RESULTS FROM ONGOING PHASE 2 REGISTRATION STUDY OF SL-401 IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)
(Abstract release date: 05/19/16)
EHA Library. Pemmaraju N. 06/12/16; 135306; S812
Dr. Naveen Pemmaraju
Contributions
Contributions
Abstract
Abstract: S812
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall C13
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (IL-3R; CD123). IL-3R is overexpressed by many hematologic cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) and multiple myeloma. In a prior Phase 1/2 trial, SL-401 demonstrated clinical activity, including multiple complete responses (CRs), in patients with BPDCN, a highly aggressive malignancy of unmet medical need and poor prognosis. Building on this prior experience, we report herein updated efficacy and safety data from our ongoing SL-401 registration trial in BPDCN.
Aims
This Phase 2 trial is a single-arm, open-label, two-stage study consisting of a lead-in dose escalation (stage 1) and subsequent expansion stage (stage 2) designed to generate safety and efficacy data to support potential registration in BPDCN.
Methods
In stage 1, pts with BPDCN or relapsed/refractory (r/r) AML received SL-401 as a daily IV infusion for up to 5 days (7, 9, 12 or 16 µg/kg/day) every 21 days. In stage 2, pts with BPDCN receive SL-401 at the optimal stage 1 dose and schedule. Response criteria include assessment of skin by modified severity weighted assessment tool (mSWAT), and bone marrow, lymph node and viscera by standard measures. Clinical CR (CRc) is defined as no detectable disease in bone marrow, lymph nodes or viscera with microscopic-only skin disease.
Results
At data cut-off (1/20/16), 48 pts (18 BPDCN; 30 r/r AML) were treated with SL-401. 18 BPDCN pts (9+9 in stages 1&2) received SL-401 (7 µg/kg, n=3 [stage 1]; 12 µg/kg, n=15 [6+9 in stages 1&2]); median age 70 yrs (range 45-82 and 1 compassionate use pt age 15); data on 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. Most common treatment-related AEs (all grades) are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 µg/kg) and gr 4 (12 µg/kg). Safety precautions were developed and successfully implemented to minimize risk of severe CLS. Since adoption, severe CLS has not been observed at doses up to 12 µg/kg. No cumulative side effects were observed over multiple cycles. In stage 1, 12 µg/kg was the maximum tested and recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. An 87% (13/15) overall response rate (ORR) was observed in 15 evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node and viscera. A 100% (10/10) ORR was observed in evaluable first-line BPDCN pts, with 90% (9/10) of pts achieving CR (n=7) or CRc (n=2). A 100% (8/8) ORR was observed in evaluable first-line BPDCN pts treated at the optimal dose (12 μg/kg), and all 8 pts achieved either CR (n=6) or CRc (n=2). 6 of the 8 pts either remain on SL-401 in CR (n=4; duration ongoing at 3+ to 8+ cycles) or were bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles).
Conclusion
SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented. SL-401 is also being developed in additional IL-3R/ CD123+ hematologic malignancies, including AML in CR with minimal residual disease and high-risk MPN.
Session topic: Treatment in Specific AML Subgroups
Keyword(s): Acute leukemia, Clinical data, Clinical trial, Dendritic cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall C13
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (IL-3R; CD123). IL-3R is overexpressed by many hematologic cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) and multiple myeloma. In a prior Phase 1/2 trial, SL-401 demonstrated clinical activity, including multiple complete responses (CRs), in patients with BPDCN, a highly aggressive malignancy of unmet medical need and poor prognosis. Building on this prior experience, we report herein updated efficacy and safety data from our ongoing SL-401 registration trial in BPDCN.
Aims
This Phase 2 trial is a single-arm, open-label, two-stage study consisting of a lead-in dose escalation (stage 1) and subsequent expansion stage (stage 2) designed to generate safety and efficacy data to support potential registration in BPDCN.
