In December 2020, Gruppo Italiano Malattie EMatologiche dell'Adulto initiated a phase II AML2020 trial to evaluate tagraxofusp in patients with CD123+ or with balstic plasmacytoid dendritic cell neoplasm immunophenotype-like acute myeoid leukaemia (EudraCT2020-001543-94; NCT04342962). The non-randomised, open label trial will enrol approximately 50 participants in Italy  .
In January 2019, Stemline Therapeutics announced that tagraxofusp is commercially available in the US for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and paediatric patients, aged ≥ 2 years, in both treatment-naïve and previously-treated populations  . The approval for the same was granted in December 2018 by the US FDA. The approval is based on the data from STML-401-0114 study [see below]  . The BLA was accepted in August 2018 by the US FDA and granted Priority Review. PDUFA date of February 21, 2019, was assigned to the drug   . The rolling BLA submission was initiated in April 2018, and completed in June 2018  . In January 2017, Stemline Therapeutics entered into an agreement with the US FDA on the registration pathway for tagraxofusp in BPDCN   .
In January 2021, Menarini Group announced that the European Commission (EC) has granted a marketing authorization for tagraxofusp, as monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)  . Earlier in November 2020, the Menarini Group, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion on the approval of tagraxofusp as monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). The positive opinion from the CHMP was based on the largest prospective clinical trial [see below] ever conducted in patients with treatment-naïve or previously-treated BPDCN  . In July 2020, the CHMP adopted negative opinions recommending the refusal of marketing authorisations for tagraxofusp for the treatment of blastic plasmacytoid dendritic cell neoplasm. The submission of the marketing authorization application (MAA) for the same to the European Medicines Agency (EMA) was done in January 2019  . Previously, in July 2019, The EMA issued Day 120 List of Questions (LoQ) related to chemistry, manufacturing and controls (CMC), quality, non-clinical, and all stages of the clinical trial, including stage 4 involving lyophilised drug product to Stemline Therapeutics. Based on the LoQ, the company requested and received a clock stop extension and also requested a scientific advisory group meeting    . In November 2018, European Medicines Agency (EMA) has granted accelerated assessment for the upcoming centralised Marketing Authorization Application (MAA), for tagraxofusp in blastic plasmacytoid dendritic cell neoplasm  . In May 2018, Stemline announced that the company expects feedback from the EMA regarding potential regulatory filing in Europe  .
In August 2019, Stemline Therapeutics reorted establishment of a global Early Access Program (EAP), under which tagraxofusp (ELZONRIS) will be available before approval and outside of the ongoing clinical trials for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN)  .
The Centers for Medicare and Medicaid Services (CMS) assigned a specific and permanent reimbursement J-code for tagraxofusp following the approval. The code became effective on October 1, 2019  . In August 2019, the Centers for Medicare & Medicaid Services (CMS) granted approval for a new technology add-on payment (NTAP) for tagraxofusp for the treatment of adult and paediatric patients, two years and older, with BPDCN  . The on October 2019.
In August 2016, Stemline Therapeutics submitted the that the US FDA had granted breakthrough therapy designation to tagraxofusp for the treatment of BPDCN. The designation was granted on the basis of positive efficacy and safety data from the phase II trial evaluating tagraxofusp in BPDCN patients in both the first-line and relapsed/refractory settings 
Stemline received orphan drug designations for tagraxofusp for the treatment of BPDCN in the US in June 2013 and in the EU, in November 2015   .
