety and efficacy of JNJ 56021927 plus everolimus in patients with progressive, metastatic, castration-resistant prostate cancer after treatment with abiraterone acetate (13-025; NCT02106507). The open-label trial was initiated in April 2014 and enrolled nine patients in the US [96] .

In August 2018, Janssen initiated a phase I trial to evaluate the pharmacokinetic following a single dose and multiple dose treatment and the safety of apalutamide, in patients with metastatic castration resistant prostate cancer (56021927PCR1013; CR107444; NCT03523442). The open label trial intends to enrol approximately 17 patients in China [97] .

In July 2019, Janssen Research & Development completed the phase I BEDIVERE trial that assessed the safety and pharmacokinetics of niraparib plus apalutamide, in patients with metastatic castration resistant prostate cancer, who may or may not have deoxyribonucleic acid-repair anomalies (CR108230; EudracT2016-002694-35; 64091742PCR1001; NCT02924766). The open-label, single-group trial was initiated in October 2016, and enrolled 34 patients in the US and Canada [98] .

Aragon Pharmaceuticals completed the phase I trial which evaluate the effect of multiple dose of apalutamide (JNJ-56021927) on the pharmacokinetics of multiple cytochrome P450 and transporter substrates in patients with castration resistant prostate cancer (NCT02592317; CR108072; EudraCT2015-003691-72). The open label trial was initiated in February 2016 and enrolled 23 patients in Moldova and Spain [99] .

In October 2022, Aragon completed the phase Ib trial to assess the effect of daily treatment with JNJ 56021927 on QT/QTc interval in patients with castration resistant prostate cancer (56021927PCR1019; 2015-004044-19; CR108049; NCT02578797). This open-label trial was initiated in December 2015 and enrolled 45 patients in the US, Canada, Netherlands, Moldova and the UK [100] .

Aragon initiated a single-arm phase I trial in July 2014 to investigate the potential drug-drug interaction between JNJ 56021927 and abiraterone acetate in men with metastatic, castration-resistant prostate cancer (NCT02123758; EudraCT2014-001426-14). The trial will also assess safety and efficacy. The trial will enrol 26 patients, initially in the US and Canada, and later in the EU [101] .

Aragon initiated a phase I trial in March 2013 to investigate the absolute bioavailability and microtracer absorption, metabolism and excretion of 14C-labelled JNJ 56021927 in healthy male volunteers (NCT01822041). The trial enrolled 12 subjects in the Netherlands.

In June 2014, Janssen initiated a single-arm phase I trial to investigate the safety and tolerability of JNJ 56021927 in Japanese patients with metastatic, castration-resistant prostate cancer (NCT02162836). The trial enrolled six patients in Japan, and it was completed in May 2019 [102] .

Aragon initiated a phase Ib clinical trial assessing JNJ 56021927 in combination with abiraterone acetate and prednisone in patients with metastatic CRPC in February 2013 (ARN509-004; NCT1792687). The open-label trial will enrol approximately 21 patients in the US. The primary endpoint is to determine the maximum tolerated dose/recommended phase II dose of JNJ 56021927 when administered in combination with abiraterone acetate. The trial will also evaluate the safety, tolerability and preliminary anti-tumour activity of the combination [103] .

A phase Ib study is planned of JNJ 56021927 in combination with everolimus in patients with progressive metastatic CRPC after treatment with abiraterone acetate.

In February 2017, Janssen Research and Development completed a phase I trial that evaluated the pharmacokinetics of apalutamide in participants with mild to moderate hepatic impairment compared with participants with normal hepatic function (CR107774; 56021927PCR1018; NCT02524717). The open-label, single-group assignment trial, initiated in August 2015, enrolled 24 participants (≥18 years and ≤80 years) in the US, who were monitored for pharmacokinetics and safety during the three phases of the trial namely, the screening phase (21 days), open-label treatment phase (8 days) and a follow-up phase, accounting for a total of 78 day trial [104] .

In December 2016, Janssen Pharmaceutical completed a phase I trial assessed pharmacokinetics, safety and tolerability of apalutamide (60mg, 120mg and 240mg) tablet and its active metabolite JNJ 56142060 in healthy volunteers (CR108165; 56021927PCR1021; NCT02835508). The single-dose, open-label trial initiated in June 2016, enrolled 18 volunteers in Japan [105] .

In December 2014, Janssen completed a phase I drug-drug interaction trial to assess the effect of multiple doses of itraconazole or gemfibrozil on the pharmacokinetics of JNJ 56021927 and its metabolites in healthy male volunteers (56021927PCR1012; CR105398; NCT02230033). This randomised, parallel-assignment, open-label trial was initiated in September 2014 and enrolled 45 volunteers in the US [106] .

In April 2014, Janssen completed a phase I trial, which assessed the relative bioavailability of single doses of tablet and capsule formulations of JNJ 56021927 in healthy male participants (NCT02031666). The randomised, open-label trial was initiated in December 2013 and enrolled 120 subjects in the US [107] . Janssen completed another phase I trial of JNJ 56021927 in November 2014, that compared the relative bioavailability of three tablet formulations of JNJ 56021927 with the capsule formulation under fasted conditions in healthy male volunteers (NCT02160756). This randomised, open-label trial was initiated in July 2014 and enrolled 75 volunteers in the US [108] .

In December 2016, Janssen Scientific Affairs and Weill Medical College of Cornell University initiated a phase I trial to assess the safety and efficacy of apalutamide in combination with abiraterone acetate, docetaxel and prednisone in patients with metastatic CRPC (1509016578; NCT02913196). The open-label, single-group trial is recruiting 24 patients in the US. During the trial, RECIST response was showed in 5 patients. In March 2019, data was presented at the 110th Annual Meeting of the American Association for Cancer Research (AACR-2019) [109] [110] .

Other investigator-sponsored trials

In November 2017, Dana-Farber Cancer Institute, in collaboration with Janssen, initiated the phase II FORMULA-509 trial to evaluate combination of salvage radiation therapy and androgen deprivation therapy with or without abiraterone acetate and apalutamide (NCT03141671; 16-623). The randomised, open-label trial intends to enrol approximately 190 patients in the US [111] .

In October 2016, Case Comprehensive Cancer Center initiated a phase II trial to assess the safety and efficacy of neoadjuvant combination therapy of leuprolide [see AdisInsight drug profile 800009297] and apalutamide in patients with prostate cancer undergoing radical prostatectomy (CASE5815; NCT02770391). The primary endpoint is to evaluate the differential effect of neoadjuvant leuprolide and apalutamide on dihydrotestosterone concentration in benign prostate tissue based on HSD3B1 genotype. The single-group, open-label trial is enrolling 57 patients in the US [112] .

In January 2022, University of Washington, in collaboration with the National Cancer Institute and Janssen terminated a phase II trial of apalutamide, due to slow accrual, in patients with prostate cancer who are in active surveillance (NCI-2016-00221; 9582; P30CA015704; NCT02721979). The open-label, single-group trial initiated in November 2017, enrolled 24 patients in the US [113] .

In December 2020, University of Washington, in collaboration with the National Cancer Institute and Janssen completed a phase II trial that evaluated the efficacy of apalutamide, abiraterone acetate, prednisone, degarelix and indomethacin in patients with localised prostate cancer, prior to prostatectomy (NCI-2016-01027; 9628; P30CA015704; NCT02849990). The open-label, single-group trial was initiated in March 2017, and enrolled 22 patients in the US [114] .

Financial information

In April 2010, Aragon secured $US22 million in Series B financing. These funds were to be used to support a phase I trial of JNJ 56021927 in the treatment of castration-resistant prostate cancer, and allow it to continue into phase II trials [115] . Series C financing in March 2012 secured $US42 million for the advancement of Aragon Pharmaceuticals pipeline, including JNJ 56021927, for hormone-driven cancers [87] .

Patent Information

Patent disputes

In May 2022, Aragon Pharmaceuticals, Inc. and Janssen Biotech, Inc. (collectively, Janssen) and Sloan Kettering Institute for Cancer Research (SKI) initiated patent infringement lawsuits in United States District Court for the Districts of New Jersey and Delaware against Lupin Limited and Lupin Pharmaceuticals, Inc. (collectively, Lupin), which filed an ANDA seeking approval to market a generic version of ERLEADA before the expiration of U.S. Patent No. 9 481 663 (’663). In August 2022, Janssen and SKI filed a first amended complaint against Lupin adding U.S. Patent Nos. 9 884 054 (’054), 10 052 314 (’314), 10 702 508 (’508) and 10 849 888 (’888) to the suit. Janssen and SKI are seeking an order enjoining Lupin from marketing its generic version of ERLEADA before the expiration of the ’663, ’054, ’314, ’508, and ’888 patents. In August 2022, Janssen and SKI voluntarily dismissed the Delaware complaint. The New Jersey action is proceeding. In May 2022, Janssen and SKI initiated a patent infringement lawsuit in United States District Court for the District of New Jersey against Zydus Worldwide DMCC, Zydus Pharmaceuticals (USA), Inc., and Zydus Lifesciences Limited (collectively, Zydus), which filed an ANDA seeking approval to market a generic version of ERLEADA before the expiration of the ’663, ’054, ’314, ’508, and ’888 patents. Janssen and SKI are seeking an order enjoining Zydus from marketing its generic version of ERLEADA before the expiration of the ’663, ’054, ’314, ’508, and ’888 patents. In May 2022, Janssen, The Regents of the University of California (UC), and SKI initiated patent infringement lawsuits in United States District Court for the Districts of New Jersey and Delaware against Sandoz Inc. (Sandoz), which filed an ANDA seeking approval to market a generic version of ERLEADA before the expiration of the ’663 patent and U.S. Patent Nos. 8 445 507 (’507), 8 802 689 (’689), 9 338 159 (’159), and 9 987 261 (’261). In August 2022, Janssen, UC, and SKI filed a first amended complaint against Sandoz adding the ’054, ’314, ’508, and ’888 patents to the suit. In August 2022, Janssen, UC, and SKI voluntarily dismissed the Delaware complaint. In December 2022, Janssen, UC, and SKI filed a second amended complaint against Sandoz withdrawing the ’054, ’314, ’508, and ’888 patents from the suit without prejudice. Janssen, UC, and SKI are seeking an order enjoining Sandoz from marketing its generic version of ERLEADA before the expiration of the ’663, ’507, ’689, ’159, and ’261 patents. The New Jersey action is proceeding.
In May 2022, Janssen, UC, and SKI initiated patent infringement lawsuits in United States District Court for the Districts of New Jersey and Delaware against Eugia Pharma Specialities Limited, Aurobindo Pharma USA, Inc., and Auromedics Pharma LLC (collectively, Eugia), which filed an ANDA seeking approval to market a generic version of ERLEADA before the expiration of the ’663, ’507, ’689, ’159 and ’261 patents. In September 2022, Janssen, UC, and SKI filed a first amended complaint against Eugia adding U.S. Patent Nos. 9 884 054 (’054), 10 052 314 (’314), 10 702 508 (’508) and 10,849,888 (’888) to the suit. In September 2022, Janssen, UC, and SKI voluntarily dismissed the Delaware complaint. Janssen, UC, and SKI are seeking an order enjoining Eugia from marketing its generic version of ERLEADA before the expiration of the ’663,’507, ’689, ’159, ’261, ’054, ’314, ’508, and ’888 patents. The New Jersey action is proceeding. In May 2022, Janssen, UC, and SKI initiated patent infringement lawsuits in United States District Court for the Districts of New Jersey and Delaware against Hetero Labs Limited Unit V and Hetero USA, Inc. (collectively, Hetero), which filed an ANDA seeking approval to market a generic version of ERLEADA before the expiration of the ’663, ’507,’054, ’314,’508, and ’888 patents. Janssen, UC, and SKI are seeking an order enjoining Hetero from marketing its generic version of ERLEADA before the expiration of the ’663, ’507, ’054, ’314, ’508 and ’888 patents [116] .

In August 2022, Janssen, UC, and SKI voluntarily dismissed the Delaware complaint. The New Jersey action is proceeding.

Drug Properties & Chemical Synopsis

  • Route of administration PO
  • Formulation Capsule, Tablet, unspecified
  • Class Antiandrogens, Antineoplastics, Aza compounds, Benzamides, Pyridines, Small molecules, Spiro compounds, Sulfhydryl compounds, Thiohydantoins
  • Target Androgen receptor
  • Mechanism of Action Androgen receptor antagonists
  • WHO ATC code

    L02B-B05 (Apalutamide)

  • EPhMRA code

    L2B2 (Cytostatic anti-androgens)

  • Chemical name 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6- thioxo-5,7-diazaspiro(3.4)octan-5-yl)-2-fluoro-N- methylbenzamide
  • Molecular formula C21 H15 F4 N5 O2 S
  • SMILES C(C1C(=CC(=CC=1)N1C2(CCC2)C(N(C1=S)C1C=NC(=C(C=1)C(F)(F)F)C#N)=O)F)(=O)NC
  • Chemical Structure
  • CAS Registry Number 956104-40-8

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

adenocarcinoma

Arm Group Label

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

Androgen Receptor (AR)

1

1

1

1

adenocarcinoma

Outcome Measure

zinc finger homeobox 3

zinc finger and BTB domain containing 16

XPF

XPD

transmembrane protease, serine 2

Testosterone

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1

SPINK1

speckle-type POZ protein

SERPINA2

RUNX1

RING1 and YY1 binding protein

ring finger protein 43

retinoblastoma 1

RAD51 paralog C

RAD51 paralog B

RAC-alpha serine/threonine-protein kinase (AKT)

PTEN

PSA

pS6K

PIK3R1

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

partner and localizer of BRCA2

p53 (tumor protein p53)

p16

nuclear receptor coactivator 2

Nuclear protein Ki67

NK3 homeobox 1

NFE2L2

MSH6

MSH2

MLH1

methylmalonic aciduria (cobalamin deficiency) cblB type

mediator complex subunit 12

MDM4, p53 regulator

MDM2

lysine (K)-specific methyltransferase 2D

lysine (K)-specific methyltransferase 2C

lysine (K)-specific demethylase 6A

KRAS

IDH2

IDH1

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

GR

GNAS complex locus

GINS complex subunit 2

FOXA1

forkhead box P1

folate hydrolase (prostate-specific membrane antigen) 1

Fanconi anemia, complementation group G

Fanconi anemia, complementation group F

Fanconi anemia, complementation group E

Fanconi anemia, complementation group D2

FANCC

FANCA

F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase

excision repair cross-complementation group 5

excision repair cross-complementation group 3

Estradiol-17beta 3-sulfate

ERCC1

endoplasmic reticulum lectin 1

Dihydrotestosterone

CYP17

Cyclin-dependent kinase 4 (CDK4)

cyclin-dependent kinase 12

Cyclin D1

cullin 1

Clusterin

chromodomain helicase DNA binding protein 1

CDKN1B

CDK6

CD56

Caspase-3 (CASP3)

c-Myc

BRCA2

BRCA1

BRAF

Beta-catenin

ATR

Ataxia telangiectasia mutated

ASXL1

ARID1A

anthrax toxin receptor 1

Androgen Receptor (AR)

Alkaline phosphatase (ALPL)

AKT3

AKT2

Adenomatous polyposis coli protein (APC)

4E-BP1

1

1

1

1

1

10

1

1

1

1

2

1

1

1

1

1

1

1

2

2

44

1

1

1

2

1

2

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

2

1

2

1

1

1

1

1

1

1

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

2

1

1

1

1

1

adenocarcinoma

Brief Title

Testosterone

PSA

gonadotropin releasing hormone 1

folate hydrolase (prostate-specific membrane antigen) 1

cytochrome P450 family 2 subfamily B member 6

Androgen Receptor (AR)

1

1

3

1

1

2

adenocarcinoma

Arm Group Description

PSA

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

4

3

3

1

adenocarcinoma

Detailed Description

UBE2C

transmembrane protease, serine 2

Testosterone

PSA

peptidylprolyl isomerase G

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

gonadotropin releasing hormone 1

folate hydrolase (prostate-specific membrane antigen) 1

FK506 binding protein 5

EZH2

endoplasmic reticulum lectin 1

Dihydrotestosterone

dicer 1, ribonuclease type III

Dehydroepiandrosterone

cytochrome P450 family 2 subfamily C member 8

CYP3A4

CYP2C9

CYP2C19

Caspase-3 (CASP3)

Androsterone

Androstenedione

Androstanedione

Androstanediol

Androgen Receptor (AR)

5-Androstenediol

1

1

8

19

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

adenocarcinoma

Eligibility Criteria

Thyroid stimulating hormone beta (TSH)

