On June 25, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that it has completed submission of a rolling Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ELZONRISTM (tagraxofusp; SL-401), a potential treatment for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a CD123+ malignancy of unmet medical need for which the agent was awarded Breakthrough Therapy Designation (BTD) (Press release, Stemline Therapeutics, JUN 25, 2018, View Source [SID1234532234]).
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Survival probability in first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3
Ivan Bergstein, M.D., Stemline’s CEO, commented, "The completion of our rolling BLA submission is a major milestone for Stemline and the overall BPDCN patient community. We want to recognize the hard work of our dedicated investigators as well as the entire Stemline team in completing this submission. We also want to especially thank all of the patients and their families who participated in the clinical development program. We are committed to bringing this promising agent to BPDCN patients as rapidly as possible."
BPDCN Efficacy – Stages 1, 2, and 3, ELZONRIS (12mcg/kg/day) (n=42)
The trial of investigational agent, ELZONRIS, in patients with BPDCN was comprised of 3 stages, with Stage 3 serving as the pivotal cohort for confirmation of efficacy. To ensure ongoing access to ELZONRIS, patients with BPDCN are being enrolled in an additional cohort, Stage 4. Stage 3 met its primary endpoint with a CR+CRc (complete response + clinical complete response) rate of 54% (95% CI: 25.1, 80.8). A summary of efficacy results is shown below.
Summary table: Efficacy of ELZONRIS (12mcg/kg/day) in patients with BPDCN (Stages 1, 2 and 3 [n=42])
Line of Therapy First-line Relapsed / Refractory
n 29 13
ORR, n (%) 26 (90%) 9 (69%)
CR+CRc+CRi, n (%) 21 (72%) 5 (38%)
CR 12 1
CRc 7 3
CRi 2 1
PR, n (%) 5 (17%) 4 (31%)
Bridged to SCT, n (%) 13 (45%) 1 (8%)
Abbreviations: ORR=overall response rate; CR=complete response; CRc=clinical CR (CR with minimal residual skin abnormality); CRi=CR with incomplete hematologic recovery; PR=partial response; SCT=stem cell transplant.
Overall Safety
148 patients received ELZONRIS (12mcg/kg/day) across all Stemline-sponsored trials, including in BPDCN, myeloproliferative neoplasms, and acute myeloid leukemia. A summary of safety results is shown below.
Summary table: Safety and tolerability of ELZONRIS (12mcg/kg/day) in all Stemline-sponsored clinical trials (n=148)
Most Common Adverse Events (AEs) (>15% treatment-related AEs, TRAEs)
Preferred Term All Grades, n (%) TRAEs, n (%)
TRAEs All AEs Gr 1-2 Gr 3 Gr 4 Gr 5
ALT increased 65 (43.9%) 80 (54.1%) 31 (20.9%) 34 (23.0%) 0 (0.0%) 0 (0.0%)
AST increased 65 (43.9%) 74 (50.0%) 30 (20.3%) 31 (20.9%) 4 (2.7%) 0 (0.0%)
Hypoalbuminaemia 65 (43.9%) 73 (49.3%) 64 (43.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Thrombocytopenia 39 (26.4%) 48 (32.4%) 7 (4.7%) 8 (5.4%) 24 (16.2%) 0 (0.0%)
Nausea 38 (25.7%) 70 (47.3%) 37 (25.0%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Pyrexia 33 (22.3%) 60 (40.5%) 33 (22.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Fatigue 30 (20.3%) 67 (45.3%) 26 (17.6%) 4 (2.7%) 0 (0.0%) 0 (0.0%)
Weight increased 28 (18.9%) 42 (28.4%) 28 (18.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Chills 26 (17.6%) 40 (27.0%) 25 (16.9%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Capillary leak syndrome (CLS)a 25 (16.9%) 25 (16.9%) 16 (10.8%) 5 (3.4%) 3 (2.0%) 1 (0.7%)
Hypotension 23 (15.5%) 36 (24.3%) 17 (11.5%) 5 (3.4%) 1 (0.7%) 0 (0.0%)
Oedema peripheral 22 (14.9%) 57 (38.5%) 21 (14.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
a0.7% (1/148) for all trials (12mcg/kg/day) and 1.6% (3/182) for all trials (all doses) were grade 5. A myocardial infarction, grade 5, was also reported in a patient who experienced a grade 4 CLS.
Overall Survival (OS)
In first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3, the median OS has not been reached. Median follow up was 13.8 months (range: 0.2-37.4+ months).
About ELZONRISTM (tagraxofusp; SL-401)
ELZONRISTM (tagraxofusp; SL-401) is a novel targeted investigational therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. ELZONRIS has successfully completed a pivotal trial in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an indication for which it was granted Breakthrough Therapy Designation (BTD). A rolling Biologics License Application (BLA) submission has been completed. ELZONRIS is also being evaluated in clinical trials in additional indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and myeloma.