On December 13, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel therapeutics for difficult to treat cancers, reported detailed data from its SL-401 pivotal trial in BPDCN, as well as results from other ongoing trials in additional indications, at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held in Atlanta, GA (Press release, Stemline Therapeutics, DEC 13, 2017, View Source [SID1234522625]). Presentations are available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.

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SL-401: Pivotal Trial in BPDCN – Primary endpoint met; Median overall survival (OS) not reached in first-line patients; BLA submission preparation underway

We believe the SL-401 pivotal trial in BPDCN is the largest multicenter prospective study ever conducted in this indication. The trial enrolled 45 BPDCN patients (32 first-line, 13 relapsed/refractory) and consisted of 3 Stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion), and Stage 3 (pivotal, confirmatory)

Key outcomes in Stages 1, 2, and 3 (ASH ’17 data)
– Across all 3 stages, 42 patients received SL-401 at 12 ug/kg/day
– In first-line BPDCN, SL-401 (12 ug/kg/day)
– 90% (26/29) overall response rate (ORR)
– 72% (21/29) rate of CR + CRc + CRi (complete response + clinical CR [CR with residual skin abnormality] + CR with incomplete bone marrow recovery)
– 45% (13/29) of patients were bridged to stem cell transplant (SCT)
– In relapsed/refractory BPDCN, SL-401 (12 ug/kg/day)
– 69% (9/13) ORR
– 38% (5/13) CR + CRc + CRi rate; 1 patient bridged to SCT
– Median overall survival (OS) not reached in first-line BPDCN (Stages 1-2, and 3), SL-401 (12 ug/kg/day)
– 71% 12-month OS in Stages 1 and 2; follow-up ongoing for 12-month OS in Stage 3
– Most common treatment-related adverse events (TRAEs) were: alanine aminotransferase increase (52%), aspartate aminotransferase increase (50%), hypoalbuminemia (50%), and thrombocytopenia (38%). TRAEs included capillary leak syndrome (19%), which was grade 5 in 2.4% (1/42) of BPDCN patients at 12 ug/kg/day, 2.6% (4/153) of all patients across all trials at all doses, and 1.7% (2/119) of patients across all trials at 12 ug/kg/day

Stage 3 pivotal cohort (first-line, 12 ug/kg/day)
– Met its primary endpoint with a 54% (7/13) CR + CRc rate (95% CI: 25.1, 80.8)
– The lower bound of the 95% confidence interval (CI) exceeded the pre-specified rate of 10%
– 77% (10/13) ORR
– 46% (6/13) of patients bridged to SCT

Next steps for BPDCN
– A BLA submission is in preparation
SL-401: Phase 1/2 Trial in myeloproliferative neoplasms (MPN): chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF)

Key outcomes (ASH ’17 data)
– SL-401 Phase 1/2 trial consists of a Stage 1 (lead-in, dose escalation) and Stage 2 (expansion); has enrolled 24 patients
– No dose limiting toxicities (DLT) were identified and a maximum tolerated dose (MTD) was not reached. Most common TRAEs include hypoalbuminemia (33%), thrombocytopenia (33%), and fatigue (29%). Most common TRAEs (grade 3 or higher), include thrombocytopenia (24%) and anemia (19%)
– Durable CR (14+ months) in CMML patient
– 65% (11/17 evaluable) of CMML and MF patients had spleen reductions >25% (range 29% to 100%)
– Durable SD in 4 patients (2 CMML, 2 MF) for 5+ to 8+ months. Three ongoing SD patients enrolled with baseline platelet counts <100,000, including 1 patient platelet count <50,000 are on treatment

Next Steps in MPN
– Continue enrollment and patient follow-up
– Favorable tolerability and preliminary signs of activity support both single agent and combination development strategies, including JAK-inhibitors and hypomethylating agents
SL-401: Phase 1/2 Trial in Acute Myeloid Leukemia (AML) in CR with Minimal Residual Disease (MRD)

Key outcomes (ASH ’17 data)
– SL-401 Phase 1/2 trial consists of Stage 1 (lead-in, dose escalation) and Stage 2 (expansion); has enrolled 16 patients
– No DLTs or MTD identified in Stage 1; Most common TRAEs (Stage 1 and 2) include hypoalbuminemia (44%), ALT increase (38%), AST increase (38%), and thrombocytopenia (38%). Most common TRAEs, grade 3+, include ALT increase (31%), AST increase (25%), and thrombocytopenia (19%). 2 cases (13%) of grade 3 CLS were noted
– Five patients, including one who went to SCT at 3+ months, were relapse-free for at least 5+ months (range 5+ to 14+), including 2 ongoing (8+ months [on SL-401] and 14+ months [SCT])

Next Steps for AML/MRD
– Patients enrolling and being followed for MRD alterations and response duration
– Given preclinical data indicating potential synergies between SL-401 and azacitidine in AML and high-risk MDS, and that a clinical trial is underway assessing that combination in AML, a transition to combination therapy in this indication is under active consideration
Ivan Bergstein, M.D., CEO of Stemline, commented "The remarkable data presented at ASH (Free ASH Whitepaper) from our pivotal trial with SL-401 in BPDCN sets the stage for our upcoming BLA submission and a successful 2018. In conjunction with these efforts, we kicked off our BPDCN disease awareness campaign at ASH (Free ASH Whitepaper), which includes outreach to hematologist-oncologists, dermatologists, and pathologists, including highlighting the BPDCN diagnostic signature triad of CD123, CD4 and CD56 (an easy to remember: 1, 2, 3, 4, 5, 6). We believe this endeavor is critical for the proper and timely diagnosis of BPDCN, a historically underappreciated and underdiagnosed malignancy. Additionally, we and our investigators believe SL-401 is beginning to demonstrate encouraging signs of clinical activity in indications beyond BPDCN, including CMML and MPN, as presented at ASH (Free ASH Whitepaper)."