Testosterone

T-cell surface antigen CD4

synaptophysin

ribulose-5-phosphate-3-epimerase

retinoblastoma 1

PTEN

PSA

p53 (tumor protein p53)

Nuclear protein Ki67

neural proliferation, differentiation and control 1

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

endoplasmic reticulum lectin 1

dicer 1, ribonuclease type III

cytotoxic T-lymphocyte-associated protein 4

cytochrome P450 family 2 subfamily C member 8

cytochrome P450 family 2 subfamily B member 6

CYP3A4

CYP2C9

CYP2C19

Creatinine

CD56

AR-V7

Androgen Receptor (AR)

ALT

1

32

2

1

1

1

1

46

1

1

1

5

6

4

1

1

1

1

3

1

1

1

2

1

1

2

1

adenocarcinoma

Official Title

Testosterone

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

cytochrome P450 family 2 subfamily B member 6

Androgen Receptor (AR)

1

1

3

1

2

1

3

adenocarcinoma

Brief Summary

Testosterone

PSA

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

4

10

1

1

1

bone metastases

Detailed Description

PSA

1

bone metastases

Eligibility Criteria

Testosterone

PTEN

PSA

p53 (tumor protein p53)

Nuclear protein Ki67

Gonadotropin releasing hormone

CD56

AR-V7

Androgen Receptor (AR)

1

1

1

1

1

1

1

1

1

bone metastases

Outcome Measure

PSA

1

cancer metastases

Detailed Description

Testosterone

PSA

folate hydrolase (prostate-specific membrane antigen) 1

1

1

1

cancer metastases

Eligibility Criteria

Testosterone

T-cell surface antigen CD4

PSA

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

2

1

1

1

1

1

cancer metastases

Outcome Measure

Testosterone

PSA

1

2

carcinoma

Arm Group Label

Gonadotropin releasing hormone

1

carcinoma

Outcome Measure

Thyroid stimulating hormone beta (TSH)

Testosterone

PSA

Leptin

folate hydrolase (prostate-specific membrane antigen) 1

C-peptide

24,25-Dihydroxyvitamin D

1

1

3

1

1

1

1

carcinoma

Brief Title

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

carcinoma

Arm Group Description

Gonadotropin releasing hormone

1

carcinoma

Detailed Description

Testosterone

PSA

folate hydrolase (prostate-specific membrane antigen) 1

1

3

1

carcinoma

Eligibility Criteria

Thyroid stimulating hormone beta (TSH)

Testosterone

sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)

PSA

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

cytochrome P450 family 2 subfamily B member 6

Androgen Receptor (AR)

1

3

1

4

1

1

1

1

carcinoma

Official Title

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

carcinoma

Brief Summary

sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)

PSA

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

1

1

neuroendocrine carcinoma

Detailed Description

PSA

1

neuroendocrine carcinoma

Eligibility Criteria

Testosterone

synaptophysin

retinoblastoma 1

PSA

1

1

1

1

neuroendocrine carcinoma

Outcome Measure

PSA

1

prostate cancer

Arm Group Label

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

Androgen Receptor (AR)

2

2

1

1

prostate cancer

Outcome Measure

zinc finger homeobox 3

zinc finger and BTB domain containing 16

XPF

XPD

transmembrane protease, serine 2

Thyroid stimulating hormone beta (TSH)

Testosterone

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1

SPINK1

speckle-type POZ protein

SERPINA2

RUNX1

RING1 and YY1 binding protein

ring finger protein 43

retinoblastoma 1

RAD51 paralog C

RAD51 paralog B

RAC-alpha serine/threonine-protein kinase (AKT)

PTEN

PSA

pS6K

progesterone receptor membrane component 1

PIK3R1

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

partner and localizer of BRCA2

p53 (tumor protein p53)

p16

nuclear receptor coactivator 2

Nuclear protein Ki67

NK3 homeobox 1

NFE2L2

MSH6

MSH2

MLH1

methylmalonic aciduria (cobalamin deficiency) cblB type

mediator complex subunit 12

MDM4, p53 regulator

MDM2

lysine (K)-specific methyltransferase 2D

lysine (K)-specific methyltransferase 2C

lysine (K)-specific demethylase 6A

Leptin

KRAS

IDH2

IDH1

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

GR

GNAS complex locus

GINS complex subunit 2

FOXA1

forkhead box P1

folate hydrolase (prostate-specific membrane antigen) 1

Fanconi anemia, complementation group G

Fanconi anemia, complementation group F

Fanconi anemia, complementation group E

Fanconi anemia, complementation group D2

FANCC

FANCA

F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase

excision repair cross-complementation group 5

excision repair cross-complementation group 3

Estradiol-17beta 3-sulfate

ERCC1

endoplasmic reticulum lectin 1

Dihydrotestosterone

CYP17

Cyclin-dependent kinase 4 (CDK4)

cyclin-dependent kinase 12

Cyclin D1

cullin 1

Clusterin

chromodomain helicase DNA binding protein 1

CDKN1B

CDK6

CD56

Caspase-3 (CASP3)

C-peptide

c-Myc

BRCA2

BRCA1

BRAF

Beta-catenin

ATR

Ataxia telangiectasia mutated

ASXL1

ARID1A

anthrax toxin receptor 1

Androgen Receptor (AR)

Alkaline phosphatase (ALPL)

AKT3

AKT2

Adenomatous polyposis coli protein (APC)

4E-BP1

24,25-Dihydroxyvitamin D

1

1

1

1

1

1

14

1

1

1

1

2

1

1

1

1

1

1

1

2

2

54

1

3

1

1

2

1

2

1

2

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

2

1

3

1

1

1

1

1

1

1

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

2

1

1

1

1

1

1

prostate cancer

Brief Title

Testosterone

PSA

gonadotropin releasing hormone 1

folate hydrolase (prostate-specific membrane antigen) 1

cytochrome P450 family 2 subfamily B member 6

Androgen Receptor (AR)

1

1

3

1

1

3

prostate cancer

Arm Group Description

PSA

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

5

4

5

1

prostate cancer

Detailed Description

UBE2C

transmembrane protease, serine 2

Testosterone

speckle-type POZ protein

SERPINF2

PTEN

PSA

peptidylprolyl isomerase G

PARP-1

p53 (tumor protein p53)

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

gonadotropin releasing hormone 1

folate hydrolase (prostate-specific membrane antigen) 1

FK506 binding protein 5

EZH2

ERG

endoplasmic reticulum lectin 1

Dihydrotestosterone

dicer 1, ribonuclease type III

Dehydroepiandrosterone

cytochrome P450 family 2 subfamily C member 8

CYP3A4

CYP2C9

CYP2C19

cyclin-dependent kinase 12

collagen, type XI, alpha 2

chromodomain helicase DNA binding protein 1

Caspase-3 (CASP3)

BRCA2

Ataxia telangiectasia mutated

Androsterone

Androstenedione

Androstanedione

Androstanediol

Androgen Receptor (AR)

Adenosine diphosphate ribose

5-Androstenediol

1

1

9

1

1

1

22

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

prostate cancer

Eligibility Criteria

tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)

Thyroid stimulating hormone beta (TSH)

Testosterone

T-cell surface antigen CD4

synaptophysin

ribulose-5-phosphate-3-epimerase

retinoblastoma 1

PTEN

PSA

p53 (tumor protein p53)

Nuclear protein Ki67

neural proliferation, differentiation and control 1

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

endoplasmic reticulum lectin 1

DNA (cytosine-5-)-methyltransferase 3 beta

dicer 1, ribonuclease type III

cytotoxic T-lymphocyte-associated protein 4

cytochrome P450 family 2 subfamily C member 8

cytochrome P450 family 2 subfamily B member 6

CYP3A4

CYP2C9

CYP2C19

Creatinine

CD56

AR-V7

Androgen Receptor (AR)

ALT

1

4

41

2

1

1

1

1

58

1

1

1

6

7

6

1

1

1

1

1

3

1

1

1

3

1

1

3

1

prostate cancer

Official Title

Testosterone

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

folate hydrolase (prostate-specific membrane antigen) 1

cytochrome P450 family 2 subfamily B member 6

Androgen Receptor (AR)

1

1

3

1

2

1

4

prostate cancer

Brief Summary

Testosterone

PSA

gonadotropin releasing hormone 1

Gonadotropin releasing hormone

glutamyl aminopeptidase

folate hydrolase (prostate-specific membrane antigen) 1

4

13

1

2

1

1

salivary gland cancer

Arm Group Label

Gonadotropin releasing hormone

1

salivary gland cancer

Outcome Measure

progesterone receptor membrane component 1

1

salivary gland cancer

Brief Title

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

salivary gland cancer

Arm Group Description

Gonadotropin releasing hormone

1

salivary gland cancer

Eligibility Criteria

tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)

Thyroid stimulating hormone beta (TSH)

Testosterone

sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)

Creatinine

Androgen Receptor (AR)

1

1

1

1

1

1

salivary gland cancer

Official Title

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

salivary gland cancer

Brief Summary

sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)

Gonadotropin releasing hormone

Androgen Receptor (AR)

1

1

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Apalutamide - Janssen Research and Development 24,25-Dihydroxyvitamin D Outcome Measure
4E-BP1 Outcome Measure
5-Androstenediol Detailed Description
ACTR1A Arm Group Description, Arm Group Label
Adenomatous polyposis coli protein (APC) Outcome Measure
Adenosine diphosphate ribose Detailed Description
ADP-ribosylation factor related protein 1 Arm Group Description, Arm Group Label
AKT2 Outcome Measure
AKT3 Outcome Measure
aldo-keto reductase family 1, member C4 Eligibility Criteria
Alkaline phosphatase (ALPL) Outcome Measure
ALT Eligibility Criteria
Androgen Receptor (AR) Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
Androstanediol Detailed Description
Androstanedione Detailed Description
Androstenedione Detailed Description
Androsterone Detailed Description
ANGPTL1 Arm Group Description, Arm Group Label
anthrax toxin receptor 1 Outcome Measure
apolipoprotein B mRNA editing enzyme catalytic subunit 2 Arm Group Description, Arm Group Label
AR-V7 Eligibility Criteria
ARID1A Outcome Measure
ASXL1 Outcome Measure
Ataxia telangiectasia mutated Detailed Description, Outcome Measure
ATR Outcome Measure
Beta-catenin Outcome Measure
BRAF Detailed Description, Eligibility Criteria, Outcome Measure
BRCA1 Outcome Measure
BRCA2 Detailed Description, Outcome Measure
c-Myc Outcome Measure
C-peptide Outcome Measure
CA125 ovarian cancer antigen (MUC16) Eligibility Criteria
Caspase-3 (CASP3) Detailed Description, Outcome Measure
CD56 Eligibility Criteria, Outcome Measure
CDK6 Outcome Measure
CDKN1B Outcome Measure
chromodomain helicase DNA binding protein 1 Detailed Description, Outcome Measure
Clusterin Outcome Measure
collagen, type XI, alpha 2 Detailed Description, Eligibility Criteria
Creatinine Eligibility Criteria
cullin 1 Outcome Measure
Cyclin D1 Outcome Measure
cyclin-dependent kinase 12 Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
Cyclin-dependent kinase 4 (CDK4) Outcome Measure
CYP17 Outcome Measure
CYP2C19 Detailed Description, Eligibility Criteria
CYP2C9 Detailed Description, Eligibility Criteria
CYP3A4 Detailed Description, Eligibility Criteria
cytochrome P450 family 2 subfamily B member 6 Brief Title, Eligibility Criteria, Official Title
cytochrome P450 family 2 subfamily C member 8 Detailed Description, Eligibility Criteria
cytotoxic T-lymphocyte-associated protein 4 Eligibility Criteria
D-threo-Isocitric acid Arm Group Description
Dehydroepiandrosterone Detailed Description
dicer 1, ribonuclease type III Detailed Description, Eligibility Criteria
Dihydrotestosterone Detailed Description, Outcome Measure
DNA (cytosine-5-)-methyltransferase 3 beta Eligibility Criteria
endoplasmic reticulum lectin 1 Detailed Description, Eligibility Criteria, Outcome Measure
Epidermal growth factor receptor (EGFR) Arm Group Description, Eligibility Criteria
ERCC1 Outcome Measure
ERG Detailed Description
Estradiol-17beta 3-sulfate Outcome Measure
Estrogen receptor alpha (ER alpha) Eligibility Criteria
excision repair cross-complementation group 3 Outcome Measure
excision repair cross-complementation group 5 Outcome Measure
EZH2 Detailed Description
F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase Outcome Measure
FANCA Outcome Measure
FANCC Outcome Measure
Fanconi anemia, complementation group D2 Outcome Measure
Fanconi anemia, complementation group E Outcome Measure
Fanconi anemia, complementation group F Outcome Measure
Fanconi anemia, complementation group G Outcome Measure
FK506 binding protein 5 Detailed Description
folate hydrolase (prostate-specific membrane antigen) 1 Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
forkhead box P1 Outcome Measure
FOXA1 Outcome Measure
GINS complex subunit 2 Outcome Measure
glutamyl aminopeptidase Brief Summary
GNAS complex locus Outcome Measure
Gonadotropin releasing hormone Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title
gonadotropin releasing hormone 1 Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title
GR Outcome Measure
Heptanoic acid Arm Group Description
HER2/ERBB2 Eligibility Criteria
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 Detailed Description, Official Title, Outcome Measure
IDH1 Outcome Measure
IDH2 Outcome Measure
Insulin Eligibility Criteria
KRAS Outcome Measure
L-Aspartic acid Eligibility Criteria
L-Serine Arm Group Description
L-Threonine Arm Group Description
Leptin Outcome Measure
lysine (K)-specific demethylase 6A Outcome Measure
lysine (K)-specific methyltransferase 2C Outcome Measure
lysine (K)-specific methyltransferase 2D Outcome Measure
MAMLD1 Eligibility Criteria
mannose receptor, C type 1 Eligibility Criteria
MAP kinase interacting serine/threonine kinase 1 Arm Group Description
MAP kinase interacting serine/threonine kinase 2 Arm Group Description
MDM2 Outcome Measure
MDM4, p53 regulator Outcome Measure
mediator complex subunit 12 Outcome Measure
methylmalonic aciduria (cobalamin deficiency) cblB type Outcome Measure
Microsatellite Instable (MSI) Eligibility Criteria
MLH1 Eligibility Criteria, Outcome Measure
MLH3 Eligibility Criteria
MSH2 Eligibility Criteria, Outcome Measure
MSH6 Eligibility Criteria, Outcome Measure
neural proliferation, differentiation and control 1 Eligibility Criteria
NFE2L2 Outcome Measure
NK3 homeobox 1 Outcome Measure
Nuclear protein Ki67 Eligibility Criteria, Outcome Measure
nuclear receptor coactivator 2 Outcome Measure
nuclear receptor subfamily 2, group F, member 2 Arm Group Description, Arm Group Label
p16 Outcome Measure
p53 (tumor protein p53) Arm Group Description, Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
PARP-1 Detailed Description, Eligibility Criteria
partner and localizer of BRCA2 Outcome Measure
PD-1/CD279 Outcome Measure
PD-L1/CD274 Arm Group Description, Outcome Measure
peptidylprolyl isomerase G Detailed Description
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta Eligibility Criteria, Outcome Measure
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma Eligibility Criteria, Outcome Measure
PIK3CA Eligibility Criteria, Outcome Measure
PIK3CD Eligibility Criteria, Outcome Measure
PIK3R1 Outcome Measure
PITX2 Arm Group Description, Arm Group Label
PMS1 Eligibility Criteria
PMS2 Eligibility Criteria
Progesterone Eligibility Criteria
progesterone receptor membrane component 1 Outcome Measure
pS6K Outcome Measure
PSA Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Outcome Measure
PTEN Arm Group Description, Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
RAC-alpha serine/threonine-protein kinase (AKT) Eligibility Criteria, Outcome Measure
RAD51 paralog B Outcome Measure
RAD51 paralog C Outcome Measure
retinoblastoma 1 Brief Summary, Eligibility Criteria, Outcome Measure
ribulose-5-phosphate-3-epimerase Eligibility Criteria
ring finger protein 43 Outcome Measure
RING1 and YY1 binding protein Outcome Measure
RNA polymerase III subunit K Eligibility Criteria
RUNX1 Outcome Measure
sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) Brief Summary, Eligibility Criteria
SERPINA2 Outcome Measure
SERPINF2 Detailed Description
speckle-type POZ protein Detailed Description, Outcome Measure
SPINK1 Outcome Measure
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1 Outcome Measure
synaptophysin Eligibility Criteria
T-Cell differentiation antigen CD8 Outcome Measure
T-cell surface antigen CD4 Eligibility Criteria, Outcome Measure
Testosterone Arm Group Description, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
Thyroid stimulating hormone beta (TSH) Eligibility Criteria, Outcome Measure
tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor) Eligibility Criteria
transmembrane protease, serine 2 Detailed Description, Outcome Measure
UBE2C Detailed Description
VEGFR Arm Group Description
XPD Outcome Measure
XPF Outcome Measure
zinc finger and BTB domain containing 16 Outcome Measure
zinc finger homeobox 3 Outcome Measure
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Prostate cancer non-metastatic, castration-resistant prostate cancer Hormone refractory Marketed USA PO / Tablet Janssen Research & Development 03 Apr 2023
Prostate cancer along with Androgen Deprivation Therapy (ADT) in metastatic castration-sensitive prostate cancer patients Adjunctive treatment, Metastatic disease Marketed USA PO / Tablet Janssen Research & Development 03 Apr 2023
Prostate cancer concurrently receiving a gonadotropin-releasing hormone (GnRH) analogue Adjunctive treatment, Hormone refractory Registered Argentina, Australia, Brazil PO / Tablet Janssen Research & Development 16 Nov 2018
Prostate cancer along with Androgen Deprivation Therapy (ADT), in patients with relapsed/refractory or newly diagnosed prostate cancer Adjunctive treatment, Metastatic disease Registered Canada PO / Tablet Janssen Research & Development 13 Dec 2019
Prostate cancer Hormone-sensitive, in combination with androgen deprivation therapy Adjunctive treatment, Metastatic disease Registered European Union, Iceland, Liechtenstein, Norway PO / unspecified Janssen Research & Development 30 Jan 2020
Prostate cancer - Hormone refractory Registered Canada, European Union, Iceland, Liechtenstein, Norway PO / Tablet Janssen Research & Development 17 Jan 2019
Prostate cancer Hormone-sensitive Metastatic disease Registered Japan PO / Tablet Janssen Research & Development 29 May 2020
Prostate cancer - Hormone refractory Preregistration Japan PO / Capsule Janssen Research & Development 28 Mar 2018
Prostate cancer - Combination therapy, First-line therapy, Hormone refractory, Metastatic disease Phase III Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Italy, Japan, Mexico, Netherlands, Russia, South Africa, South Korea, Spain, USA, United Kingdom PO / Capsule Janssen Research & Development 02 Apr 2015
Prostate cancer - Combination therapy, Metastatic disease Phase III Australia, Brazil, Canada, China, France, Germany, Poland, USA PO / unspecified Janssen Research & Development 31 Aug 2023
Prostate cancer - Combination therapy, First-line therapy, Late-stage disease, Metastatic disease Phase III Brazil PO / Tablet Janssen Research & Development 30 Nov 2016
Prostate cancer along with androgen deprivation therapy (ADT), before and after radical prostatectomy Adjunctive treatment, Late-stage disease, Neoadjuvant therapy Phase III Canada, Germany, Netherlands, Spain, USA, United Kingdom PO / Tablet Janssen Research & Development 11 Jun 2019
Prostate cancer - Adjunctive treatment, Hormone refractory Phase III Colombia, Mexico PO / Tablet Janssen Research & Development 03 Jul 2018
Prostate cancer - Combination therapy, Second-line therapy or greater Phase III USA PO / Tablet Janssen Research & Development 06 Mar 2017
Prostate cancer - Hormone refractory Phase III Australia, Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Russia, Slovakia, South Korea, Spain, Sweden, Taiwan, United Kingdom PO / Capsule Janssen Research & Development 16 Jun 2014
Prostate cancer along with Androgen Deprivation Therapy (ADT) Adjunctive treatment, Metastatic disease, Newly diagnosed Phase III Brazil, Czech Republic, France, Hungary, Israel, Japan, Poland, Romania, Russia, South Korea, Spain, Turkey, Ukraine, United Kingdom PO / Tablet Janssen Research & Development 01 Nov 2015
Prostate cancer along with Androgen Deprivation Therapy (ADT) Adjunctive treatment, Metastatic disease Phase III China, Germany, Mexico PO / Tablet Janssen Research & Development 27 Nov 2015
Prostate cancer - Combination therapy, Late-stage disease Phase III China PO / Tablet Aragon Pharmaceuticals 19 Nov 2015
Prostate cancer - Combination therapy, Late-stage disease Phase III Argentina, Belgium, Czech Republic, France, Germany, Israel, Malaysia, Mexico, Netherlands, Poland, Romania, Russia, South Korea, Spain, Sweden, Taiwan, Turkey, USA, Ukraine, United Kingdom PO / Tablet Janssen Research & Development 30 Nov 2016
Prostate cancer along with Androgen Deprivation Therapy (ADT) Hormone refractory, Metastatic disease, Newly diagnosed Phase III Sweden PO / Tablet Janssen Research & Development 01 Nov 2015
Prostate cancer - Combination therapy, Hormone refractory, Metastatic disease Phase II USA PO / Capsule Janssen Research & Development 01 May 2016
Prostate cancer - Neoadjuvant therapy Phase II Singapore PO / Tablet Singapore General Hospital 20 Jun 2017
Prostate cancer - Combination therapy Phase II Brazil PO / unspecified Instituto do Cancer do Estado de Sao Paulo, Janssen Research & Development 24 Jan 2019
Prostate cancer - Combination therapy, Newly diagnosed Phase II USA PO / Tablet Janssen Research & Development 06 Feb 2017
Prostate cancer - Neoadjuvant therapy Phase II USA PO / Tablet Janssen Research & Development, M. D. Anderson Cancer Center 22 Mar 2018
Prostate cancer - Combination therapy, Neoadjuvant therapy Phase II USA PO / Tablet Case Comprehensive Cancer Center 01 Oct 2016
Prostate cancer - First-line therapy, Late-stage disease, Metastatic disease, Monotherapy Phase II Brazil PO / Tablet Janssen Research & Development 11 Oct 2017
Prostate cancer - Combination therapy, Hormone refractory Phase II USA PO / Tablet Dana-Farber Cancer Institute, Janssen Research & Development 23 Jun 2017
Prostate cancer - Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater No development reported (I) Belgium, Canada, Italy, Netherlands, Russia, Spain, USA PO / Tablet Janssen Research & Development 28 Jun 2022
Prostate cancer - Hormone refractory, Metastatic disease No development reported (I) China PO / unspecified Janssen Research & Development 28 Jun 2022
Salivary gland cancer - Combination therapy, Late-stage disease, Metastatic disease, Recurrent Phase II Japan PO / Tablet Janssen Research & Development 07 Apr 2020