The EMA and US FDA granted orphan drug designation to tagraxofusp, for the treatment of AML, in September 2015 and March 2011 respectively  
In October 2017, Stemline Therapeutics released efficacy data stating that the primary endpoint was met in a pivotal phase II trial of tagraxofusp in 47 blastic plasmacytoid dendritic cell neoplasm (BPDCN) (STML-401-0114; NCT02113982). The trial has been completed. Also, in October 2017, Stemline released pooled safety data of tagraxofusp in acute myeloid leukaemia, BPDCN, myeloproliferative neoplasms, and multiple myeloma. In June 2017, the company reported updated clinical data from stages 1 and 2 of the study. In December 2016, the company presented positive safety and efficacy data from the phase II portion of the trial at the 58th Annual Meeting of American Society of Haematology (ASH-2016). In June 2016, Stemline presented data from the phase II part of the phase I/II study at the American Society of Clinical Oncology (ASCO-2016). In December 2015, the company presented positive safety and efficacy data from the lead-in expansion stage of the trial at the 57th Annual Meeting and Exposition of the American Society of Haematology (ASH-Hem-2015). In May 2015, Stemline Therapeutics reported positive clinical results from the trial. Updated safety and efficacy data from the trial were released in December 2017. The open-label, non-randomised phase I/II trial was initiated in September 2014 and consists of separate dose-escalation and dose-expansion parts. In June 2020, updated safety and efficacy data were presented at the 25th Congress of the European Haematology Association (EHA-2020). In June 2021, updated results were presented at the 26th Congress of the European Haematology Association (EHA-2021)                      ..
In December 2014, Stemline Therapeutics initiated a phase I/II trial in IL-3R expressing myeloproliferative neoplasms including mastocytosis, hypereosinophilic syndrome, myelofibrosis (MF) and chronic myelomonocytic leukaemia (CMML) (STML401-0314; NCT02268253). Enrolment of approximately 100 patients, with advanced myeloproliferative neoplasms, is underway in the US and Canada. The company plans to expand the trial to two parts Stage 3 with addition of a single-arm cohorts of patients with previously-treated chronic myelomonocytic leukaemia later in 2019. In the first part of Stage 3 (Stage 3a), enrichment strategies and certain efficacy endpoints, including spleen size reduction and bone marrow complete response with partial hematologic recovery will be assessed. In the second part (Stage 3b), the efficacy endpoints will be confirmed with primary evidences of efficacy to support future registration. In December 2018, Stemline Therapeutics presented the efficacy and safety data at the 60th Annual Meeting and Exposition of the American Society of Haematology (ASH Hem-2018). Later, in May 2019, updated data was presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019). In June 2019, results were presented at the 24th Congress of the European Haematology Association (EHA-2019). Further results were presented at the 25th Congress of the European Haematology Association (EHA - 2020)                    . As of January 2020, enrollment is ongoing for stage 3a cohort including of two patient populations- the relapsed/refractory patients, and first-line, poor prognosis patients not expected to benefit from first line cytoreductive treatment. The myelofibrosis cohort has been expanded to include 20-25 additional patients   . In December 2019, Stemline Therapeutics presented updated safety and efficacy data from the trial at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem 2019). Results showed that tagraxofusp demonstrated single agent clinical activity, with a predictable and manageable safety profile, in patients with relapsed/refractory MF, including in patients with monocytosis   . In December 2020, updated results from the trial were presented at 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2020)  .
In December 2019, Stemline Therapeutics completed a registrational phase I/II trial that evaluated the efficacy and tolerability of tagraxofusp, as a consolidation therapy, in patients with late-stage acute myeloid leukaemia, who are in the first complete remission with minimum residual disease (MRD) following chemotherapy and high risk of relapse (STML401-0214; NCT02270463). The trial was initiated in February 2015 and enrolled 16 participants in the US    . Results from the trial demonstrating that the maximum tolerated dose was not reached were presented at the 58th Annual Meeting and Exposition of the American Society of Haematology (ASH-Hem-2016). Updated safety data were released in December 2017     .
