The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).
SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.
SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.
The drug is under development by Stemline Therapeutics, Inc.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Phase 2 trial of SL-401
The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).
The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.
At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).
Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).
All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.
The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).
In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.