Commercial Information

Involved Organisations

Organisation Involvement Countries
University of California Originator USA
Aragon Pharmaceuticals Originator USA
Janssen Research & Development Owner USA
Nippon Shinyaku Collaborator Japan
Duke University Medical Center Collaborator USA
National Cancer Institute (USA) Collaborator USA
Instituto do Cancer do Estado de Sao Paulo Collaborator Brazil
University of Washington Collaborator USA
Institut Paoli-Calmettes Collaborator France
Janssen-Cilag Collaborator Netherlands
Cambridge University Hospitals Collaborator United-Kingdom
Singapore General Hospital Collaborator Singapore
Case Comprehensive Cancer Center Collaborator USA
Dana-Farber Cancer Institute Collaborator USA
M. D. Anderson Cancer Center Collaborator Usa
European Organisation for Research and Treatment of Cancer Collaborator Belgium
Memorial Sloan-Kettering Cancer Center Collaborator USA
Latin American Cooperative Oncology Group Collaborator Brazil
Weill Cornell Medical College Collaborator USA

Brand Names

Brand Name Organisations Indications Countries
ERLEADA Janssen Research & Development Prostate cancer Brazil, Canada, Japan
ERLYAND Janssen Research & Development Prostate cancer Australia
Erleada Janssen Research & Development Prostate cancer USA

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
Cancer - Prostate ex US Johnson & Johnson Marketed 2019 100 2030 - 05 Nov 2023
Cancer - Prostate US Johnson & Johnson Marketed 2018 100 2030 15 Sep 2030 05 Nov 2023

Credit Suisse Financial Forecast

Indication Region 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 Last Update
Cancer - Prostate ex US 478 913 1324 1695 2033 2338 2619 2829 3055 3300 05 Nov 2023
Cancer - Prostate US 813 968 1113 1247 1371 1481 1570 1633 1698 1834 05 Nov 2023
Total 1291 1881 2437 2942 3404 3819 4189 4462 4753 5134

Scientific Summary

  • Adverse Events Occasional: Accidental falls; Appetite disorders; Arthralgia; Diarrhoea; Exanthema; Fracture; Hot flashes; Hypertension; Nausea; Oedema; Seizures; Weight loss

Pharmacokinetics

Results from 1206 patients in the phase II SPARTAN trial showed that Mean (coefficient of variation [CV]%) PK exposure levels measured as AUC24 for apalutamide and active metabolite N-desmethyl APA (NAPA), respectively, were 117 (24 CV%) μg h/mL and 155 (17 CV%) μg h/mL for apalutamide-treated pts without dose reductions/interruptions, and 112 (24 CV%) μg h/mL and 148 (18 CV%) μg h/mL for those with dose reductions/interruptions [35] [38] .

Initial results from the phase II NEAR trial in patients with prostate cancer demonstrated reduction of serum PSA of 93.4% after administration of neoadjuvant apalutamide alone (range 61.2 to 99.3, p=0.0005) [74] [76] .

Adverse Events

Treatment with oral apalutamide, in combination with androgen deprivation therapy (ADT), was tolerated in the phase III SPARTAN trial. Final results from the trial showed grade 3/4 TEAEs of special interest including rash (5.2%), fractures (4.9%), falls (2.7%), ischemic heart disease (2.6%), hypothyroidism (0%) and seizures (0%).There was maintenance of overall health-related quality of life in patients with non-metastatic prostate cancer in the phase III SPARTAN trial. Exanthema (5.2% versus 0.3%), accidental falls (1.7% versus 0.8%) and fracture (2.7% versus 0.8%) were the most common Grade 3/4 treatment-emergent adverse events (TEAEs) for apalutamide in combination with ADT versus placebo in combination with ADT. Treatment discontinuation due to adverse events were 11% in the treatment arm as compared to 7% in the placebo arm. Both the treatment and the placebo arms had similar rates of serious adverse events (SAEs) (25% versus 23%, respectively). The most common side effects (= 10%) of treatment with oral apalutamide included fatigue, hypertension (14.3% vs 11.8%), rash (5.2% vs 0.3%), diarrhoea, nausea, weight loss, arthralgia, falls (1.7% vs 0.8%), hot flush, decreased appetite, fractures (2.7% vs0.8%) and peripheral oedema. Severe side effects associated with oral apalutamide treatment were falls, fractures and seizures. The double-blind trial randomised 1207 patients in the ration 2:1 to receive apalutamide in combination with ADT, or placebo in combination with ADT. The trial evaluated patients every 16 weeks for signs of disease progression [39] [118] [31] [119] [34] . Updated results from 1206 patients showed that AEs led to dose reduction/interruption were reported in 33% of apalutamide treated patients versus 19% placebo treated patients with average daily dose of 225 mg apalutamide versus 229 mg placebo in pateints with dose reduction/interruption. Rates of discontinuation due to progressive disease and adverse events were 34% and 14%, for the apalutamide group, and 74% and 8% for the placebo group [35] [38]

In the phase III ACIS trial, treatment with apalutamide in combination with abiraterone acetate was found o be generally safe and well tolerated. There were no new safety signals observed. Grade 3/4 treatment emergent adverse events (TEAEs) were reported in 63.3% in the combination arm versus 56.2% in the control arm. Grade 3/4 TAEs that occurred more frequently in the combination versus control arm included fatigue (4.7% vs 3.9%), hypertension (20.6% versus 12.5%), fall (3.3% versus 0.6%), skin rash (4.5%vs. 0.4%), cardiac disorders (9%vs 5.7%), fractures and osteoporosis (4.1% vs 1.4%), and seizures (0.2%vs 0). Quality-of-life was comparable between treatment arms per Functional Assessment of Cancer Therapy–Prostate – (FACT-P Total) [43] [44]

Resultd from phase III TITAN trial showed the frequency of treatment-emergent adverse events (TEAEs) 96.4% with APA and 98.2% with PBO treatment. Skin rash incidence during apalutamide treatment (43.6%) was higher than on PBO (10.9%) [46] . Treatment with apalutamide to androgen deprivation therapy (ADT), compared with placebo plus ADT, was safe and generally well tolerated, in patients (n=1 052) with metastatic castration-sensitive prostate cancer, in the phase III TITAN trial. Final results from the trial showed consistent safety and tolerability profile of apalutamide with previously reported studies [47] . Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The most common grade 3/4 adverse events for apalutamide plus androgen deprivation therapy (ADT), versus placebo plus ADT, were similar (42% versus 41%). The most common grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4% versus 9.1%), hot flush, fatigue, arthralgia and skin rash (6.3% versus 0.6%). Additional reported grade 3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3% versus 2.7%), blood alkaline phosphatase increased (0.4% versus 2.5%) and anaemia (1.7% versus 3.2%). Treatment discontinuation due to AEs was 8% in the apalutamide arm, compared with 5% in the placebo arm. Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27% versus 9%, respectively) [50] [49] [52] . Results from an interim analysis of 525 patients indicated well tolerable safety profile for apalutamide in patients with -sensitive prostate cancer . Rates of grade 3/4 adverse events were 42% in apalutamide group while 41% in placebo group. Discontinuations due to adverse events were 8% in apalutamide group while 5% in placebo group [48] .

Prostate cancer

Phase III

Results from the phase III PRESTO trial in patients with high-risk biochemically relapse (BCR) prostate cancer showed that intensified androgen deprivation therapy (ADT) with addition of apalutamide or apalutamide plus abiraterone showed no new safety concerns. The most common grade ≥2 adverse event (AE) was hypertension (19%, 23%, 30% in androgen deprivation therapy (ADT), apalutamide in combination with ADT, and apalutamide in combination with ADT and abiraterone acetate plus prednisone arms, respectively). Three (2.1%) and five (3.4%) patients stopped treatment for adverse events in the apalutamide in combination with ADT and apalutamide in combination with ADT and abiraterone acetate plus prednisone arms, respectively. The open-label, parallel, randomised, three-arm trial enrolled 504 patients to ADT (n=167), apalutamide in combination with ADT (n=168) or apalutamide in combination with ADT and abiraterone acetate plus prednisone(n=169) arms [57] [56]

JNJ 56021927 was safe and well tolerated in patients with metastatic hormone-refractory prostate cancer in the phase I component of a phase I/II trial (ARN-509-001). The most common adverse events were fatigue of Grades 1 and 2 and GI toxicities [87] . This tolerability was confirmed in the phase II portion of this study, in which patients received 240mg JNJ 56021927 once daily [86] .

Treatment with apalutamide, in combination with abiraterone acetate, docetaxel and prednisone, was safe and generally well tolerated in patients with metastatic castration-resistant prostate cancer. No DLT was occurred with 120mg of apalutamide and 1 out of 6 patients, treated with 240mg apalutamide, had possibly related grade 3 hypertension [109] [110] .

Initial results from the phase II NEAR trial apalutamide exhibited a reasonable safety profile. One patient had an unrelated grade III adverse event, and none of the patients reported Clavien-Dindo grade III and above surgical complications [74] [76] .

Results of the phase II trial showed that neoadjuvant apalutamide (APA) plus leuprolide (LHRHa) with or without abiraterone (AA) was tolerable in localized high-risk prostate cancer (LHRPC) in patients with prostate cancer. Treatment was well tolerated with grade 3 hypertension in seven (two APA + LHRHa) [60] [59] .

Results of the randomised, open-label, phase II LACOG 0415 trial of abiraterone acetate plus prednisone (AAP) added to androgen deprivation therapy (ADT), versus apalutamide alone (APA) versus abiraterone plus apalutamide (AAP+APA) in patients with (n = 128) hormone naïve, locally advanced or metastatic prostate cancer, with non-castrate testosterone levels showed that APA alone had less toxicity. Treatment-related adverse events (TRAEs) rates of any grade were 71% in AAP+ADT arm, 64% in APA, and 65% in APA+AAP. TRAEs rates of Grade≥3 were 12% in AAP+ADT arm, 9% in APA and 16% in APA+AAP. Nine patients (7%) discontinued the treatment before the week 25, five (4%) of them due to toxicity, including one patient from AAP+ADT, two patients from APA, and six patients from APA+AAP [72] [71] .

