Stemline Therapeutics, Inc. has announced another patient death in its ongoing phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML).
The company became aware of this death, in a patient with BPDCN, on January 18.
The cause of death has not been determined, but the patient had developed capillary leak syndrome (CLS), a sometimes fatal and well-documented side effect of SL-401.
There have been 2 other deaths reported in patients with CLS in this trial. One of these deaths occurred in a patient with BPDCN and the other in a patient with AML.
Stemline said this study is ongoing, patient enrollment is ahead of schedule, and patients continue to receive SL-401 in the trial. Timelines for study completion and biologics licensing application submission remain on track.
The fact that CLS is an expected complication of SL-401 administration has been noted in filings with the Securities and Exchange Commission and US Food and Drug Administration (FDA), as well as in the study’s informed consent forms and other information provided to investigators.
Stemline said it has and will continue to report data to the FDA in accordance with the study protocol and applicable regulations. The company plans to provide a clinical and safety update on this cohort when the cohort and data are complete.
SL-410 in 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.
SL-401 is being tested in several clinical trials. Results from the phase 2 trial in BPDCN and AML patients were presented at the 2016 ASH Annual Meeting (abstract 342). However, the presentation only included data on the patients with BPDCN.
The trial 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.
As of October 7, 2016, 32 BPDCN patients had been treated—9 in stage 1 and 23 in stage 2. Nineteen patients received SL-401 as first-line treatment, and 13 had relapsed/refractory disease. (Fourteen patients with relapsed/refractory AML were treated in stage 1.)
Efficacy
Of the 19 first-line BPDCN patients, 16 received the optimal dose (12 μg/kg). The overall response rate was 95% among all first-line patients (18/19) and 100% among those who received the optimal dose (16/16).
The complete response rates were 74% (14/19) and 81% (13/16), respectively. Six patients (all who received the optimal dose) proceeded to transplant (autologous and allogeneic).
All 13 relapsed/refractory BPDCN patients received the optimal dose. The overall response rate was 69% (9/13), and the complete response rate was 31% (4/13). One patient proceeded to allogeneic transplant.
Eleven first-line patients, including the 6 who went on to transplant, have ongoing responses. Six relapsed/refractory patients, including the patient who went on to transplant, have ongoing responses.
Among first-line patients treated at the optimal dose, the median progression-free and overall survival have not been reached. Among relapsed/refractory patients (all of whom were treated at the optimal dose), the median progression-free and overall survival are 8.5 months.
Safety
The most common treatment-related adverse events were transaminase elevation (52%), hypoalbuminemia (39%), chills (31%), pyrexia (27%), nausea (23%), fatigue (23%), peripheral edema (23%), thrombocytopenia (19%), hypotension (19%), weight increase (19%), anemia (19%), decreased appetite (19%), and CLS (19%).
In stage 1, two BPDCN patients had 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.
A second CLS-related death occurred in stage 1 in a patient with relapsed/refractory AML (16 μg/kg).
The other death in a BPDCN patient with CLS was reported after the ASH presentation. Stemline became aware of the death on January 18 and disclosed it to the public on February 2.
