Contributions
Abstract: S457
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:15 - 16:30
Location: Hall A
Background
Isatuximab (ISA) is an anti-CD38 monoclonal antibody, which kills tumor cells via multiple mechanisms. Here, we report preliminary data from the dose-escalation cohorts, and the first 3 patients (pts) of the expansion cohort, of a Phase 1b study of ISA plus Pom/Dex in pts with RRMM (NCT02283775).
Aims
To evaluate combination therapy with ISA plus Pom/Dex in pts with RRMM.
Methods
Pts with RRMM (≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor) were sequentially enrolled to ISA 5, 10, or 20 mg/kg (4 weekly doses, then every 2 wks until disease progression or intolerable toxicity) with Pom 4 mg (Days 1–21) and Dex 40 mg (Days 1, 8, 15, and 22; 20 mg if ≥75 yrs old), in 28-day cycles. An expansion cohort was initiated at ISA 10 mg/kg (plus Pom/Dex) based on preliminary safety, efficacy, and PK data. Primary objective: determine maximum tolerated dose (MTD). All patients were required to provide informed consent.
Results
26 pts were analyzed (5 mg/kg [n=8]; 10 mg/kg [n=12]; 20 mg/kg [n=6]), median age 65 (42–80) yrs. Median 4.0 (2–11) prior treatment regimens, with 20 (77%) pts refractory to prior immunomodulatory drug therapy. At data cut-off (Nov 8, 2016), median duration of ISA treatment was 19.0 wks and 16 pts remained on treatment. 2 pts at 10 mg/kg discontinued therapy due to adverse events (AEs) (grade [Gr] 5 perforated bowel; Gr 3 infusion-associated reaction [IAR]). Dose-limiting toxicities reported in 1 pt at each dose level (Gr 4 neutropenia; Gr 4 neutropenic infection; Gr 3 confusional state), and MTD has not been reached. Most common TEAEs, besides IARs, were fatigue (62%), diarrhea (35%), and dyspnea (31%). Most frequent Gr 3/4 hematologic abnormality (laboratory assessment) was neutropenia (Gr 3, 40%; Gr 4, 52%). Gr 3/4 thrombocytopenia was reported in 8 (32%) pts (Gr 3, 16%; Gr 4, 16%). IARs occurred in 12 (46%) pts (Gr ≥3 in 1 pt); only with 1st infusion in 9/12 pts. 16 (62%) pts achieved at least PR (5, 8, and 3 pts at 5, 10, and 20 mg/kg), including 1 CR, 8 VGPR, and 7 PR. Clinical benefit rate (≥ MR) was 73%. Median time to 1st response, 4.2 wks; median duration of response, 25.6 wks. The PK parameters of ISA were not affected by co-administration with Pom/Dex.
Conclusion
The combination of ISA and Pom/Dex was manageable and clinically active in heavily pretreated RRMM. A Phase III trial of this combination is ongoing.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Monoclonal antibody, Imids, CD38
Abstract: S457
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:15 - 16:30
Location: Hall A
Background
Isatuximab (ISA) is an anti-CD38 monoclonal antibody, which kills tumor cells via multiple mechanisms. Here, we report preliminary data from the dose-escalation cohorts, and the first 3 patients (pts) of the expansion cohort, of a Phase 1b study of ISA plus Pom/Dex in pts with RRMM (NCT02283775).
Aims
To evaluate combination therapy with ISA plus Pom/Dex in pts with RRMM.
Methods
Pts with RRMM (≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor) were sequentially enrolled to ISA 5, 10, or 20 mg/kg (4 weekly doses, then every 2 wks until disease progression or intolerable toxicity) with Pom 4 mg (Days 1–21) and Dex 40 mg (Days 1, 8, 15, and 22; 20 mg if ≥75 yrs old), in 28-day cycles. An expansion cohort was initiated at ISA 10 mg/kg (plus Pom/Dex) based on preliminary safety, efficacy, and PK data. Primary objective: determine maximum tolerated dose (MTD). All patients were required to provide informed consent.
Results
26 pts were analyzed (5 mg/kg [n=8]; 10 mg/kg [n=12]; 20 mg/kg [n=6]), median age 65 (42–80) yrs. Median 4.0 (2–11) prior treatment regimens, with 20 (77%) pts refractory to prior immunomodulatory drug therapy. At data cut-off (Nov 8, 2016), median duration of ISA treatment was 19.0 wks and 16 pts remained on treatment. 2 pts at 10 mg/kg discontinued therapy due to adverse events (AEs) (grade [Gr] 5 perforated bowel; Gr 3 infusion-associated reaction [IAR]). Dose-limiting toxicities reported in 1 pt at each dose level (Gr 4 neutropenia; Gr 4 neutropenic infection; Gr 3 confusional state), and MTD has not been reached. Most common TEAEs, besides IARs, were fatigue (62%), diarrhea (35%), and dyspnea (31%). Most frequent Gr 3/4 hematologic abnormality (laboratory assessment) was neutropenia (Gr 3, 40%; Gr 4, 52%). Gr 3/4 thrombocytopenia was reported in 8 (32%) pts (Gr 3, 16%; Gr 4, 16%). IARs occurred in 12 (46%) pts (Gr ≥3 in 1 pt); only with 1st infusion in 9/12 pts. 16 (62%) pts achieved at least PR (5, 8, and 3 pts at 5, 10, and 20 mg/kg), including 1 CR, 8 VGPR, and 7 PR. Clinical benefit rate (≥ MR) was 73%. Median time to 1st response, 4.2 wks; median duration of response, 25.6 wks. The PK parameters of ISA were not affected by co-administration with Pom/Dex.
Conclusion
The combination of ISA and Pom/Dex was manageable and clinically active in heavily pretreated RRMM. A Phase III trial of this combination is ongoing.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Monoclonal antibody, Imids, CD38