Results from a phase II trial in patients (n=64) with prostate cancer demonstrated limited toxicities and manageable safety profiles. Fifteen patients experienced transient Grade 3 toxicities: 12 (18.8%) with hypertension and 3 with rash (4.7%). EPIC-26 scores for a subset of patients (n=21) at baseline and 12 months showed no significant decline in urinary or bowel domains; declines in sexual (-11.9) and hormone (-5.7) domains met significance [80] [79] .

Results from phase II study of apalutamide prior to radical prostatectom in patients (n=43) with prostate cancer demonstrated that apalutamide was well tolerated with one patient discontinuing early for a grade 3 rash [68] [67]

Results from phase III ACIS trial in patients with metastatic castration-resistant prostate cancer demonstrated similar treatment-emergent adverse events (TEAEs) in (all > 94%) in patients with VD, ≥ 75 y, and overall safety population. Hypertension was more frequent with APA + AAP vs AAP mainly in patients ≥ 75 y (31.7% vs 17.6%). Grade 3/4 TEAEs (APA + AAP vs AAP): VD, 60.8%, n = 74 vs 48.5%, n = 68; ≥ 75 y, 71.5%, n = 186 vs 68.5%, n = 165. Overall, 63.3%, n = 490 vs 56.2%, n = 489. TEAEs leading to discontinuation: VD, 17.6% vs 5.9%; ≥ 75 y, 26.3% vs 20.6%; overall, 16.9% vs 12.5%. TEAEs leading to death: VD, 6.8% vs 5.9%; ≥ 75 y, 5.4% vs 13.9%; overall, 3.5% vs 7.6%. [44] [45] .

In phase II trial, there were 2 grade (G) 5 adverse events (AEs) in the AAP arm (pulmonary embolism and sudden death, both after surgery). Nine (14.5%) patients (6 in A-APA; 3 in AAP) experienced G3-4 treatment-related AEs. The most common G3-4 AEs were hypertension (11.3%), AST/ALT elevations (3.2%) and skin rash (1.6%) [64]

Results from phase II trial demonstrated that the APA+GOS was well-tolerated and grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) patients, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1) [91] [92]

The updated results of part 2 phase II trial in prostate cancer demonstrated well tolerated profile. Of the 37 patients receiving AAPL on Arm 2A, 28 (75.7%) experienced any grade treatment-related adverse event (TRAE) and 4 (10.8%) had grade 3-4 TRAE. The most common any grade TRAE were fatigue (27%) and hypertension (16%) [85] . Results from part 1 and part 2 of phase II trial in prostate cancer showed that no new safety signals [83] [82] [84] .

Results from phase II trial demonstrated treatment-emergent adverse events (TEAEs) occurred in all 12 patients (100%). TEAEs were consistent with known safety profiles for each drug administered separately [61] [62]

Pharmacodynamics

Summary

Preclinical results demonstrated that LuCaP 77 progression was inhibited by castration and the additional treatments further inhibited tumour volume in the combination group, in patient-derived prostate cancer xenografts (PDXs) models. Castration in combination with docetaxel demonstrated the most significantly improved survival benefit (10w vs 16.5w median survival; HR = 0.2, p < 0.001), while castration combined with docetaxel resulted in a smaller survival benefit (10w vs 12.5w, median survival HR = 0.5, p = 0.036). LuCaP 147 exhibited similar responses to castration as LuCaP 77 but only small additional inhibition of tumour volume with the combination additional treatments and no significant survival improvements over castration alone. LuCaP 35 was the most responsive to castration and the additional treatments did not enhance the tumour volume inhibition, decreases in serum PSA or survival. Preliminary IHC analyses no significant decrease in AR or GR in the xenografts was observed, however, decrease in PSA indicated the efficacy of androgen suppression. Decreased proliferation (Ki67) was observed in LuCaP 77 and LuCaP 147 after castration and more pronounced decreases in the combination vs castration groups in LuCaP 77 and docetaxel and the combination vs castration in LuCaP 147 with no difference detected in LuCaP 35 [120] .

Results of the phase II trial of neoadjuvant apalutamide (APA) plus leuprolide (LHRHa) with or without abiraterone (AA) in localized high-risk prostate cancer (LHRPC) in patients with prostate cancer showed that pre-surgical PSA was ≤0.1 in 62/63 (98%). Despite uniformity in PSA response, the heterogeneity in measures of tumour viability showed TV (0-11.5cc), TC (1-80%), TEV (0-6.1cc). The ≤ypT2N0 associates with diagnostic biopsy positivity for the prespecified molecular signature (p <0.0001), PTEN expression (p: 0.004), absence of cribriform/ intraductal spread (p 0.002) but not with Gleason score. On multivariate analysis, only the prespecified biopsy signature associates with outcome (p 0.003). Findings were replicated when analyzed by TV, TC and TEV measures [60] [59] .

Therapeutic Trials

In the phase III SPARTAN trial, final results demonstrated prolonged median overall survival by 14 months and decreased the risk of death by 22% with apalutamide plus androgen-deprivation therapy (ADT). In a apalutamide plus ADT treatment group, median OS was significantly longer, with 73.9 months for patients, compared to 59.9 months with patients receiving placebo in combination with ADT [HR=0.78; p=0.0161 (to reach statistical significance, a p-value of p<0.046 needed to be observed)]. In a crossover group that received apalutamide plus ADT after placebo treatment, exceedeing median OS compared to placebo plus ADT with a difference of 21 months between the two arms (73.9 months vs 52.8 months, respectively, HR=0.69, p=0.0002) was observed. In apalutamide plus ADT treatment group median treatment duration was nearly three times longer for patients (33 months) compared with the those treated with placebo plus ADT (12 months) [39] . At the 52 month follow up, metastasis free survival and overall survival improved to a greater extent with the apalutamide containing regimen. In addition, apalutamide was associated with significant benefits on the FACT-P total score from baseline to cycles 21 and 25, versus placebo (p=0.0138 and 0.0009, respectively). Favourable scores on FACT-P and EQ-5D-3L were maintained with apalutamide, while placebo group scores declined over time (approximately one year). Additionally, treatment with ERLEADA® in combination with ADT significantly delayed patients' time to cytotoxic chemotherapy compared to placebo in combination with ADT (HR=0.63; p=0.0002). Initial results showed that apalutamide significantly decreased the risk of prostate specific antigen (PSA) progression by 94%, compared with the placebo group (HR=0.06; 95% CI, 0.05-0.08; P < 0.0001). The median time to PSA response was 29 days in the apalutamide plus androgen-deprivation therapy (ADT) group and 12 weeks after randomization, median PSA decreased by 90% in the apalutamide group and increased by 40% in the placebo group. The baseline median PSA doubling time was 4.4 and 4.5 months, and median baseline PSA was 7.78 and 7.96 ng/mL in the apalutamide and placebo groups, respectively. Treatment with oral apalutamide significantly delayed the development of metastasis in patients with non-metastatic prostate cancer that had become resistant to standard ADT. The average progression-free survival was 40.2 months for patients in the treatment group as compared with 16.2 months for patients in the placebo group. Thus, median metastasis-free survival (MFS) was prolonged by more than two years with oral apalutamide (difference of 24.3 months). The risk of metastasis or death was decreased by 72% as compared with placebo (HR = 0.28; 95% CI, 0.23-0.35; P < 0.0001). Administration of apalutamide also reduced other signs of disease progression, including development of imaging-confirmed metastasis or symptoms such as bone pain, and death from any cause. The double-blind trial randomised 1207 patients in the ration 2:1 to receive apalutamide in combination with ADT, or placebo in combination with ADT. Statistically significant improvements were shown for secondary endpoints, including time to metastasis, progression-free survival and time to symptomatic progression. The trial evaluated patients every 16 weeks for signs of disease progression. The patient-reported outcomes data indicated that adding apalutamide to ADT in patients with non-metastatic castration-resistant prostate cancer, did not have a significant impact on individuals' overall health-related quality of life (HRQoL). In this exploratory analysis, patients did not experience notable disruptive changes after the addition of apalutamide to the standard of care [31] [32] [9] [121] [34] [33] . Updated results from 1206 patients showed that metastasis-free survival benefit was similar across the range of apalutamide(APA0 and its active metabolite N-desmethyl APA (NAPA) exposures. In univariate and multivariate Cox regression models, no significant differences in the exposure-MFS relationship were observed for APA and NAPA [35] .The results from the second interim analysis showed that treatment with apalutamide in patients with high-risk of developing metastases, resulted in a 25% reduction in the risk of death compared with placebo plus ADT (HR = 0.75; 95% CI, 0.59–0.96; p = 0.0197). For patients treated with apalutamide, a longer median follow-up of 41 months was observed and four-year OS rates were 72.1%, whereas for patients treated with placebo the OS rates were 64%. During the interim analysis the subsequent life-prolonging therapy was 68% in the placebo group and 38% in the apalutamide group. The OS benefit of apalutamide was consistent across baseline subgroups, such as race, prior treatments, baseline PSA and performance status. This interim analysis was conducted when 68% of the required OS events had been observed, compared with the original report when only 24% of required OS events had occurred (HR = 0.70; 95% CI, 0.47–1.04; p = 0.07) [117] [36] [38] .

In the phase III ACIS trial, treatment with apalutamide in combination with abiraterone acetate met the primary endpoint of radiographic progression-free survival (rPFS) with a 31% reduction in the risk of radiographic progression or death in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy. The median rPFS was found to be extended by six months in patients treated in the combination arm as compared with patients in the control arm (22.6 vs 16.6 months; hazard ratio [HR] 0.69 [95% CI, 0.58-0.83]; p<0.0001). The HR for radiographic progression or death as assessed by blinded independent central review (BICR) was 0.864 [95% CI, 0.718–1.040]. At a median follow-up time of 54.8 months, a reduction of 30% was seen in the risk of radiographic progression or death in the combination arm as compared with the control arm (median time to rPFS 24 vs 16.6 months: HR 0.70 [95% CI, 0.60-0.83]). No statistically significant difference was observed for secondary endpoints including overall survival (OS), time to initiation of cytotoxic chemotherapy, chronic opioid use, and pain progression between treatment arms [43] [44] .

Updated efficacy data from the statistical extrapolations of the phase III TITAN study demonstrated that the best fit extrapolation estimated median OS of 71.8 months for the overall mHSPC population treated with APA (Table), leading to an estimated median improvement of up to 32 months versus PBO. Median OS values predicted by the other five models ranged from 62.4 to 78.1 months [55] . Updated efficacy results from phase III trial in prostate cancer showed that 49% of patients with evaluable UL PSA values achieved UL2 PSA during the study. By 3 months, UL1 and UL2 were achieved in 38% and 23% of APA patients and 15% and 5% of PBO patients, respectively. By 6 months, these values were 29% and 36% (APA), and 17% and 6% (PBO). Patients with UL1/UL2 at 3 months had lower baseline PSA and higher percentage of low-volume disease vs PSA>0.2 ng/mL. Patients with UL1/UL2 at 3 or 6 months had improved long-term outcomes irrespective of volume. At 42 months' follow-up post-landmark, survival rates were 89 (81-94), 81 (75-85), and 34 (26-43) when UL2 was achieved at 3 months, after 3 months, or never after 3 months, and 89 (83-93), 77 (70-83), and 34 (26-43) when UL2 was achieved at 6 months, after 6 months, or never after 6 months [54] . Results from the phase III TITAN trial found that apalutamide (APA) + androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival and overall survival (OS) compared to placebo (PBO) + ADT in patients with metastatic castration-sensitive prostate cancer (mCSPC). The prevalence of these biomarkers significantly increased from baseline (BL) to end of study treatment (EOST). Among pts in both treatment groups, 36% had detectable circulating tumor (ctDNA), of which 27% had any genomic androgen receptor (AR) aberration and 24% had AR gene amplification at BL. The most common non-AR aberrations at BL (TP53, HRR pathway, PTEN, RB1, and PIK3CA genes) increased at EOST but not significantly. In multivariate analyses involving data from both treatment groups, the presence of ctDNA or any AR genomic aberrations at BL (HR, 1.9 or 6.7; all p < 0.05) and any AR genomic aberrations or PI3K pathway activation at EOST (1.7, p < 0.05 or 2.2, p < 0.001) were significantly associated with poor OS. Only PIK3CA activation, PI3K pathway activation, or TP53 inactivation at EOST were associated with worse OS in univariate analyses of patients who received subsequent therapy (chemotherapy: 106; hormonal therapy: 161) (3.7, p < 0.05; 2.4, p < 0.05; 3.0, p < 0.01, respectively). This was true for patients who received chemotherapy. Interpretation is constrained by the small sample size in some biomarker subgroups [53] . Results from the phase III TITAN trial demonstrated that the final analysis of rPFS, APA group had a statistically significant longer rPFS compared to PBO group (Hazard ratio (HR) 0.511, 95% CI 0.305, 0.856; p=0.0094). In the final analysis of OS with a median follow-up duration of 42.5 months, there was a trend for improved OS in the APA group compared to PBO (HR 0.685, 95% CI 0.416,1.126; p=0.1335) that was consistent with the overall population. TTCR and TTPP were significantly improved in APA versus PBO group (HR 0.309, 95% CI 0.206, 0.463; p<0.001); HR 0.213, 95% CI 0.131, 0.346; p<0.001, respectively) [46] . In the phase III TITAN trial, the four-years of median follow-up, final analysis data demonstrated a statistically significant overall survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). Apalutamide plus ADT showed a statistically significant improvement in OS with a 35% reduction in risk of death versus ADT alone (HR 0.65; p<0.0001). The results were similar to the primary analysis of the trial despite the subsequent crossover rate of almost 40% of the placebo-controlled group to the apalutamide arm. The improvement in OS increased to a 48% reduction in risk of death after adjusting for patients who crossed over (HR 0.52; p<0.0001). There was consistent benefit across other endpoints, including improved second progression-free survival (PFS2) (HR 0.62; p<0.0001) and delayed castration resistance (HR 0.34; p<0.0001). In addition, health-related quality of life (HRQoL), per total Functional Assessment of Cancer Therapy–Prostate (FACT-P), continued to be maintained with apalutamide [47] . Results from the phase III TITAN trial showed that the addition of apalutamide to androgen deprivation therapy (ADT), compared with placebo plus ADT, significantly improved the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS), and secondary endpoint of prolonged time to cytotoxic chemotherapy in patients (n=1 052) with metastatic castration-sensitive prostate cancer (mCSPC). Apalutamide plus ADT significantly extended OS, compared with placebo arm, with a 33% reduction in the risk of death (HR = 0.67; 95% CI, 0.51-0.89; P = 0.0053) and showed 61% risk reduction, compared with placebo plus ADT (HR = 0.39; 95% CI, 0.27-0.56; P < 0.0001). In exploratory endpoints, median time to PSA progression was more favourable following apalutamide plus ADT, compared with placebo plus ADT, and PSA reached undetectable levels in 68% of patients in the apalutamide plus ADT arm and 29% in patients in the placebo plus ADT arm. Also apalutamide plus ADT significantly improved rPFS, compared with the placebo arm, with a 52% reduction in risk of radiographic progression or death, compared with placebo plus ADT (HR = 0.48; 95% CI, 0.39-0.60; P < 0.0001). Additionally, apalutamide plus ADT, achieved a 34% risk reduction in median time to second progression-free survival (PFS2), compared with placebo plus ADT (HR = 0.66; 95% CI, 0.50-0.87). The median PFS2 was not reached for both study arms. Also, time to pain progression was did not reach statistical significance. The two-year OS rates, after a median follow-up of 22.7 months, were 82% for apalutamide plus ADT, compared with 74% for placebo plus ADT. Additionally, apalutamide plus ADT, compared with placebo plus ADT, achieved a 34% risk reduction in median time to second progression-free survival (PFS2) (HR = 0.66; 95% CI, 0.50-0.87). Although time to pain progression did not reach statistical significance [50] [49] [52] . Results from an interim analysis of 525 patients indicated apalutamide improved radiographic progression-free survival (rPFS) (HR, 0.48; 95% CI, 0.39 - 0.60; p < 0.0001), with a 52% reduction in risk of death or radiographic progression. Median rPFS was not reached in the apalutamide group and was 22.1 months in the placebo group. Treatment also improved overall survival (HR, 0.67; 95% CI, 0.51 - 0.89; p = 0.0053), with a 33% reduction in risk of death. Median overall survival was not reached in the apalutamide or placebo group. Time to initiation of cytotoxic chemotherapy was significantly improved with apalutamide (HR, 0.39; 95% CI, 0.27-0.56; p < 0.0001) [48] .