Methods
In stage 1, pts with BPDCN or relapsed/refractory (r/r) AML received SL-401 as a daily IV infusion for up to 5 days (7, 9, 12 or 16 µg/kg/day) every 21 days. In stage 2, pts with BPDCN receive SL-401 at the optimal stage 1 dose and schedule. Response criteria include assessment of skin by modified severity weighted assessment tool (mSWAT), and bone marrow, lymph node and viscera by standard measures. Clinical CR (CRc) is defined as no detectable disease in bone marrow, lymph nodes or viscera with microscopic-only skin disease.
Results
At data cut-off (1/20/16), 48 pts (18 BPDCN; 30 r/r AML) were treated with SL-401. 18 BPDCN pts (9+9 in stages 1&2) received SL-401 (7 µg/kg, n=3 [stage 1]; 12 µg/kg, n=15 [6+9 in stages 1&2]); median age 70 yrs (range 45-82 and 1 compassionate use pt age 15); data on 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. Most common treatment-related AEs (all grades) are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 µg/kg) and gr 4 (12 µg/kg). Safety precautions were developed and successfully implemented to minimize risk of severe CLS. Since adoption, severe CLS has not been observed at doses up to 12 µg/kg. No cumulative side effects were observed over multiple cycles. In stage 1, 12 µg/kg was the maximum tested and recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. An 87% (13/15) overall response rate (ORR) was observed in 15 evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node and viscera. A 100% (10/10) ORR was observed in evaluable first-line BPDCN pts, with 90% (9/10) of pts achieving CR (n=7) or CRc (n=2). A 100% (8/8) ORR was observed in evaluable first-line BPDCN pts treated at the optimal dose (12 μg/kg), and all 8 pts achieved either CR (n=6) or CRc (n=2). 6 of the 8 pts either remain on SL-401 in CR (n=4; duration ongoing at 3+ to 8+ cycles) or were bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles).
Conclusion
SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented. SL-401 is also being developed in additional IL-3R/ CD123+ hematologic malignancies, including AML in CR with minimal residual disease and high-risk MPN.
Session topic: Treatment in Specific AML Subgroups
Keyword(s): Acute leukemia, Clinical data, Clinical trial, Dendritic cell
Abstract: S812
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall C13
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (IL-3R; CD123). IL-3R is overexpressed by many hematologic cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) and multiple myeloma. In a prior Phase 1/2 trial, SL-401 demonstrated clinical activity, including multiple complete responses (CRs), in patients with BPDCN, a highly aggressive malignancy of unmet medical need and poor prognosis. Building on this prior experience, we report herein updated efficacy and safety data from our ongoing SL-401 registration trial in BPDCN.
Aims
This Phase 2 trial is a single-arm, open-label, two-stage study consisting of a lead-in dose escalation (stage 1) and subsequent expansion stage (stage 2) designed to generate safety and efficacy data to support potential registration in BPDCN.
Methods
In stage 1, pts with BPDCN or relapsed/refractory (r/r) AML received SL-401 as a daily IV infusion for up to 5 days (7, 9, 12 or 16 µg/kg/day) every 21 days. In stage 2, pts with BPDCN receive SL-401 at the optimal stage 1 dose and schedule. Response criteria include assessment of skin by modified severity weighted assessment tool (mSWAT), and bone marrow, lymph node and viscera by standard measures. Clinical CR (CRc) is defined as no detectable disease in bone marrow, lymph nodes or viscera with microscopic-only skin disease.