A phase I/II study of single-agent, intravenous tagraxofusp was completed in July 2014 at the Scott & White Cancer Institute and M. D. Anderson Cancer Center (NCT00397579)   . The trial enrolled 91 adult or elderly patients with relapsed, refractory, or poor-risk AML or MDS at sites in Canada and the US. Tagraxofusp was well tolerated at clinically active doses and showed antitumour activity in patients with AML, MDS as well as in patients with BPDCN. Stemline reported in November 2012 that a heavily pretreated patient with refractory and recurrent BPDCN achieved a complete response following treatment with tagraxofusp. The complete response was recorded 30 days after treatment with five daily doses of tagraxofusp. There were no serious adverse events observed     . Later, in January 2013, the company reported that a second heavily pretreated patient with refractory and recurrent BPCDN had achieved a complete response after a single cycle of tagraxofusp  .
Stemline Therapeutics, in December 2019, completed a phase I/II trial, that assessed the safety and efficacy of tagraxofusp in combination with pomalidomide [see Adis Insight drug profile 800016607] and dexamethasone in patients with relapsed or refractory multiple myeloma (NCT02661022; STML-401-0414). The open-label trial was initiated in January 2016, and enrolled nine patients in the US  . In December results from the trial were presented at the 61st American Society of Haematology (ASH-2019)  .
In March 2020, Stemline Therapeutics initiated a phase I/II trial to evaluate tagraxofusp as a maintenance therapy post-stem cell transplant (SCT) in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)  .
Stemline is also planning several trials in other malignancies and uncommon stem-cell derived myeloproliferative disorders  . Stemline Therapeutics plans to initiate clinical trials of tagraxofusp in combination with other therapies  .
In June 2017, Dana-Farber Cancer Institute in collaboration with Stemline Therapeutics initiated a phase I/II study to evaluate the maximum tolerated dose and safety of tagraxofusp in combination with azacitidine and venetoclax in patients with relapsed/refractory acute myeloid lukaemia, treatment-naïve AML not eligible for standard therapy and patients with high risk myelodysplastic syndrome (NCT03113643, 17-056). The open-label study intends to enrol approximately 36 patients in the US  .
Results presented in December 2013 at the 55th Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2013) showed an overall response rate of 86% in the eight patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) that had been treated with a single, 5-day cycle of tagraxofusp  . In December 2014, preclinical results of tagraxofusp were presented for hairy cell leukaemia, myeloproliferative neoplasms and myeloma. Tagraxofusp was shown to block plasmacytoid dendritic cell-triggered growth of myeloma cells, inhibit the development of osteoclasts responsible for bone resorption in myeloma patients, and limit the viability of cancer stem cell-like multiple myeloma cells  .
In a multicentre phase I dose-escalation study, tagraxofusp demonstrated anticancer activity at tolerable doses in patients with relapsed, refractory, or poor-risk AML  .
In November 2019, Stemline Therapeutics presented preclinical data at the 83rd American College of Rheumatology and the 54th Association of Rheumatology Health Professionals Annual Scientific Meeting 
In June 2019, Stemline Therapeutics released preclinical data for tagraxofusp. Preclinical data demonstrated the activity of tagraxofusp against potentially pathogenic plasmacytoid dendritic cells (pDCs). Tagraxofusp inhibited inflammatory pDCs at concentrations that were lower than peak plasma concentrations observed in BPDCN patients treated with the drug  .
In June 2018, Stemline Therapeutics released preclinical data of tagraxofusp at the 19th Annual Congress of the European League Against Rheumatism (EULAR-2018)   .
In December 2017, Stemline reported that resistance to tagraxofusp in AML and BPDCN was associated with loss of the diphthamide synthesis pathway enzyme DPH 1 and could be reversed with azacitidine  .
In December 2019, pharmacodynamics data for tagraxofusp in primary patient MPN peripheral blood mononuclear cells with myelofibrosis and tagraxofusp alone or in combination with ruxolitinib [see Adis Insight Drug profile800026694] in leukaemia was presented at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2019) by Stemline Therapeutics  .
The combination of tagraxofusp and the tyrosine kinase inhibitor ITKI) imatinib (Gleevec®) showed a significant synergistic effect on the primary CML cell growth inhibition in vitro. Additionally, tagraxofusp prolonged the survival of mice inoculated with primary CML cells from patients in blast crisis, including those resistant to several TKIs  .