Prostate cancer

Phase III

Results from the phase III PRESTO trial in patients with high-risk biochemically relapse (BCR) prostate cancer showed that intensified androgen deprivation therapy (ADT) with addition of apalutamide or apalutamide plus abiraterone each prolonged biochemical progression-free survival (PFS). Median time from randomization to last contact was 26.5 and 26.8 months, for the two treatment comparisons. Both experimental arms prolonged prostate-specific antigen progression-free survival (PSA-PFS) compared to control (apalutamide in combination with ADT vs ADT HR=0.59, 97.5% CI: 0.40–0.85, 1-sided p-value=0.0006; apalutamide in combination with ADT and abiraterone acetate plus prednisone vs ADT, HR=0.53, 97.5% CI: 0.36–0.77, p-value=1-sided 0.00006). Median time to testosterone recovery was 3.9, 3.8 and 4.7 months in androgen deprivation therapy (ADT), apalutamide in combination with ADT, and apalutamide in combination with ADT and abiraterone acetate plus prednisone arms, respectively. The open-label, parallel, randomised, three-arm trial enrolled 504 patients to ADT (n=167), apalutamide in combination with ADT (n=168) or apalutamide in combination with ADT and abiraterone acetate plus prednisone(n=169) arms [57] [56]

JNJ 56021927 was associated with durable declines in prostate-specific antigen levels at all dose-levels in the phase I component of a phase I/II trial in men with progressive metastatic hormone-refractory prostate cancer (ARN-509-001) [87] . PSA decreases of ≥ 50% from baseline were seen in 88% and 29% of treatment-naive (TN) and abiraterone acetate-treated patients (PA), respectively, in the phase II portion of this trial. Median time to PSA progression was 16 weeks in the PA cohort, and has not been reached in the TN cohort. Among treatment-naive patients with measurable disease at baseline, objective response rate following JNJ 56021927 treatment was 63%. For patients with non-metastatic prostate cancer, a ≥ 50% decline in PSA was seen in 91% of participants through 24 weeks of the study. A total of 55% of patients had a ≥ 90% PSA decrease at 24 weeks, and median time to PSA progression had not been reached at this point. The phase II portion of this study enrolled patients across three disease cohorts: non-metastatic castration-resistant prostate cancer, metastatic disease that progressed following abiraterone acetate treatment, and treatment-naive metastatic disease [86] .

Phase II

In the phase II NEAR trial, treatment with apalutamide resulted in post-prostatectomy nadir PSA levels being achieved by 84% patients while the rest achieved nadir PSA levels of 0.03-0.05. The median reduction of serum PSA after neoadjuvant apalutamide alone was 97.3% (range 61.2 to 100.0, p<0.0001). Earlier reported results demonstrated median reduction in residual cancer burden (RCB) of 19% (range 7% to 40%, p=0.0037. The median RCB index was 1.80 (1.28 to 3.48) [75] [74] [76] .

Results of the phase II trial of neoadjuvant apalutamide (APA) plus leuprolide (LHRHa) with or without abiraterone (AA) in localized high-risk prostate cancer (LHRPC) in patients with prostate cancer demonstrated tumour regression in a subset of localized high-risk prostate cancer (LHRPC) patients. Dual androgen signaling inhibitors (ASI) treatment does not further improve outcomes. Organ confined disease (≤ypT2N0) found in 41% (13/32) APA+LHRHa vs 39% (12/31) APA+AA+LHRHa treated. Two (3%) had pathologic complete remission (APA+AA+LHRHa), six (10%) minimal residual disease (five on APA + LHRHa) [60] [59] .

Updated results of the randomised, open-label, phase II LACOG 0415 trial showed that patients with (n = 128) advanced castration sensitive prostate cancer treated with androgen deprivation therapy (ADT) with abiraterone acetate plus prednisone (ADT+AAP), apalutamide alone (APA), or apalutamide with AAP (APA+AAP) had high rates of prostate-specific antigen (PSA) response and favorable two year overall survival (OS). PSA ≤ 0.2 ng/mL at week 25 seemed to be a surrogate prognostic predictor of OS in advanced castration sensitive prostate cancer. In the overall sample, patients with PSA ≤ 0.2 ng/mL at week 25 had higher two year OS rate than those with PSA > 0.2 ng/mL at week 25 (92.9% versus 85.0%), however without statistical significance. About 128 patients were randomized to the ADT+AAP (n = 42), APA (n = 42), and APA+AAP (n = 44) arms. At week 25, PSA≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%-87.6%), 60.0% (95%CI 43.3%-75.1%), and 79.5% (95%CI 63.5%-90.7%) of patients in the ADT+AAP, APA, and APA+AAP arms, respectively. 110 patients continued treatment after week 25. At the two year visit, 80 (62.5%) patients remained on the study medication. Median time-to-treatment failure (TTF) was 24.0 months (95%CI: 23.3, 24.0) with ADT+AAP, 24.0 months (95% CI: not estimated) with APA, and 24.0 months (95% CI: 13.0, 24.0) with APA+AAP. The main reasons for treatment discontinuation were disease progression (n = 8, 6.3%), toxicity (n = 10, 7.8%), death (n = 6, 4.7%), withdrawal (n = 4, 3.1%), and other (n = 19, 14.8%). The estimated proportion of patients who were alive at two years OS (2y-OS rate) was 92.5% (95% CI: 84.3, 100) with ADT+AAP, 87.9% (95% CI: 77.9, 97.8) with APA, and 92.7% (95% CI: 84.8, 100) with APA+AAP (p = 0.5926). The two years OS was 92.9% (95% CI: 85.3, 96.2) in patients with PSA ≤ 0.2 ng/mL at week 25, while two years OS was 85.0% (95% CI: 72.9, 97.1) in patients with PSA > 0.2 ng/mL at week 25 (p = 0.1250) [73] . Interim results showed high effectiveness in terms of PSA response in evaluable patients with (n = 122) hormone naïve, locally advanced or metastatic prostate cancer, with non-castrate testosterone levels. Radiologic disease control and the decline of ≥ 80% in PSA at week 25 were similar among all treatment arms. At week 25 the PSA was ≤ 0.2 ng/mL in 76% of patients in AAP+ADT arm, 59% in APA, and 80% in APA+AAP. All patients had a decline of ≥ 50% in PSA at week 25. About 97% had a decline of ≥ 80% in PSA at week 25, 100% of patients in AAP+ADT arm, 95% in APA and 98% in APA+AAP. A total of three patients had clinical progressive disease, one in each arm. Two out of those three patients also had radiological progression at week 25, one patient in AAP+ADT arm and one patient in APA [72] [71] .

Results from a phase II trial in patients (n=64) with prostate cancer demonstrated impressive 3 year biochemical recurrence-free survival (bRFS) and rapid T recovery. In the trial, 63 patients completed protocol treatment. Median time to nadir PSA from treatment start was 2 months (range, 1-9); 63 of 64 patients (98.4%) achieved an undetectable nadir PSA. Median time to post-treatment, non-castrate T was 6.5 months (range, 2.5-25.5). Median follow-up (f/u) for patients without BCR was 30 months (range, 15-44). Seven patients had BCR; 2-yr bRFS was 95.0% (95% CI, 89.7-100); 3-yr bRFS was 89.7% (95 CI, 81.0-99.3). For the 57 patients without BCR, 56 (98.2%) had T > 150ng/mL at last f/u; median PSA at last f/u was 0.10 ng/mL (IQR, <0.10-0.30); of these, 40 (70.2%) patients had PSAs ≤ 0.20 ng/mL with 24 (42.1%) undetectable [80] [79] .

Results from phase II study of apalutamide prior to radical prostatectomy in patients (n=43) with prostate cancer demonstrated >50% decline in PSA and expected elevations in testosterone while on drug, with normalization after discontinuation to a mean of 408 ng/dL. 18 (42%) of 43 patients completing surgery had high risk surgical pathology. Other pathologic observations included 9.3% PSM (0 in pT2, 4 in pT3a/b). All PSM were focal. Only 1 patient (2%) of 43 had a positive node with an extended template. There was one postoperative death unrelated (cardiac), 1 BCR with no treatment (pT2 disease), and 2 BCR leading to salvage RT (pT3a/b disease) [68] [67]

In phase II trial, there was no statistically significant difference between study arms regarding pCR/MRD or RCB ≤ 0.25 cm3 rates. Patients with complete PSMA-PET response (psmaCR) demonstrated a RCB ≤ 0.25 cm3 rate of 50% compared to 7.5% in pts without a psmaCR (P = 0.001). The rate of biochemical relapse (BR) was 14% for patients with RCB ≤ 0.25 cm3 versus 38% in patients with RCB > 0.25 cm3 (P = 0.118). At current median follow-up of 2.6 years, all patients with both psmaCR and RCB ≤ 0.25cm3 (N = 11, 18%) were free of BR [64] .

Results from phase II trial demonstrated that the this study did not meet the predefined criteria of efficacy. For the 24 primary RE patients, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the primary RE patients were 50.0% and 70.8%, respectively. Median PFS and OS in the treated patients were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos [91] [92]

The updated results of part 2 phase II trial in prostate cancer demonstrated favorable pathologic responses and 3-year biochemical progression-free survival (bPFS) in a subset of patients. Of patients not randomized to Part 2, 32.3% (n=10) had a pathologic complete response or minimum residual disease (tumor ≤5 mm) at radical prostatectomy (RP). 3-year bPFS was 81% for arm 2A and 72% for arm 2B; the difference was not statistically significant (HR 0.81 90% CI 0.43-1.49). Of patients randomized to Part 2, 81% of patients had testosterone recovery in the AAPL treated group compared to 95% in the observation group with median to recovery of 8.7 months compared to 4.0 months [85] . Previous results from part 2 of phase II trial in prostate cancer showed that in the intent-to-treat analysis, the 3-year biochemical progression-free survival (bPFS) estimate was 80% (95% CI:65-90%) for Arm 2A and 72% (95% CI:56-84%) for Arm 2B, which was not statistically significant (2-sided p=0.39). Patients who achieved pathologic responses (n=14) had longer bPFS than non-responders (log-rank test two-sided p=0.03; 3-year bPFS 100% vs 72%). In per-protocol population, of 36 patients receiving Arm 2A treatment with available data, 83% had testosterone recovery and median time to recovery from therapy end was 8.7 months. For patients on observation (n=42), 95% had testosterone recovery, and median time to recovery from RP was 4.0 months [84] . Results from part 1 of phase II trial in prostate cancer showed that the combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms [83] [82] .

Results from phase II trial demonstrated that the of the 12 patients who continued onto the main study, 1 withdrew and another was noncompliant with therapy and subsequently withdrew but maintained castration while on therapy. Of the 10 patients who successfully completed therapy, 100% maintained castration during 1 year of concomitant therapy with relugolix + Apa. No patient required dose modification of relugolix. Median T level was 10.0 ng/dL after 1 year of treatment. One month after treatment discontinuation, 8/10 (80%) patients saw recovery of their T (T ≥50 ng/dL).
[61] [62]

Future Events

Expected Date Event Type Description Updated
31 Aug 2023 Trial Update Janssen Research & Development plans a phase III LIBERTAS trial for Prostate cancer (Combination therapy, Metastatic disease) in USA and Germany (PO, Tablet) (700364618), (NCT05884398) 26 Sep 2023
07 Apr 2020 Trial Update Janssen plans a phase II trial for Salivary gland cancer (Combination therapy, Late-stage disease, Metastatic disease, Recurrent) in Japan, in April 2020 (NCT04325828) (700320318) 27 Apr 2020
31 Dec 2019 Regulatory Status Janssen announces intention to submit regulatory applications for approval of apalutamide for Prostate cancer in 2019 [51] 04 Jul 2022
15 Feb 2019 Trial Update Janssen Research & Development plans a phase III trial for Prostate Cancer (Late-stage disease) in USA, Argentina, Australia, Brazil, Canada, China, Czech Republic, France, Germany, Israel, Italy, South Korea, Netherlands, Poland, Spain, Taiwan and United Kingdom (700302539), (NCT03767244) 11 Jul 2019
26 Jun 2018 Trial Update Janssen Research & Development plans a phase I trial for Prostate Cancer in China (700295835), (NCT03523442) 04 Oct 2018
30 Apr 2018 Trial Update M.D. Anderson Cancer Center and Janssen plan a phase II trial for Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater), in April 2018 (NCT03360721) (700291008) 23 Mar 2018
13 Apr 2018 Trial Update NRG Oncology and National Cancer Institute plan a phase II trial in Prostate cancer (Late-stage disease) in USA in February 2018 (NCT03371719) (700291507) 22 Jun 2018
01 Apr 2018 Regulatory Status FDA assigns PDUFA action date of 01/04/2018 for apalutamide for non-metastatic castration-resistant Prostate cancer [12] 15 Feb 2018
01 Apr 2018 Trial Update M.D. Anderson Cancer Center and Janssen plan a phase II trial for Prostate cancer (Neoadjuvant therapy) in the US (NCT03412396) (700292600) 05 Apr 2018
01 Apr 2018 Trial Update Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute plan a phase II trial for Prostate cancer (Combination therapy, Metastatic disease) in USA, in March 2018 (NCT03436654) (700293288) 04 Oct 2018
31 Mar 2018 Trial Update Cambridge University Hospitals NHS Foundation Trust and Janssen-Cilag plans a phase II TAPS01 trial for Prostate cancer (First-line therapy, Newly diagnosed, Metastatic disease) in United Kingdom (EudraCT2017-001700-29) (NCT03365297) (700291139) 22 Jun 2018
19 Sep 2017 Trial Update M.D. Anderson Cancer Center plans a phase II trial for Prostate cancer (Combination therapy) in USA (NCT03279250) 08 Dec 2017
01 Jul 2017 Trial Update University of Athens plans a phase II trial for Prostate cancer (Metastatic disease, Late-stage disease) (NCT03173859) 07 Feb 2019
30 Jun 2017 Trial Update Dana-Farber Cancer Institute and Janssen plan a phase II trial for Prostate cancer (Combination therapy) in USA (NCT03141671) 30 Jan 2018
30 May 2017 Trial Update Duke University Medical Center and Janssen plan the PANTHER phase II trial for Prostate cancer (Metastatic disease, Combination therapy, Treatment-naive, Hormone refractory) (NCT03098836) 08 Dec 2017
01 May 2017 Trial Update Singapore General Hospital plans a phase II trial for Prostate cancer(Neoadjuvant therapy) (NCT03124433) 21 Nov 2017

