Little know Stemline Therapeutics has just provided the public with an update on the ongoing study of its antibody drug conjugate SL-401. The compound targets CD 123, the interleukin-3 receptor. Stemline is testing SL-401 in various hematological malignancies, most impressive results have so far been shown in BPDCN or blastic plasmacytoid dendritic cell neoplasm. Stemline reports:
The Phase 2 BPDCN data presented at ASH cover 32 evaluable adult BPDCN patients treated with SL-401. Results demonstrated that SL-401 produced a 100% (16/16) overall response rate (ORR), including an 81% (13/16) complete response (CR) rate in first-line BPDCN patients treated at the recommended dose of 12 ug/kg/day and a 95% (18/19) ORR in first-line patients treated at the recommended dose or lower. In relapsed/refractory patients, the ORR was 69% (9/13) with a CR rate of 31% (4/13). See Tables 1 and 2 for a summary of efficacy and safety.
Response duration data continue to appear promising, with 69% (11/16) first-line BPDCN patients treated at 12 ug/kg/day remaining relapse-free (range: 1+ to 20+ months, ongoing). This includes four patients receiving SL-401 therapy (range: 1+ to 15+ months, ongoing), six patients in durable remission from SL-401 who were then successfully bridged to stem cell transplant (SCT) and remain in remission (range: 5+ to 20+ months progression-free after first SL-401 dose), and one additional patient undergoing SCT preparation. In the relapsed/refractory setting, 46% (6/13) patients are relapse-free (range: 1+ to 7+ months). This includes five patients receiving SL-401 therapy (range: 1+ to 4+ months, ongoing) and one patient in durable remission from SL-401 who was then successfully bridged to SCT and remains in remission for approximately 8+ months, ongoing. The median progression-free and overall survival for first-line has not been reached and for relapsed/refractory it is currently 8.5 months.
The company is expected to report on the regulatory path of SL-401 in BPDCN in due course. Given that the compound was awarded breakthrough therapy designation by the FDA, an accelerated approval based on the ongoing study is likely. CD123 seems to garner increasing interest among biopharma companies. Immunogen is eager to bring its CD123 ADC into the clinic, while JnJ is studying the effects of its humanized antibody JNJ-56022473. Cellectis on the other hand is developing a CAR-T approach to target CD123.