On June 04, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the oral presentation of positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, JUN 4, 2016, View Source [SID:1234513081]). The Phase 2 trial results were delivered today by Naveen Pemmaraju, M.D. from the University of Texas MD Anderson Cancer Center, via an oral presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL.

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The data presented at ASCO (Free ASCO Whitepaper) cover 24 BPDCN patients treated with SL-401 (19 evaluable for response, 4 recently treated/efficacy assessment pending, and 1 non-evaluable patient). Results demonstrate that SL-401 produced an 89% (17/19) overall response rate (ORR) in BPDCN, with a 100% (12/12) ORR in first-line patients and a 71% (5/7) ORR in relapsed/refractory patients, including one compassionate use patient (see Table 1). In 12 evaluable first-line patients (all doses), there were 9 complete responses (CR) and 2 clinical complete responses (CRc). CRc is defined as a CR in non-skin affected organs with marked gross clearance of skin lesions and residual microscopic skin disease. In the 10 evaluable first-line patients treated at 12 ug/kg/day, the CR/CRc rate was 100% (8 CR and 2 CRc). In the 7 evaluable relapsed/refractory BPDCN patients, including one treated on a compassionate use basis, the ORR rate was 71%, which included 1 CR and 1 CRc (29% CR/CRc rate) and 3 partial responses (PR).

Response duration data continue to mature and appear promising. 75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day remained relapse-free (1+-13+ months). This includes five patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles), and four patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months after the first dose of SL-401 and 1+-7+ months post-SCT). In the relapse/refractory setting, 43% (3/7) of patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months). Patients are being followed for progression free survival (PFS) and overall survival (OS) which, while early, are both trending favorably.

The most common side effects were transaminitis and hypoalbuminemia (see Table 2), which were both largely transient and not dose limiting. Dosing and safety parameters were developed during the lead-in stage of the study to minimize the risk of severe capillary leak syndrome. Since implementation of these measures, SL-401 at doses of 12 ug/kg/day has demonstrated a manageable safety and tolerability profile. Also, multiple consecutive cycles of SL-401 at 12 ug/kg/day were not associated with cumulative side effects.

Naveen Pemmaraju, M.D., Assistant Professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center (Houston, TX), an investigator on the study, commented, "SL-401’s remarkable results to date suggest the agent could very well emerge as the standard of care for both first-line and relapsed/refractory BPDCN, a devastating disease for which there had previously been no effective therapy. Overall, we continue to see very strong activity with SL-401 in both first line and relapsed/refractory patients, and the safety profile continues to be manageable over increasing patient experience. Notably, we have also been able to successfully bridge several patients to transplant which, for the most part, has not been possible at this frequency with existing therapies." Dr. Pemmaraju continued, "We look forward to working closely with Stemline to bring this promising new agent to patients as quickly as possible in BPDCN and other malignancies."

Andrew A. Lane, M.D., Ph.D., Assistant Professor, Medical Oncology at the Dana-Farber Cancer Institute (Boston, MA), and a co-author on the study, commented, "The SL-401 clinical data in first-line and relapsed/refractory BPDCN continues to demonstrate exciting outcomes in these two underserved patient populations, and represents a promising new option for patients with this devastating disease." Dr. Lane continued, "We are very pleased to be ongoing contributors to this study, and look forward to helping to advance this active agent in both BPDCN and other hematologic malignancies as well."

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are excited by SL-401’s continued robust clinical data in all lines of BPDCN. SL-401 appears to be a potent agent, demonstrating a rapid onset of action and promising response durability, while its tolerability profile makes it well-suited for either long-term use or bridging BPDCN patients to transplant." Dr. Bergstein concluded, "Over the remainder of the year, we will continue to enroll first-line and relapsed/refractory patients in this ongoing trial, ramp up our disease awareness efforts, and advance our ongoing regulatory interactions in order to bring this agent to market as soon as possible in both settings."

The tables below summarize efficacy and safety observed in the Phase 2 potentially pivotal trial in BPDCN. Enrollment is ongoing and additional data will be available throughout 2016.

Table 1. Overview of SL-401 Clinical Activity in BPDCN

Major objective responses

89% (17/19) ORR in BPDCN (all lines/all doses)
4 additional recently-treated patients (2 first-line and 2 R/R) not yet evaluable for response
100% (12/12) ORR in first-line BPDCN (all doses)
100% (10/10) CR/CRc rate in first-line BPDCN (12 ug/kg/day)
71% (5/7) ORR in R/R BPDCN
29% (2/7) CR/CRc rate in R/R BPDCN
Response duration data maturing

75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day were progression-free (1+-13+ months). This includes:
5 patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles); and
4 patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months post-first SL-401 dose; 1+-7+ months post-SCT).
43% (3/7) of R/R BPDCN patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months)
Patients continue to be followed for progression free survival (PFS) and overall survival (OS) and, while early, both are trending favorably

Line of Therapy All lines First-line First-line R/R1
Dose Group All Doses All Doses 12 ug/kg 12 ug/kg
n (total) 242 15 12 9
n (evaluable) 19 12 10 7
ORR 89 % 100 % 100 % 71 %
CR/CRc, n (rate) 13 (68%) 11 (92%) 10 (100%) 2 (29%)
PR 4 1 - 3
n, stem cell transplant
(SCT; auto-SCT n=3; allo-SCT n=1) 4 4 4 -
1Includes one patient treated on a compassionate use basis
2Includes 4 patients were recently treated with SL-401 and response assessment is pending

Source: ASCO (Free ASCO Whitepaper), 2016

Table 2. Overview of SL-401 Safety in BPDCN

Most Common Adverse Events (≥ 15% treatment-related adverse effects, TRAEs)
All Grades (%) Grade ≥ 3 (%)
TRAEs All AEs TRAEs All AEs
Transaminase elevation 61 74 57 61
Hypoalbuminemia 43 48 0 0
Chills 35 39 0 0
Pyrexia 30 48 0 0
Nausea 26 52 0 0
Fatigue 26 43 0 9
Thrombocytopenia 22 22 22 22
Hypotension 22 22 0 0
Weight increased 22 30 0 0
Capillary leak syndrome 22 22 9 9
Anemia 17 30 13 17
Decreased appetite 17 22 0 0
Edema peripheral 17 43 0 0