Development History

Event Date Update Type Comment
25 Jan 2024 Scientific Update Updated efficacy and adverse events data from a phase II trial in prostate cancer presented at the 2024 Genitourinary Cancers Symposium (ASCO-GCS-2024) [85] Updated 18 Mar 2024
25 Jan 2024 Scientific Update Updated efficacy data from the phase III TITAN trial in Prostate cancer presented at the 2024 Genitourinary Cancers Symposium (ASCO-GeCS-2024) [55] Updated 13 Mar 2024
13 Dec 2023 Trial Update Aragon Pharmaceuticals completes a phase III expanded access protocol trial in Prostate cancer (Adjunctive treatment, Hormone refractory) in Brazil, Mexico and Colombia (PO) (NCT03523338) Updated 27 Dec 2023
05 Nov 2023 Financial Update Credit Suisse financial data update Updated 05 Nov 2023
25 Oct 2023 Trial Update Janssen Research & Development completes the phase II trial for Prostate cancer (Adjunctive treatment) in USA (PO) (NCT04523207) Updated 22 Dec 2023
20 Oct 2023 Scientific Update Efficacy data from the phase III trial in Prostate cancer were presented at the 48th European Society for Medical Oncology Congress (ESMO-2023) [54] Updated 18 Dec 2023
31 Aug 2023 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, Metastatic disease) in Poland, Germany, France, China, Canada, Brazil, Australia, USA (PO) (NCT05884398) Updated 18 Mar 2024
09 Aug 2023 Regulatory Status Health Canada approves Apalutamide 240mg once daily dose tablet for the treatment of metastatic castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer in Canada [5] Updated 14 Aug 2023
02 Jun 2023 Scientific Update Efficacy and adverse events data from phase II trial in for Prostate cancer presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [62] Updated 08 Jul 2023
02 Jun 2023 Scientific Update Efficacy and adverse events data from a phase I trial in Prostate cancer presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [84] Updated 04 Jul 2023
01 Jun 2023 Trial Update Janssen Research & Development plans a phase III LIBERTAS trial for Prostate cancer (Combination therapy, Metastatic disease) in USA and Germany (PO, Tablet) , (NCT05884398) Updated 26 Sep 2023
30 May 2023 Trial Update Janssen completes a phase II trial for Salivary gland cancer (Combination therapy, Late-stage disease, Metastatic disease, Recurrent) in Japan (NCT04325828) Updated 12 Jul 2023
28 Apr 2023 Scientific Update Efficacy and adverse events data from a phase III PRESTO trial in Prostate cancer presented at the 118th Annual Meeting of the American Urological Association (AUA-2023) [57] Updated 16 Jun 2023
03 Apr 2023 Phase Change - Marketed Launched for Prostate cancer (Hormone refractory) in USA (PO) [8] Updated 05 Apr 2023
03 Apr 2023 Phase Change - Marketed Launched for Prostate cancer (Metastatic disease, Adjunctive treatment) in USA (PO) [8] Updated 05 Apr 2023
13 Oct 2022 Trial Update Janssen completes a phase Ib trial in Prostate cancer (Hormone refractory) in USA, Canada, Moldova, Netherlands and United Kingdom (NCT02578797) Updated 30 Nov 2022
28 Jun 2022 Phase Change - No development reported No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in Spain, Russia, Netherlands, Italy, Canada, Belgium, USA (PO, Tablet) Updated 04 Jul 2022
28 Jun 2022 Phase Change - No development reported No recent reports of development identified for phase-I development in Prostate-cancer(Hormone refractory, Metastatic disease) in China (PO) Updated 28 Jun 2022
07 Jun 2022 Scientific Update Efficacy data from the phase III trial in Prostate cancer presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [53] Updated 12 Jul 2022
03 Jun 2022 Scientific Update Efficacy and adverse events data from phase-II trial in Salivary gland cancer presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [91] Updated 11 Jul 2022
03 Jun 2022 Scientific Update Efficacy and safety data from phase II trial in Prostate cancer presented at 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [64] Updated 04 Jul 2022
03 Jun 2022 Scientific Update Interim efficacy data from a phase II LACOG 0415 trial in prostate cancer presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [73] Updated 04 Jul 2022
03 Jun 2022 Trial Update Aragon Pharmaceuticals completes enrolment in its phase III ATLAS trial in Prostate cancer (Combination therapy, Late-stage disease) in Argentina, Belgium, Brazil, Canada, China, Czech Republic, France, Israel, Germany, South Korea, Malaysia, Mexico, Netherlands, Poland, Romania, Russia, Sweden, Taiwan, Turkey, Ukraine and United Kingdom, USA, Israel and Taiwan before June 2022 [40] Updated 04 Jul 2022
16 Mar 2022 Trial Update University of California in collaboration with Janssen Scientific Affairs initiates a phase II trial for Prostate cancer (Combination therapy; Hormone refractory, Metastatic disease; Second-line therapy; Late-stage disease) in US (NCT04926181) Updated 04 Apr 2022
12 Jan 2022 Trial Update University of Washington, in collaboration with the National Cancer Institute and Janssen terminates a phase II trial in Prostate cancer in USA (PO), due to slow accrual (NCT02721979) Updated 28 Jan 2022
05 Jan 2022 Biomarker Update Biomarkers information updated Updated 07 Jan 2022
11 Nov 2021 Trial Update Janssen Research & Development completes a phase I trial in Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in USA, Belgium, Canada, Italy, Netherlands, Russia and Spain (PO) (NCT03551782) Updated 11 Mar 2022
16 Sep 2021 Scientific Update Safety and efficacy data from phase III TITIAN trial in Prostate cancer presented at 46th European Society for Medical Oncology Congress [46] Updated 23 Nov 2021
13 Sep 2021 Scientific Update Efficacy data and adverse events data from a phase II trial in Prostate cancer presented at the 116th Annual Meeting of the American Urological Association (AUA-2021) [68] Updated 01 Nov 2021
07 Jul 2021 Trial Update Janssen completes a phase II trial in Prostate cancer (Late-stage disease, Metastatic disease, Combination therapy, First-line therapy) in Brazil (PO) (NCT02867020) Updated 15 Jul 2021
28 Jun 2021 Trial Update The Memorial Sloan-Kettering Cancer Center completes a phase Ib trial for Prostate cancer in USA (PO) (NCT02106507) Updated 13 Jul 2021
04 Jun 2021 Scientific Update Adverse events data from the phase III ACIS trial in Prostate cancer presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021) [45] Updated 24 Jul 2021
04 Jun 2021 Scientific Update Efficacy and adverse events data from a phase II trial in Prostate cancer presented at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO-2021) [80] Updated 24 Jul 2021
13 May 2021 Trial Update Janssen Cilag initiates phase III PRIMORDIUM trial for Prostate cancer (Hormone refractory) in Australia, Austria, Czech Republic, Denmark, Italy, Lebanon, Poland, Portugal, Russia, Sweden, Turkey (PO, Tablet) (EudraCT2019-002957-46) (NCT04557059) Updated 23 Nov 2021
11 May 2021 Trial Update Janssen in collaboration with M.D. Anderson Cancer Center completes a phase II trial for Prostate cancer (Second-line therapy or greater, Combination therapy) in USA (PO) (NCT03279250) Updated 27 May 2021
08 Mar 2021 Scientific Update Efficacy and adverse events data from a phase I trial in Prostate cancer released by Janssen Research and Development [83] Updated 04 Jul 2023
17 Feb 2021 Trial Update Janssen and M. D. Anderson Cancer Center suspend a phase II trial for Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in USA, due to decision of principle investigator (PO) (NCT03360721) Updated 22 Feb 2021
11 Feb 2021 Scientific Update Efficacy and safety data from the phase III ACIS trial for Prostate Cancer released by Janssen Pharmaceutical [43] Updated 11 Feb 2021
08 Feb 2021 Scientific Update Final efficacy and adverse event data from the phase III TITAN trial in Prostate cancer released by Janssen [47] Updated 10 Feb 2021
10 Dec 2020 Trial Update The National Cancer Institute and University of Washington completes a phase II trial for Prostate cancer (Combination therapy, Neoadjuvant therapy) in USA (PO) (NCT02849990) Updated 03 Feb 2021
24 Sep 2020 Trial Update Janssen Pharmaceutica and UNICANCER re-initiate the phase III CARLHA-2 trial in Prostate cancer (Combination therapy) in France (PO) (NCT04181203) (EudraCT2017-000155-21) Updated 01 Oct 2020
21 Sep 2020 Trial Update Janssen Pharmaceutical completes enrolment in the phase III ACIS trial in Postate cancer (Combination therapy, First-line therapy, Hormone-refractory, Metastatic disease) in USA, Argentina, Australia, Belgium, Brazil, Canada, France, Japan, South Korea, Mexico, the Netherlands, Russia, South Africa, Spain, Germany, Italy and United Kingdom (NCT02257736) (EudraCT2014-001718-25) [42] Updated 15 Feb 2021
19 Sep 2020 Scientific Update Updated efficacy data from the phase III SPARTAN trial in Prostate cancer presented at the 45th European Society for Medical Oncology Congress (ESMO-2020) [117] Updated 08 Oct 2020
19 Aug 2020 Trial Update Janssen Research & Development initiates a phase II trial for Prostate cancer (Adjunctive treatment) in USA (PO) (NCT04523207) Updated 18 Sep 2020
17 Aug 2020 Trial Update European Organisation for Research and Treatment of Cancer withdraws a phase III trial for Prostate cancer in Spain and Belgium (EudraCT2018-000899-15) Updated 27 Aug 2020
05 Jun 2020 Active Status Review 9294269 - No updates Updated 05 Jun 2020
29 May 2020 Scientific Update Interim efficacy and adverse events data from a phase II LACOG 0415 trial in prostate cancer presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [72] Updated 29 Jun 2020
29 May 2020 Scientific Update Interim efficacy, pharmacodynamics and adverse events data from a phase II neoadjuvant trial in prostate cancer presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [60] Updated 29 Jun 2020
29 May 2020 Trial Update Janssen Cilag initiates a phase III trial for Prostate cancer (Hormone refractory) in Spain (PO, Tablet) (EudraCT2019-002957-46) Updated 05 Jun 2020
29 May 2020 Phase Change - Registered Registered for Prostate cancer (Metastatic disease) in Japan (PO) [23] Updated 03 Jun 2020
15 May 2020 Scientific Update Updated efficacy data from the phase II NEAR trial in Prostate cancer presented at the 115th Annual Meeting of the American Urological Association (AUA-2020) [75] Updated 09 Jul 2020
15 May 2020 Scientific Update Final adverse events and efficacy data from a phase III SPARTAN trial in Prostate caner released by Janssen [39] Updated 15 May 2020
07 Apr 2020 Phase Change - II Phase-II clinical trials in Salivary gland cancer (Combination therapy, Metastatic disease, Late-stage disease, Recurrent) in Japan (PO) (NCT04325828) Updated 27 Apr 2020
31 Mar 2020 Trial Update Janssen Pharmaceutica and UNICANCER temporarily suspend the phase III CARLHA-2 trial in Prostate cancer (Combination therapy) in France (PO) due to COVID-19 pandemic (NCT04181203) (EudraCT2017-000155-21) Updated 05 May 2020
30 Mar 2020 Trial Update Janssen plans a phase II trial for Salivary gland cancer (Combination therapy, Late-stage disease, Metastatic disease, Recurrent) in Japan, in April 2020 (NCT04325828) Updated 27 Apr 2020
30 Jan 2020 Phase Change - Registered Registered for Prostate cancer (Metastatic disease, Hormone-sensitive) in European Union, Norway, Iceland, Liechtenstein (PO) [18] Updated 03 Feb 2020
30 Jan 2020 Regulatory Status European Commission approves for expanded use of apalutamide for the treatment of Prostate cancer (Metastatic disease, Hormone-sensitive) in the EU [18] Updated 03 Feb 2020
09 Jan 2020 Trial Update Janssen Pharmaceutica and UNICANCER initiates the phase III CARLHA-2 trial in Prostate cancer (Combination therapy) in France (PO) (NCT04181203) (EudraCT2017-000155-21) Updated 05 Feb 2020
31 Dec 2019 Trial Update Dana-Farber Cancer Institute terminates a phase II trial in Prostate cancer (Combination therapy, Hormone refractory) in USA due to safety concerns (PO) (NCT03093272) Updated 06 Apr 2020
13 Dec 2019 Phase Change - Registered Registered for Prostate cancer (Adjunctive treatment, Metastatic disease) in Canada (PO) [6] Updated 18 Dec 2019
12 Dec 2019 Phase Change - Preregistration Preregistration for Prostate cancer (Adjunctive treatment, Metastatic disease) in Canada (PO) [6] Updated 18 Dec 2019
10 Dec 2019 Trial Update Janssen Pharmaceutica and UNICANCER plans the phase III CARLHA-2 trial in Prostate cancer (Combination therapy) in France (PO) (NCT04181203) (EudraCT2017-000155-21) Updated 12 Dec 2019
03 Dec 2019 Trial Update European Organisation for Research and Treatment of Cancer initiates a phase III trial for Prostate cancer in Spain (EudraCT2018-000899-15) Updated 27 Aug 2020
03 Dec 2019 Trial Update European Organisation for Research and Treatment of Cancer initiates a phase III trial for Prostate cancer in Belgium (EudraCT2018-000899-15) Updated 03 Jan 2020
07 Nov 2019 Trial Update Janssen Research & Development initiates a comparison-based phase I pharmacokinetic trial (In volunteers, In patients with hepatic impairment) in USA (PO) (NCT04154774) Updated 19 Dec 2019
06 Nov 2019 Trial Update Janssen Research & Development plans a phase I pharmacokinetic trial (In volunteers) in USA (PO) (NCT04154774) Updated 11 Nov 2019
30 Sep 2019 Scientific Update Efficacy data from a phase III SPARTAN trial in Prostate caner released by Janssen [36] Updated 01 Oct 2019
18 Sep 2019 Phase Change - Marketed Launched for Prostate cancer (Adjunctive treatment, Metastatic disease) in USA (PO) Updated 19 Sep 2019
17 Sep 2019 Phase Change - Registered Registered for Prostate cancer (Adjunctive treatment, Metastatic disease) in USA (PO) [13] Updated 19 Sep 2019
25 Jul 2019 Trial Update Cambridge University Hospitals NHS Foundation Trust and Janssen-Cilag completes a phase II trial for Prostate Cancer in United Kingdom (PO) (NCT03365297) Updated 25 Nov 2019
19 Jul 2019 Trial Update Janssen Research & Development completes the phase I BEDIVERE trial in Prostate Cancer (Combination therapy, Hormone refractory, Metastatic disease) in USA and Canada (PO) (NCT02924766) Updated 07 Aug 2019
11 Jun 2019 Phase Change - III Phase-III clinical trials in Prostate cancer (Neoadjuvant therapy, Late-stage disease, Adjunctive treatment) in Canada, Germany, Netherlands, Spain, United Kingdom, USA (PO, Tablet) (NCT03767244) (EudraCT2018-001746-34) Updated 11 Jul 2019
04 Jun 2019 Phase Change - Preregistration Preregistration for Prostate cancer (Metastatic disease, Hormone-sensitive) in European Union (PO) [19] Updated 11 Jun 2019
31 May 2019 Scientific Update Interim safety and efficacy data from the TITAN phase III trial in Prostate cancer presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019) [48] Updated 16 Jun 2019
31 May 2019 Phase Change - Preregistration Preregistration for Prostate cancer (Metastatic disease, Hormone-sensitive) in Japan (PO) [19] Updated 11 Jun 2019
31 May 2019 Scientific Update Safety and efficacy data from the phase III TITAN trial in Prostate cancer presented at the 55th Annual Meeting of American Society of Clinical Oncology (ASCO-2019) [49] [50] Updated 07 Jun 2019
27 May 2019 Trial Update Janssen Pharmaceutical completes a phase I pharmacokinetic trial in Japan (NCT02162836) Updated 29 Jul 2019
03 May 2019 Scientific Update Efficacy, pharmacokinetics and adverse events data from the phase II NEAR trial in Prostate cancer presented at the 114th Annual Meeting of the American Urological Association (AUA-2019) [76] Updated 31 Dec 2019
30 Apr 2019 Trial Update Janssen completes enrolment in a phase II trial in Prostate cancer (Late-stage disease, Metastatic disease, First-line therapy, Combination therapy) in Brazil (PO) (NCT02867020) [72] Updated 29 Jun 2020
29 Apr 2019 Phase Change - Preregistration Preregistration for Prostate cancer (Adjunctive treatment, Metastatic disease) in USA (PO) [14] Updated 02 May 2019
11 Apr 2019 Trial Update Janssen Research & Development completes the phase I bioavailabiliy trial in healthy volunteers in Belgium (PO) (NCT03802682) Updated 08 May 2019
29 Mar 2019 Scientific Update Safety data from a phase I trial in Prostate cancer presented at the 110th Annual Meeting of the American Association for Cancer Research (AACR-2019) [109] Updated 20 Apr 2019
01 Mar 2019 Trial Update Aragon Pharmaceuticals completes a phase II trial in Prostate cancer (Combination therapy, Second-line therapy or greater) in USA (NCT01790126) Updated 07 Oct 2019
30 Jan 2019 Regulatory Status Janssen announces intention to submit regulatory applications for approval of apalutamide for Prostate cancer in 2019 [51] Updated 04 Jul 2022
24 Jan 2019 Phase Change - II Phase-II clinical trials in Prostate cancer (Combination therapy) in Brazil (PO) (NCT02789878) Updated 08 Feb 2019
21 Jan 2019 Licensing Status Janssen and Nippon Shinyaku agree to co-promote apalutamide in Japan for Prostate cancer (Hormone refractory) [3] Updated 23 Jan 2019
17 Jan 2019 Phase Change - Registered Registered for Prostate cancer (Hormone refractory) in Liechtenstein, Iceland, Norway (PO) [20] Updated 04 Feb 2019
17 Jan 2019 Phase Change - Registered Registered for Prostate cancer (Hormone refractory) in European Union (PO) [20] Updated 18 Jan 2019
17 Jan 2019 Trial Update Janssen Research & Development plans a phase I bioavailability trial in healthy volunteers in Belgium (PO) (NCT03802682) Updated 17 Jan 2019
11 Jan 2019 Trial Update Janssen Research & Development initiates a phase I bioavailability trial in healthy volunteers in Belgium (PO) (NCT03802682) Updated 07 Feb 2019
01 Jan 2019 Trial Update Janssen completes enrolment in its phase II trial for Prostate cancer (Second-line therapy or greater, Combination therapy) in USA (PO) (NCT03279250) Updated 29 Jun 2020
06 Dec 2018 Trial Update Janssen Research & Development plans a phase III trial for Prostate Cancer (Late-stage disease) in USA, Argentina, Australia, Brazil, Canada, China, Czech Republic, France, Germany, Israel, Italy, South Korea, Netherlands, Poland, Spain, Taiwan and United Kingdom , (NCT03767244) Updated 11 Jul 2019
16 Nov 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Adjunctive treatment, Hormone refractory) in Argentina (PO) before November 2018 [118] Updated 23 Nov 2018
16 Nov 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Adjunctive treatment, Hormone refractory) in Brazil (PO) before November 2018 [118] [16] Updated 23 Nov 2018
16 Nov 2018 Phase Change - Registered Registered for Prostate cancer (Adjunctive treatment, Hormone refractory) in Argentina (PO) [118] Updated 23 Nov 2018
16 Nov 2018 Phase Change - Registered Registered for Prostate cancer (Adjunctive treatment, Hormone refractory) in Brazil (PO) [118] [16] Updated 23 Nov 2018
15 Nov 2018 Regulatory Status Committee for Medicinal Products for Human Use (CHMP) recommends approval of Apalutamide for Prostate cancer in European Union [21] Updated 22 Nov 2018
19 Oct 2018 Scientific Update Efficacy, adverse and pharmacokinetics data from the phase III SPARTAN trial in Prostrate cancer presented at the 43rd European Society for Medical Oncology Congress (ESMO-2018) [35] Updated 28 Dec 2018
31 Aug 2018 Phase Change - I Phase-I clinical trials in Prostate cancer (Metastatic disease, Hormone refractory) in China (PO) (NCT03523442) Updated 04 Oct 2018
05 Jul 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Adjunctive treatment, Hormone refractory) in Australia (PO) before July 2018 [15] Updated 23 Nov 2018
05 Jul 2018 Phase Change - Registered Registered for Prostate cancer (Adjunctive treatment, Hormone refractory) in Australia (PO) [15] Updated 23 Nov 2018
04 Jul 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Hormone refractory) in Canada (PO) before July 2018 [7] Updated 06 Jul 2018
04 Jul 2018 Phase Change - Registered Registered for Prostate cancer (Hormone refractory) in Canada (PO) [7] Updated 06 Jul 2018
03 Jul 2018 Phase Change - III Phase-III clinical trials in Prostate cancer (Adjunctive treatment, Hormone refractory) in Colombia (PO) (NCT03523338) Updated 27 Dec 2023
03 Jul 2018 Phase Change - III Phase-III clinical trials in Prostate cancer (Adjunctive treatment, Hormone refractory) in Mexico (PO) (NCT03523338) Updated 27 Dec 2023
03 Jul 2018 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory, Adjunctive treatment) in Brazil (PO) (NCT03523338) Updated 10 Aug 2018
28 Jun 2018 Phase Change - I Phase-I clinical trials in Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in USA, Belgium, Canada, Italy, Netherlands, Russia (PO) (NCT03551782) Updated 11 Mar 2022
28 Jun 2018 Phase Change - I Phase-I clinical trials in Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in Spain (PO) (NCT03551782) Updated 25 Jul 2018
