Contributions
Abstract: S116
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A4
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor-α (CD123), a target expressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other malignancies. BPDCN is a highly aggressive hematologic malignancy with a historical overall survival (OS) of ~8-14 mos from diagnosis. BPDCN has no approved therapies or standard of care, highlighting the need for novel therapeutic approaches. SL-401 was granted Breakthrough Therapy Designation for treatment of BPDCN. Detailed results from the pivotal SL-401 Phase 2 trial in BPDCN will be presented.
Aims
Determine safety and efficacy of SL-401 in patients with BPDCN. Stage 3 was prospectively designed to support potential US registration.
Methods
This pivotal Phase 2 trial of SL-401 is a multicenter, open label, non-randomized, single-arm trial. In Stage 1 (lead-in), first line (1L) and relapsed/refractory (r/r) patients with BPDCN received SL-401 as a daily IV infusion at 7, 9, or 12 mcg/kg/day on days 1-5 of a 21-day cycle. BPDCN patients enrolled in subsequent Stages received SL-401 at the dose determined in Stage 1 (12 mcg/kg). Stage 2 (expansion) enrolled 1L and r/r patients, and Stage 3 (pivotal, confirmatory) enrolled only 1L patients. Enrollment in Stages 1, 2, and 3 has completed.
Results
45 patients with BPDCN (Stages 1 and 2, n=32; Stage 3, n=13) were enrolled at 7 sites. Median age 70 yrs (range, 22-84 yrs); 82% male. In Stage 1, 12 mcg/kg was the highest tested dose for BPDCN. Median follow-up for all 1L patients treated at 12 mcg/kg (n=29) was 8.7 mos (range 0.2-29.1). The most common treatment-related adverse events (TRAEs) at 12 mcg/kg in Stages 1, 2, and 3 (n=42) were transaminitis (52%), hypoalbuminemia (50%), and thrombocytopenia (38%). TRAEs at 12 mcg/kg across BPDCN and other indications (AML, MPN, and MM) (n=114) were hypoalbuminemia (49%), transaminitis (48%), and thrombocytopenia (29%). Capillary leak syndrome (all grades) has been generally manageable and reversible, and occurred at 12 mcg/kg in 19% (8/42) of patients with BPDCN (Stages 1, 2, and 3) and 20% (23/114) of patients across all indications; 0.9% (1/114) and 2% (3/153) of cases resulted in death across all indications at 12 mcg/kg (n=114) and all doses (n=153), respectively. The Stage 3 pivotal cohort met its primary endpoint with a 54% (7/13) rate of CR+CRc (95% CI: 25.1, 80.8). Across Stages 1, 2 and 3, in 1L patients dosed at 12 mcg/kg (n=29), ORR was 90% (26/29; 95% CI: 72.6, 97.8) with a 72% (21/29; 95% CI: 52.8, 87.3) rate of CR+CRc+CRi (CR = complete response; CRc=clinical CR: absence of gross disease with minimal residual skin abnormality; CRi=CR with incomplete hematologic recovery). 45% (13/29) of patients were bridged to stem cell transplant (SCT) (10 allo+3 auto). Median OS not reached in 1L patients in Stages 1-2 or Stage 3. In r/r patients, ORR was 69% (9/13) with a 38% (5/13) rate of CR+CRc+CRi.
Conclusion
This pivotal trial of SL-401 in BPDCN met its primary endpoint. In 1L patients dosed at 12 mcg/kg across all 3 stages, ORR was 90% with a 72% rate of CR+CRc +CRi, with 45% of patients bridged to SCT. Across all 3 Stages, SL-401’s side effect profile remained manageable and consistent over increasing patient exposure and experience. Based on these positive data, a BLA submission is in preparation. SL-401 is being evaluated in other trials (as single agent and in combination) including CMML, MF, high risk MDS, AML, and MM.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): acute leukemia, Clinical data, Clinical Trial
Abstract: S116
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 11:45 - 12:00
Location: Room A4
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor-α (CD123), a target expressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other malignancies. BPDCN is a highly aggressive hematologic malignancy with a historical overall survival (OS) of ~8-14 mos from diagnosis. BPDCN has no approved therapies or standard of care, highlighting the need for novel therapeutic approaches. SL-401 was granted Breakthrough Therapy Designation for treatment of BPDCN. Detailed results from the pivotal SL-401 Phase 2 trial in BPDCN will be presented.