Results
At data cut-off (1/20/16), 48 pts (18 BPDCN; 30 r/r AML) were treated with SL-401. 18 BPDCN pts (9+9 in stages 1&2) received SL-401 (7 µg/kg, n=3 [stage 1]; 12 µg/kg, n=15 [6+9 in stages 1&2]); median age 70 yrs (range 45-82 and 1 compassionate use pt age 15); data on 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. Most common treatment-related AEs (all grades) are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 µg/kg) and gr 4 (12 µg/kg). Safety precautions were developed and successfully implemented to minimize risk of severe CLS. Since adoption, severe CLS has not been observed at doses up to 12 µg/kg. No cumulative side effects were observed over multiple cycles. In stage 1, 12 µg/kg was the maximum tested and recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. An 87% (13/15) overall response rate (ORR) was observed in 15 evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node and viscera. A 100% (10/10) ORR was observed in evaluable first-line BPDCN pts, with 90% (9/10) of pts achieving CR (n=7) or CRc (n=2). A 100% (8/8) ORR was observed in evaluable first-line BPDCN pts treated at the optimal dose (12 μg/kg), and all 8 pts achieved either CR (n=6) or CRc (n=2). 6 of the 8 pts either remain on SL-401 in CR (n=4; duration ongoing at 3+ to 8+ cycles) or were bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles).
Conclusion
SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented. SL-401 is also being developed in additional IL-3R/ CD123+ hematologic malignancies, including AML in CR with minimal residual disease and high-risk MPN.
Session topic: Treatment in Specific AML Subgroups
Keyword(s): Acute leukemia, Clinical data, Clinical trial, Dendritic cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall C13
Background
SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (IL-3R; CD123). IL-3R is overexpressed by many hematologic cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) and multiple myeloma. In a prior Phase 1/2 trial, SL-401 demonstrated clinical activity, including multiple complete responses (CRs), in patients with BPDCN, a highly aggressive malignancy of unmet medical need and poor prognosis. Building on this prior experience, we report herein updated efficacy and safety data from our ongoing SL-401 registration trial in BPDCN.
Aims
This Phase 2 trial is a single-arm, open-label, two-stage study consisting of a lead-in dose escalation (stage 1) and subsequent expansion stage (stage 2) designed to generate safety and efficacy data to support potential registration in BPDCN.
Methods
In stage 1, pts with BPDCN or relapsed/refractory (r/r) AML received SL-401 as a daily IV infusion for up to 5 days (7, 9, 12 or 16 µg/kg/day) every 21 days. In stage 2, pts with BPDCN receive SL-401 at the optimal stage 1 dose and schedule. Response criteria include assessment of skin by modified severity weighted assessment tool (mSWAT), and bone marrow, lymph node and viscera by standard measures. Clinical CR (CRc) is defined as no detectable disease in bone marrow, lymph nodes or viscera with microscopic-only skin disease.
Results
At data cut-off (1/20/16), 48 pts (18 BPDCN; 30 r/r AML) were treated with SL-401. 18 BPDCN pts (9+9 in stages 1&2) received SL-401 (7 µg/kg, n=3 [stage 1]; 12 µg/kg, n=15 [6+9 in stages 1&2]); median age 70 yrs (range 45-82 and 1 compassionate use pt age 15); data on 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. Most common treatment-related AEs (all grades) are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 µg/kg) and gr 4 (12 µg/kg). Safety precautions were developed and successfully implemented to minimize risk of severe CLS. Since adoption, severe CLS has not been observed at doses up to 12 µg/kg. No cumulative side effects were observed over multiple cycles. In stage 1, 12 µg/kg was the maximum tested and recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. An 87% (13/15) overall response rate (ORR) was observed in 15 evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node and viscera. A 100% (10/10) ORR was observed in evaluable first-line BPDCN pts, with 90% (9/10) of pts achieving CR (n=7) or CRc (n=2). A 100% (8/8) ORR was observed in evaluable first-line BPDCN pts treated at the optimal dose (12 μg/kg), and all 8 pts achieved either CR (n=6) or CRc (n=2). 6 of the 8 pts either remain on SL-401 in CR (n=4; duration ongoing at 3+ to 8+ cycles) or were bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles).
Conclusion
SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented. SL-401 is also being developed in additional IL-3R/ CD123+ hematologic malignancies, including AML in CR with minimal residual disease and high-risk MPN.
Session topic: Treatment in Specific AML Subgroups
Keyword(s): Acute leukemia, Clinical data, Clinical trial, Dendritic cell
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