On November 1, 2017 Stemline Therapeutics, Inc. (Nasdaq: STML), a clinical stage biopharmaceutical company developing novel therapeutics for difficult to treat cancers, reported that the pivotal Phase 2 trial of SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN) has met its primary endpoint (Press release, Stemline Therapeutics, NOV 1, 2017, View Source [SID1234521405]). Based on feedback from the U.S. Food and Drug Administration (FDA), Stemline remains on track to begin submission of its Biologics License Application (BLA) in the 4Q17-1Q18 timeframe.

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SL-401 has been granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of BPDCN, and Orphan Drug Designation (ODD) by the FDA and EU for the treatment of patients with BPDCN and acute myeloid leukemia (AML).

Pivotal Trial

The pivotal Phase 2 trial of SL-401 is the largest multicenter prospective study ever conducted in BPDCN. The trial enrolled 45 BPDCN (32 first-line, 13 relapsed/refractory) patients at 7 sites in the U.S. The trial consisted of 3 Stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion), and Stage 3 (pivotal, confirmatory).

Stage 3: Design

Stage 3 of the Phase 2 trial was designed with input from the FDA to provide the pivotal, confirmatory evidence of efficacy of SL-401 in BPDCN. First-line-only BPDCN patients received SL-401 intravenously at 12 mcg/kg/day on days 1-5 of a 21-day cycle. The primary endpoint of Stage 3 was the rate of CR, defined per protocol as CR + CRc + CRi (CR = complete response; CRc = clinical complete response: absence of gross disease with minimal residual skin abnormality; CRi = CR with incomplete hematologic recovery) by investigator assessment. Statistical significance is achieved if the lower bound of the 95% confidence interval (CI) of the primary endpoint exceeds 10%.

Stage 3: Top-Line Results

In Stage 3 of the trial, 13 first-line BPDCN patients were enrolled. Stage 3 met its primary endpoint, with a CR rate of 54% (7/13) (95% CI: 25.1, 80.8). Overall response rate (ORR) was 77% (10/13). 46% (6/13) of patients were bridged to stem cell transplant (SCT) following remission on SL-401. 86% (6/7) of complete responders remain relapse-free at 5+ to 8+ months, ongoing.

All Stages (1, 2, and 3): Top-Line Results

Across all stages, lines, and doses in the trial (n=45 BPDCN patients; 32 first-line, 13 relapsed/refractory), the CR rate was 60% (27/45) and the ORR was 82% (37/45). In first-line patients who received SL-401 at all tested doses (n=32 patients), the CR rate was 69% (22/32) and the ORR was 88% (28/32). 41% (13/32) of first-line patients who received SL-401 at all tested doses have been bridged to SCT following remission on SL-401.



All SL-401 Trials: Top-Line Safety Results

The most common treatment-related adverse events (TRAEs) with SL-401 across BPDCN and other clinical trials (acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and multiple myeloma) (n=148 patients) were hypoalbuminemia (47%), aspartate aminotransferase increase (46%), alanine aminotransferase increase (45%), nausea (28%), and thrombocytopenia (28%). Capillary leak syndrome (CLS), a well-documented side effect, occurred in 19% of patients, of which 2% (3/148) were grade 5, as previously reported.

Andrew A. Lane, M.D., Ph.D., Director of the BPDCN Center at the Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School in Boston, and a co-investigator on the study, commented, “BPDCN is a devastating malignancy for which there are no approved therapies. Due to the increasing awareness around BPDCN and the promise of novel targeted agents such as SL-401, we have built a new BPDCN center at Dana-Farber to focus on this historically poorly understood, yet increasingly appreciated, patient population with unmet need. SL-401 has demonstrated efficacy with meaningful clinical benefit in BPDCN while maintaining a manageable safety profile, particularly notable in this predominantly older population, representing a major advance in the management of BPDCN. Also, given the presence of CD123 on additional aggressive hematologic cancers, we are also exploring SL-401 in combination with other agents in clinical trials of high risk MDS and AML.”

Ivan Bergstein, MD, CEO of Stemline, commented, “The successful completion of the largest prospective clinical trial ever conducted in BPDCN, is a major milestone for Stemline, our investigators, and most importantly, patients and their families. We would like to thank and congratulate all those involved in this groundbreaking trial. We look forward to working closely with regulatory authorities in an effort to provide SL-401 to patients as quickly as possible. In parallel, our commercial team continues to ramp-up activities setting the stage, if SL-401 is approved, for a successful launch.”

Conference Call and Webcast

Stemline Therapeutics will host a conference call and audio webcast this morning, Tuesday, October 31, 2017 at 8:30 AM ET. Interested participants and investors may access the conference call by dialing 844-389-8660 (U.S./Canada) or 478-219-0408 (International) and referencing conference ID: 1686609. An audio webcast can also be accessed via the Investor Relations tab of the Stemline Therapeutics website at View Source

About BPDCN

Please visit www.bpdcninfo.com and the BPDCN awareness booth (#3143) at ASH (Free ASH Whitepaper) 2017