Aims
Determine safety and efficacy of SL-401 in patients with BPDCN. Stage 3 was prospectively designed to support potential US registration.
Methods
This pivotal Phase 2 trial of SL-401 is a multicenter, open label, non-randomized, single-arm trial. In Stage 1 (lead-in), first line (1L) and relapsed/refractory (r/r) patients with BPDCN received SL-401 as a daily IV infusion at 7, 9, or 12 mcg/kg/day on days 1-5 of a 21-day cycle. BPDCN patients enrolled in subsequent Stages received SL-401 at the dose determined in Stage 1 (12 mcg/kg). Stage 2 (expansion) enrolled 1L and r/r patients, and Stage 3 (pivotal, confirmatory) enrolled only 1L patients. Enrollment in Stages 1, 2, and 3 has completed.
Results
45 patients with BPDCN (Stages 1 and 2, n=32; Stage 3, n=13) were enrolled at 7 sites. Median age 70 yrs (range, 22-84 yrs); 82% male. In Stage 1, 12 mcg/kg was the highest tested dose for BPDCN. Median follow-up for all 1L patients treated at 12 mcg/kg (n=29) was 8.7 mos (range 0.2-29.1). The most common treatment-related adverse events (TRAEs) at 12 mcg/kg in Stages 1, 2, and 3 (n=42) were transaminitis (52%), hypoalbuminemia (50%), and thrombocytopenia (38%). TRAEs at 12 mcg/kg across BPDCN and other indications (AML, MPN, and MM) (n=114) were hypoalbuminemia (49%), transaminitis (48%), and thrombocytopenia (29%). Capillary leak syndrome (all grades) has been generally manageable and reversible, and occurred at 12 mcg/kg in 19% (8/42) of patients with BPDCN (Stages 1, 2, and 3) and 20% (23/114) of patients across all indications; 0.9% (1/114) and 2% (3/153) of cases resulted in death across all indications at 12 mcg/kg (n=114) and all doses (n=153), respectively. The Stage 3 pivotal cohort met its primary endpoint with a 54% (7/13) rate of CR+CRc (95% CI: 25.1, 80.8). Across Stages 1, 2 and 3, in 1L patients dosed at 12 mcg/kg (n=29), ORR was 90% (26/29; 95% CI: 72.6, 97.8) with a 72% (21/29; 95% CI: 52.8, 87.3) rate of CR+CRc+CRi (CR = complete response; CRc=clinical CR: absence of gross disease with minimal residual skin abnormality; CRi=CR with incomplete hematologic recovery). 45% (13/29) of patients were bridged to stem cell transplant (SCT) (10 allo+3 auto). Median OS not reached in 1L patients in Stages 1-2 or Stage 3. In r/r patients, ORR was 69% (9/13) with a 38% (5/13) rate of CR+CRc+CRi.
Conclusion
This pivotal trial of SL-401 in BPDCN met its primary endpoint. In 1L patients dosed at 12 mcg/kg across all 3 stages, ORR was 90% with a 72% rate of CR+CRc +CRi, with 45% of patients bridged to SCT. Across all 3 Stages, SL-401’s side effect profile remained manageable and consistent over increasing patient exposure and experience. Based on these positive data, a BLA submission is in preparation. SL-401 is being evaluated in other trials (as single agent and in combination) including CMML, MF, high risk MDS, AML, and MM.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): acute leukemia, Clinical data, Clinical Trial