Stemline Therapeutics reported results from preclinical studies in combination with SL 801 [see Adis Insight drug profile 800023286] in haematological malignancies at the 58th Annual Meeting and Exposition of the American Society of Haematology (ASH-2016)  .
Preclinical study of tagraxofusp in combination with SL 801 is underway against multiple myeloma and haematological malignancies  .
In December 2011, Stemline announced data from two preclinical studies with tagraxofusp showing activity against various lymphoid malignancies. In one of those studies, tagraxofusp inhibited the growth of several Hodgkin's lymphoma cell lines and was active against mantle cell lymphoma, non-Hodgkin's lymphoma, and T-cell acute lymphoblastic leukaemia cell lines. In another study, tagraxofusp demonstrated cytotoxicity against primary tumour cells obtained from patients with BPDCN  . Positive preclinical data for tagraxofusp in CML have been reported  . Preclinical efficacy data in multiple myeloma were reported in May 2014. The studies were conducted in collaboration with Dana-Farber Cancer Institute  .
In August 2019, Stemline Therapeutics announced receipt of regulatory clearance for a phase I/II trial for tagraxofusp as a maintenance therapy post-stem cell transplant (SCT) in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)  .
In August 2019, Stemline Therapeutics announced the pricing of an underwritten public offering of 5 000 000 shares of its common stock at a price of $US15.25 per share, with expected gross proceeds to Stemline of $US76 250 000. Stemline has also granted the underwriters a 30-day option to purchase up to 750 000 additional shares of its common stock at the public offering price, less underwriting discounts and commissions. The offering is expected to close on or about August 13, 2019, subject to customary closing conditions. Stemline will be using the net proceeds from this offering for commercial activities of tagraxofusp, clinical trials for additional indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukaemia (AML), and potentially other diseases such as certain lymphomas, clinical development of additional pipeline candidates (felezonexor, SL 1001, SL 901 and SL 701), research and development and regulatory activities, potential acquisitions and in-licensing; and other general corporate purposes  .
In January 2019, Stemline Therapeutics reported completion of an underwritten public offering of 10 222 222 shares of its common stock and closed gross proceeds of US$92 million. The proceeds from the offering will be utilised for commercial activities of tagraxofusp (SL 401) and its clinical trials in additional indications including chronic myelomonocytic leukaemia (CMML), myelofibrosis (MF) and other diseases, for clinical development of SL 801, SL 701 and potentially SL 901 [see Adis Insight drug profiles 800023286, 800033745 and 800053796], for research and development activities and for potential acquisitions and in-licensing  .
In January 2018, Stemline Therapeutics completed an underwritten public offering of 4 255 000 shares of its common stock and closed gross proceeds of $US59.5 million. The net proceeds will be used for the clinical, regulatory, manufacturing and potential commercial activities of tagraxofusp, for clinical development of SL 801 and SL 701 [see Adis Insight drug profiles and 800033745], for research and development activities, for potential acquisitions and in-licensing, for other general corporate purposes    .
In January 2017, Stemline Therapeutics reported underwritten public offering of $US45 million of its common stock. The net proceeds will be used for the clinical, regulatory, manufacturing and, if and when approved, potential commercial activities of tagraxofusp  .
Stemline completed an equity offering of common stock in January 2015, for net proceeds of approximately $US68 million. The company intends to use the proceeds from the offering to support the clinical development of its lead clinical candidates, including tagraxofusp, and also for other general corporate purposes   .
In May 2013, Stemline Therapeutics priced an underwritten public offering of its common stock to a total gross proceeds of $US60 million. The company plans to use the net proceeds to support development of its clinical drug candidates, including tagraxofusp, and also for other general corporate purposes  .
Stemline completed an initial public offering of common stock in January 2013, for net proceeds of approximately $US32.5 million. Funds were to be used in part to advance development of tagraxofusp  .
The US approved label for tagraxofusp carries a black box warning regarding the increased risk of capillary leak syndrome  .