05 Jun 2018 Trial Update Cambridge University Hospitals NHS Foundation Trust and Janssen-Cilag initiates enrolment in a phase II trial for Prostate Cancer in United Kingdom (PO) (NCT03365297) Updated 22 Jun 2018
18 May 2018 Scientific Update Efficacy data from the phase III SPARTAN trial released by Janssen Pharmaceuticals [32] Updated 24 May 2018
14 May 2018 Trial Update Janssen Research & Development plans a phase I trial for Prostate Cancer in China , (NCT03523442) Updated 04 Oct 2018
27 Apr 2018 Trial Update National Cancer Institute initiates enrolment in a phase II trial for Prostate cancer (Metastatic disease, Recurrent) in USA (NCT03371719) Updated 22 Jun 2018
28 Mar 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Hormone refractory) in Japan (PO) [17] Updated 04 Apr 2018
22 Mar 2018 Phase Change - II Phase-II clinical trials in Prostate cancer (Neoadjuvant therapy) in USA (PO) (NCT03412396) Updated 05 Apr 2018
06 Mar 2018 Trial Update Janssen initiates a phase II trial for Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater) in USA (PO) (NCT03360721) Updated 23 Mar 2018
21 Feb 2018 Phase Change - Marketed Launched for Prostate cancer (Hormone refractory) in USA (PO) - First Global Launch [9] Updated 23 Feb 2018
21 Feb 2018 Scientific Update Updated efficacy data from the phase III SPARTAN trial in Prostate cancer released [9] Updated 23 Feb 2018
19 Feb 2018 Trial Update Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute plan a phase II trial for Prostate cancer (Combination therapy, Metastatic disease) in USA, in March 2018 (NCT03436654) Updated 04 Oct 2018
14 Feb 2018 Scientific Update Adverse events data from a phase III SPARTAN trial in Prostate cancer released by Janssen Research & Development [119] Updated 16 Feb 2018
14 Feb 2018 Phase Change - Registered Registered for Prostate cancer (Hormone refractory) in USA (PO) - First global approval [10] Updated 15 Feb 2018
09 Feb 2018 Phase Change - Preregistration Preregistration for Prostate cancer (Hormone refractory) in European Union (PO, Tablet) [22] Updated 19 Feb 2018
08 Feb 2018 Scientific Update Adverse events data from the phase III SPARTAN trial in Prostrate cancer presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU-2018) [34] Updated 15 Feb 2018
08 Feb 2018 Scientific Update Efficacy data from the phase III SPARTAN trial in Prostrate cancer presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU-2018) [33] [34] Updated 14 Feb 2018
26 Jan 2018 Trial Update M.D. Anderson Cancer Center and Janssen plan a phase II trial for Prostate cancer (Neoadjuvant therapy) in the US (NCT03412396) Updated 05 Apr 2018
28 Dec 2017 Trial Update NRG Oncology and National Cancer Institute plan a phase II trial in Prostate cancer (Late-stage disease) in USA in February 2018 (NCT03371719) Updated 22 Jun 2018
21 Dec 2017 Regulatory Status FDA assigns PDUFA action date of 01/04/2018 for apalutamide for non-metastatic castration-resistant Prostate cancer [12] Updated 15 Feb 2018
21 Dec 2017 Regulatory Status Apalutamide receives priority review status for Prostate cancer (Hormone refractory, Second-line therapy or greater) [12] Updated 26 Dec 2017
10 Dec 2017 Trial Update Cambridge University Hospitals NHS Foundation Trust and Janssen-Cilag plans a phase II TAPS01 trial for Prostate cancer (First-line therapy, Newly diagnosed, Metastatic disease) in United Kingdom (EudraCT2017-001700-29) (NCT03365297) Updated 22 Jun 2018
08 Dec 2017 Trial Update M.D. Anderson Cancer Center and Janssen plan a phase II trial for Prostate cancer (Combination therapy, Hormone refractory, Metastatic disease, Second-line therapy or greater), in April 2018 (NCT03360721) Updated 23 Mar 2018
24 Nov 2017 Trial Update Dana-Farber Cancer Institute and Janssen initiates the phase II FORMULA-509 trial for Prostate cancer in USA (NCT03141671) Updated 30 Jan 2018
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Metastatic disease) in Canada (PO, Capsule) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for phase-I development in Prostate-cancer(Hormone refractory, Metastatic disease, Second-line therapy or greater) in Japan (PO, Capsule) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for phase-I development in Prostate-cancer(In volunteers) in USA (PO, Tablet) Updated 04 Nov 2017
02 Nov 2017 Trial Update University of Washington, the National Cancer Institute and Janssen initiate a phase II trial for Prostate cancer in USA (NCT02721979) Updated 30 Jan 2018
13 Oct 2017 Trial Update Janssen initiates enrolment in a phase II trial in Prostate cancer (Second-line therapy or greater, Combination therapy) in USA (PO) (NCT03279250) Updated 01 Nov 2017
11 Oct 2017 Phase Change - II Phase-II clinical trials in Prostate cancer (Late-stage disease, Metastatic disease, First-line therapy, Monotherapy) in Brazil (PO) (NCT02867020) Updated 31 Oct 2017
11 Oct 2017 Trial Update Janssen initiates enrolment in a phase II trial in Prostate cancer (Late-stage disease, Metastatic disease, First-line therapy, Combination therapy) in Brazil (PO) (NCT02867020) Updated 31 Oct 2017
11 Oct 2017 Phase Change - Preregistration Preregistration for Prostate cancer (Hormone refractory, Second-line therapy or greater) in USA (PO) [11] Updated 17 Oct 2017
19 Sep 2017 Trial Update M.D. Anderson Cancer Center plans a phase II trial for Prostate cancer (Combination therapy) in USA (NCT03279250) Updated 08 Dec 2017
10 Jul 2017 Trial Update Janssen and Duke University Medical Center initiate the phase II PANTHER trial for Prostate cancer (Combination therapy) in USA (NCT03098836) Updated 08 Dec 2017
23 Jun 2017 Phase Change - II Phase-II clinical trials in Prostate cancer (Combination therapy, Hormone refractory) in USA (PO) (NCT03093272) Updated 24 Aug 2017
20 Jun 2017 Phase Change - II Phase-II clinical trials in Prostate cancer (Neoadjuvant therapy) in Singapore (PO) (NCT03124433) Updated 21 Nov 2017
06 Jun 2017 Trial Update University of Athens plans a phase II trial for Prostate cancer (Metastatic disease, Late-stage disease) (NCT03173859) Updated 07 Feb 2019
17 May 2017 Regulatory Status Johnson & Johnson Pharmaceuticals announces intention to submit regulatory filings for apalutamide in pre-metastatic Prostate cancer in between 2017 and 2021 Updated 06 Jun 2017
09 May 2017 Trial Update Dana-Farber Cancer Institute and Janssen plan a phase II trial for Prostate cancer (Combination therapy) in USA (NCT03141671) Updated 30 Jan 2018
04 May 2017 Trial Update The National Cancer Institute and University of Washington initiates a phase II trial for Prostate cancer (Combination therapy, Neoadjuvant therapy) in USA (PO) (NCT02849990) Updated 04 May 2017
24 Apr 2017 Trial Update Singapore General Hospital plans a phase II trial for Prostate cancer(Neoadjuvant therapy) (NCT03124433) Updated 21 Nov 2017
06 Apr 2017 Trial Update Duke University Medical Center and Janssen plan the PANTHER phase II trial for Prostate cancer (Metastatic disease, Combination therapy, Treatment-naive, Hormone refractory) (NCT03098836) Updated 08 Dec 2017
03 Apr 2017 Trial Update Dana-Farber Cancer Institute and Janssen plan a phase II trial for Prostate cancer (Combination therapy, Hormone refractory) in USA (NCT03093272) Updated 03 Apr 2017
06 Mar 2017 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, Recurrent, Second-line therapy or greater) in USA (PO) (NCT03009981) Updated 03 Apr 2017
09 Feb 2017 Trial Update Janssen Research & Development completes a phase I pharmacokinetics trial (In volunteers, In adults, In the elderly) in USA (NCT02524717) Updated 04 May 2017
08 Feb 2017 Trial Update Janssen and Institut Paoli Calmettes initiate a phase-II clinical trial in Prostate cancer in France (PO) (EudraCT2016-001266-29) Updated 24 Feb 2017
06 Feb 2017 Phase Change - II Phase-II clinical trials in Prostate cancer (Newly diagnosed, Combination therapy) in USA (PO) before February 2017(NCT02903368) Updated 17 Mar 2017
03 Jan 2017 Trial Update Janssen Research & Development and Alliance Foundation Trials plan a phase III trial for Prostate cancer (Combination therapy, Recurrent, Second-line therapy or greater) in USA (PO, Tablet) (NCT03009981) Updated 09 Jan 2017
16 Dec 2016 Trial Update Instituto do Cancer do Estado de São Paulo and Janssen plan a phase II trial for Prostate cancer (Combination therapy) in Brazil (PO) (NCT02789878) Updated 29 Dec 2016
01 Dec 2016 Trial Update Janssen Pharmaceutical completes a phase I trial in Prostate cancer (In volunteers) in Japan (PO, Tablet) (NCT02835508) Updated 18 Jan 2017
01 Dec 2016 Trial Update Janssen Scientific Affairs and Weill Medical College of Cornell University initiate a phase I trial for Prostate cancer (Combination therapy, Metastatic disease) in USA (PO) (NCT02913196) Updated 29 Dec 2016
30 Nov 2016 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, Late-stage disease) in Argentina, Belgium, Brazil, Canada, Czech Republic, France, Israel, Germany, South Korea, Malaysia, Mexico, Netherlands, Poland, Romania, Russia, Sweden, Taiwan, Turkey, Ukraine and United Kingdom before November 2016 (PO) (NCT02531516) Updated 30 Nov 2016
01 Oct 2016 Phase Change - II Phase-II clinical trials in Prostate cancer (Combination therapy, Neoadjuvant therapy) in USA (PO) (NCT02770391) Updated 29 Dec 2016
01 Oct 2016 Trial Update Janssen Research & Development initiates enrolment in a phase I BEDIVERE trial for Prostate Cancer (Combination therapy, Hormone refractory, Metastatic disease) in USA and Canada (PO) (NCT02924766) Updated 16 Nov 2016
21 Sep 2016 Trial Update Janssen Scientific Affairs and Weill Medical College of Cornell University plan a phase I trial for Prostate cancer (Combination therapy, Metastatic disease) in USA (PO) (NCT02913196) Updated 28 Sep 2016
12 Sep 2016 Trial Update Janssen Scientific Affairs and Dana-Farber Cancer Institute plan a phase II trial for Prostate cancer (Combination therapy, Newly diagnosed) in USA (PO) (NCT02903368) Updated 28 Sep 2016
10 Aug 2016 Trial Update Janssen Pharmaceuticals and Latin American Cooperative Oncology Group plan a phase II trial for Prostate cancer (Late-stage disease, Metastatic disease, First-line therapy, Newly diagnosed, Monotherapy, Combination therapy) in Brazil (PO, Tablet) (NCT02867020) Updated 17 Aug 2016
26 Jul 2016 Trial Update The National Cancer Institute and University of Washington plan a phase II trial for Prostate cancer (Combination therapy, Neoadjuvant therapy) in USA (PO) (NCT02849990) Updated 02 Aug 2016
01 Jun 2016 Phase Change - I Phase-I clinical trials in Prostate cancer (In volunteers) in Japan (PO, Tablet) (NCT02835508) Updated 20 Jul 2016
10 May 2016 Trial Update Case Comprehensive Cancer Center plans a phase II trial for Prostate cancer (Neoadjuvant therapy, Combination therapy) in USA (PO) (NCT02770391) Updated 19 May 2016
01 May 2016 Phase Change - II Phase-II clinical trials in Prostate cancer (Combination therapy, Metastatic disease) in USA (PO) (NCT02703623) Updated 01 Jun 2016
01 May 2016 Trial Update Janssen Pharmaceuticals, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University initiate a phase II trial for Prostate cancer (Combination therapy) in USA (PO) (NCT02772588) Updated 17 May 2016
16 Apr 2016 Scientific Update Pharmacodynamics data from a preclinical trial in Prostate cancer presented at the 107th Annual Meeting of the American Association for Cancer Research (AACR-2016) [120] Updated 26 Apr 2016
22 Mar 2016 Trial Update The National Cancer Institute and University of Washington plan a phase II trial for Prostate cancer in USA and Singapore (PO) (NCT02721979) Updated 31 Mar 2016
22 Mar 2016 Trial Update Janssen Research & Development initiates a drug-interaction and pharmacokinetics phase I trial for Prostate cancer in Spain (NCT02592317) Updated 22 Mar 2016
04 Mar 2016 Trial Update M.D. Anderson Cancer Center plans the phase II DynaMO trial for Prostate cancer (Combination therapy, Metastatic disease, Castration-resistant) in USA (PO) (NCT02703623) Updated 16 Mar 2016
01 Feb 2016 Trial Update Janssen Research & Development completes a drug-interaction and pharmacokinetics phase I trial for Prostate cancer in Spain and Moldova (NCT02592317) Updated 22 Mar 2016
01 Dec 2015 Phase Change - I Phase-I clinical trials in Prostate cancer (Hormone refractory) in Canada (PO) (NCT02578797) Updated 05 Feb 2016
27 Nov 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Adjunctive treatment, Metastatic disease, Newly diagnosed ) in Mexico, Germany, China (PO) (NCT02489318) Updated 30 Oct 2017
19 Nov 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, Late-stage disease) in China (PO) (NCT02531516) Updated 04 Jul 2022
03 Nov 2015 Trial Update Janssen Research & Development plans a drug-interaction and pharmacokinetics phase I trial for Prostate cancer in Moldova (NCT02592317) Updated 03 Nov 2015
01 Nov 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Adjunctive treatment, Metastatic disease, Newly diagnosed ) in Argentina, Czech Republic, France, Israel, Japan, South Korea, Romania, Russia, Turkey and Ukraine after November 2015 (PO) (NCT02489318) Updated 02 Jun 2016
01 Nov 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Adjunctive treatment; Metastatic disease; Newly diagnosed) in United Kingdom, Sweden, Poland, Hungary, Australia, Australia, Spain, Canada, Brazil, USA (PO) (NCT02489318; EudraCT2015-000735-32) Updated 05 Feb 2016
01 Nov 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy) in Spain, USA (PO) Updated 05 Jan 2016
15 Oct 2015 Trial Update Aragon plans a phase I cardiac safety trial in patients with Prostate cancer in USA, Canada, the Netherlands and United Kingdom (NCT02578797) Updated 22 Oct 2015
21 Aug 2015 Trial Update Aragon plans a phase III trial for Prostate cancer in USA, Czech Republic, Israel and Taiwan (NCT02531516) Updated 27 Aug 2015
20 Aug 2015 Trial Update Janssen Research & Development plans a phase I trial (In volunteers, In adults, In the elderly) in USA (NCT02524717) Updated 20 Aug 2015
13 Aug 2015 Trial Update Janssen Research & Development initiates a phase I pharmacokinetics trial (In volunteers, In adults, In the elderly) in USA (NCT02524717) Updated 09 Oct 2015
07 Jul 2015 Trial Update Janssen plans a phase III trial for Prostate cancer (metastatic disease, adjunctive treatment) in USA, Argentina, Brazil, Canada, Germany, Romania and Spain (NCT02489318) Updated 07 Jul 2015
02 Apr 2015 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, First-line therapy, Hormone refractory, Metastatic disease) in Italy (PO) (EudraCT2014-001718-25) [42] Updated 15 Feb 2021
01 Dec 2014 Trial Update Janssen completes a phase I drug-drug interaction trial (In volunteers) in USA (NCT02230033) Updated 02 Jan 2015
01 Nov 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, First-line therapy, Hormone refractory, Metastatic disease) in South Africa, Brazil, Argentina (PO) (NCT02257736) Updated 19 Feb 2018
01 Nov 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, First-line therapy, Hormone refractory, Metastatic disease) in United Kingdom, Germany, Spain, Russia, Netherlands, Mexico, South Korea, Japan, France, Canada, Belgium, Australia (PO) (NCT02257736; EudraCT2014-001718-25) Updated 09 Oct 2015
01 Nov 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (Combination therapy, Hormone-refractory, Metastatic disease, First-line therapy) in USA (PO) (NCT02257736) after November 2014 Updated 02 Jan 2015
01 Nov 2014 Trial Update Janssen completes a phase I trial in Healthy male volunteers in USA (PO, Tablet and Capsule) (NCT02160756) Updated 04 Dec 2014
02 Oct 2014 Trial Update Janssen Research & Development plans a phase III trial for Prostate Cancer (First-line therapy, Combination therapy, Hormone-refractory, Metastatic disease) in USA (NCT02257736) Updated 06 Nov 2014
01 Sep 2014 Trial Update Janssen initiates a phase I drug-drug interaction trial in Healthy volunteers in USA (NCT02230033) Updated 10 Oct 2014
31 Jul 2014 Phase Change - I Phase-I clinical trials in Prostate cancer (Combination therapy, Metastatic disease) in USA & Canada (PO) Updated 11 Sep 2014
16 Jun 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory) in USA, Australia, Austria, Canada, Czech Republic, Belgium, Germany, Denmark, Japan, Italy, Ireland, Israel, France, Finland, Hungary, Poland, New Zealand, Netherlands, Romania, Slovakia, Spain, Sweden, Norway, Russia, South Korea, Taiwan and United Kingdom (PO) (NCT01946204) Updated 04 Apr 2018
16 Jun 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory) in Netherlands, Czech Republic, France, Ireland, United Kingdom (PO, Tablet) (EudraCT 2012-004322-24) Updated 19 Feb 2018
16 Jun 2014 Phase Change - III Phase-III clinical trials in Prostate cancer (castration-resistant; second-line therapy or greater) in Canada, Australia, New Zealand, United Kingdom, Ireland, Czech Republic, France, Netherlands, Norway, Israel, South Korea, Taiwan & Russia (PO) Updated 23 Jun 2014
01 Jun 2014 Trial Update Janssen initiates enrolment in a phase I trial in Healthy male volunteers in USA (PO, Tablet and Capsule) (NCT02160756) Updated 28 Jul 2014
01 Jun 2014 Phase Change - I Phase-I clinical trials in Prostate cancer (metastatic disease, hormone refractory, second-line therapy or greater) in Japan (PO) Updated 25 Jul 2014
03 Apr 2014 Trial Update The Memorial Sloan-Kettering Cancer Center initiates enrolment in a phase Ib trial for Prostate cancer in USA (PO) (NCT02106507) Updated 14 Apr 2014
01 Apr 2014 Trial Update Janssen completes a phase I bioavailability trial in Prostate cancer (in volunteers) in USA (NCT02031666) Updated 25 Jul 2014
01 Dec 2013 Phase Change - I Phase-I clinical trials in Prostate cancer (in volunteers) in USA (PO, Tablet) Updated 20 Jan 2014
11 Oct 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (second-line therapy or greater, hormone-refractory) in USA (PO) Updated 21 Oct 2013
27 Aug 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory) in Austria, Finland, Sweden, Belgium, Germany, Hungary, Denmark, Spain, Poland, Slovakia, Italy (PO, Tablet) (EudraCT 2012-004322-24) Updated 19 Feb 2018
27 Aug 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory) in Italy (PO, Capsule) (EudraCT 2012-004322-24) Updated 19 Feb 2018
27 Aug 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (Hormone refractory) in Slovakia (PO, capsule) (EudraCT 2012-004322-24) Updated 19 Feb 2018
27 Aug 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (hormone-refractory, second-line therapy or greater) in Belgium, Germany, Denmark, Hungary, Spain and Poland after August 2013 (PO) Updated 21 Jan 2014
27 Aug 2013 Phase Change - III Phase-III clinical trials in Prostate cancer (second-line therapy or greater, hormone-refractory) in Austria, Finland and Sweden (PO) Updated 04 Sep 2013
19 Aug 2013 Company Involvement Aragon Pharmaceuticals has been acquired and merged into Johnson & Johnson [1] Updated 26 Aug 2013
07 Aug 2013 Trial Update Phase III trial planned for non-metastatic, castration-resistant Prostate cancer in USA (IRB00009363) Updated 07 Aug 2013
27 Mar 2013 Trial Update Aragon Pharmaceuticals completes enrolment in its phase I trial in Healthy volunteers in Netherlands (NCT01822041) Updated 04 Sep 2013
04 Mar 2013 Trial Update Aragon Pharmaceuticals completes a phase II trial in Prostate cancer (Monotherapy, Second-line therapy or greater) in USA (NCT01790126) Updated 09 Oct 2019
04 Mar 2013 Trial Update Aragon Pharmaceuticals initiates enrolment in a phase II trial for Prostate cancer (Monotherapy, Second-line therapy or greater) in USA (NCT01790126) Updated 09 Oct 2019
04 Mar 2013 Phase Change - II Phase-II clinical trials in Prostate cancer (combination therapy, second-line therapy or greater) in USA (PO) (NCT01790126) Updated 06 Mar 2013
01 Mar 2013 Phase Change - I Phase-I clinical trials in Prostate cancer in Netherlands (PO) Updated 04 Sep 2013
21 Feb 2013 Trial Update Aragon Pharmaceuticals initiates enrolment in a phase Ib trial for Prostate cancer (hormone refractory, metastatic disease, combination therapy, second-line therapy or greater) in USA (NCT01792687) Updated 06 Mar 2013
01 Oct 2012 Scientific Update Efficacy and adverse events data from a phase I/II trial in Prostate cancer presented at the 37th Congress of the European Society of Medical Oncology (ESMO-2012) [86] Updated 04 Oct 2012
06 Mar 2012 Scientific Update Adverse events and preliminary efficacy data from a phase I/II in Prostate cancer presented at the American Society for Clinical Oncology Genitourinary Cancers Symposium (ASCO GCS-2012) [87] Updated 08 Mar 2012
27 Jul 2010 Phase Change - I/II Phase-I/II clinical trials in Prostate cancer (hormone refractory, treatment-naive, late-stage disease) in USA (PO) Updated 11 Aug 2010
20 May 2009 Phase Change - Preclinical Preclinical trials in Prostate cancer in USA (PO) Updated 11 Aug 2010

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  84. Rana McKay R, Xie W, Yang X, Acosta A, Rathkopf DE, Laudone VP, et al. Post radical prostatectomy (RP) PSA outcomes following 6 versus 18 months of perioperative androgen receptor signaling inhibitors (ARSI) in men with localized high-risk prostate cancer: Results of Part 2 of a randomized phase 2 trial. ASCO-GeCS-2024 2024; abstr. 326.

    Available from: URL: https://meetings.asco.org/abstracts-presentations/230329
  85. Aragon Pharmaceuticals Announces Clinical Results from Ongoing Phase II Trial Confirming Robust Anti-Tumor Activity and Tolerability of ARN-509 in Three Different Patient Populations of Castration Resistant Prostate Cancer.

    Media Release
  86. Aragon Pharmaceuticals Secures $42 Million in Series C Financing to Advance Pipeline of Therapies Targeting Hormone-Driven Cancers.

    Media Release
  87. Aragon Pharmaceuticals Doses First Patient in Phase 1/2 Clinical Trial of ARN-509 for Castration-Resistant Prostate Cancer.

    Media Release
  88. An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer

    ctiprofile
  89. A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients Post Abiraterone Acetate

    ctiprofile
  90. Honma Y, Monden N, Yamazaki K, Kano S, Satake H, Kadowaki S, et al. Yatagarasu: A single-arm, open-label, phase 2 study of apalutamide (APA) plus goserelin (GOS) for patients (pts) with far locally advanced or recurrent/metastatic (fLA/RM) and androgen receptor (AR)-expressing salivary gland carcinoma (SGC). ASCO-2022 2022; abstr. 6079.

    Available from: URL: https://meetings.asco.org//abstracts-presentations/207054
  91. An Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Apalutamide in Combination With Gonadotropin-releasing Hormone (GnRH) Agonist in Subjects With Locally Advanced or Recurrent/Metastatic and Androgen Receptor (AR) Expressing Salivary Gland Carcinoma

    ctiprofile
  92. A Single-Dose, Open-Label Study to Evaluate the Pharmacokinetics of Apalutamide in Subjects With Severe Hepatic Impairment Compared With Subjects With Normal Hepatic Function

    ctiprofile
  93. A Randomized, Open-label, Two-way, Crossover Study to Evaluate the Relative Bioavailability of Apalutamide Administered Orally as Whole Tablets and as a Mixture in Applesauce in Healthy Subjects

    ctiprofile
  94. An Open-label, Multicenter, Phase 1b Study of JNJ-63723283, a PD-1 Inhibitor, Administered in Combination With Apalutamide in Subjects With Metastatic Castration-Resistant Prostate Cancer

    ctiprofile
  95. Phase 1b Study of ARN 509 Plus Everolimus in Men With Progressive Metastatic Castration-Resistant Prostate Cancer After Treatment With Abiraterone Acetate

    ctiprofile
  96. A Phase 1 Study of Androgen Receptor (AR) Antagonist Apalutamide in Chinese Subjects With Metastatic Castration-Resistant Prostate Cancer

    ctiprofile
  97. A Safety and Pharmacokinetics Study of Niraparib Plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate Plus Prednisone) in Men With Metastatic Castration-Resistant Prostate Cancer

    ctiprofile
  98. Drug-drug Interaction Study to Evaluate the Effect of Multiple Doses of JNJ-56021927 on the Pharmacokinetics of Multiple Cytochrome P450 and Transporter Substrates in Subjects With Castration-Resistant Prostate Cancer

    ctiprofile
  99. An Open-Label Phase 1b QT/QTc Study of JNJ-56021927 (ARN-509) in Subjects With Castration-Resistant Prostate Cancer

    ctiprofile
  100. A Drug-Drug Interaction, Safety and Efficacy Study With JNJ-56021927 (ARN-509) and Abiraterone Acetate in Subjects With Metastatic Castration-Resistant Prostate Cancer

    ctiprofile
  101. A Phase 1 Study of Androgen Receptor (AR) Antagonist JNJ-56021927 in Subjects With Metastatic Castration-Resistant Prostate Cancer

    ctiprofile
  102. Phase Ib, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Ascending Doses of ARN-509 in Combination With Abiraterone Acetate in Patients With Metastatic Castrate Resistant Prostate Cancer (CRPC)

    ctiprofile
  103. A Single-Dose, Open-Label Study to Evaluate the Pharmacokinetics of JNJ-56021927 in Subjects With Mild or Moderate Hepatic Impairment Compared With Subjects With Normal Hepatic Function

    ctiprofile
  104. A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Pharmacokinetic Profile of JNJ-56021927 When Administered as the Tablet Formulation in Healthy Male Japanese Subjects

    ctiprofile
  105. An Open-Label, Randomized, Parallel-Group Drug-Drug Interaction Study to Assess the Effect of Multiple Doses of Itraconazole or Gemfibrozil on the Pharmacokinetics of a Single Dose of JNJ-56021927 in Healthy Male Subjects

    ctiprofile
  106. A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Relative Bioavailability of 7 Test Tablet Formulations of JNJ-56021927 With Respect to the Capsule Formulation of JNJ-56021927 Under Fasted Conditions in Healthy Male Subjects

    ctiprofile
  107. A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Relative Bioavailability of 3 Tablet Formulations of JNJ-56021927 With Respect to the Capsule Formulation of JNJ-56021927 Under Fasted Conditions in Healthy Male Subjects

    ctiprofile
  108. Molina A, Christos P, Hackett A, Nordquist L, Gelmann E, Stein M, et al. Phase I trial of apalutamide plus abiraterone acetate, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). AACR-2019 2019; abstr. CT097 / 21.

    Available from: URL: http://link.adisinsight.com/t5HBc
  109. A Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

    ctiprofile
  110. Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone Acetate and Apalutamide (ARN-509) for Rising PSA After Radical Prostatectomy With Adverse Features.(FORMULA-509 Trial)

    ctiprofile
  111. The Association Between HSD3B1 Genotype and Steroid Metabolism in Normal and Prostate Cancer Tissue of Men With Intermediate and High-risk Prostate Cancer Undergoing Radical Prostatectomy After Treatment With ARN-509 and Leuprolide

    ctiprofile
  112. A Phase 2 Study of Apalutamide in Active Surveillance Patients

    ctiprofile
  113. A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy

    ctiprofile
  114. Aragon Pharmaceuticals Secures $22 Million in Series B Financing.

    Media Release
  115. JOHNSON & JOHNSON_FORM 10-K. Internet-Doc 2023;.

    Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/200406/000020040623000016/jnj-20230101.htm
  116. Oudard S, Hadaschik BA, Saad F, Cella D, Basch E, Mainwaring PN, et al. Health-related quality of life (HRQoL) at final analysis of the SPARTAN study of apalutamide (APA) vs placebo (PBO) in patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen deprivation therapy (ADT). ESMO-2020 2020; abstr. 632P.

    Available from: URL: https://www.sciencedirect.com/science/article/pii/S0923753420408877
  117. Janssen receives positive CHMP opinion for ERLEADA(Tm) (apalutamide) for patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease.

    Media Release
  118. FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint.

    Media Release
  119. McMullin R, Gupta H, Rajpurohit Y, Nguyen H, Brown L, Sondheim D, et al. Addition of ARN509 and docetaxel, alone or in combination, to castration demonstrates improved efficacy and heterogeneity of molecular response in prostate cancer patient-derived xenografts. AACR-2016 2016; abstr. 3074.

    Available from: URL: http://www.abstractsonline.com/plan/AbstractPrintView.aspx?mID=4017&sKey=1dd5cbb1-93de-438f-91fe-6ef6521ee0ac&cKey=d3578f37-07df-46bb-b4e4-ad3e68050004&mkey=%7b1D10D749-4B6A-4AB3-BCD4-F80FB1922267%7d
  120. Data on Phase III SPARTAN trial of apatamide for nonmetastatic castration-resistant prostate cancer patients - published in ASCO GU 2018 and The New England Journal of Medicine.

    Media Release
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