MM-071 Subcutaneous (SC) Isatuximab (Isa) Administration by an On-Body Delivery System (OBDS) in Combination With Pomalidomide-Dexamethasone (Pd) in Relapsed/Refractory Multiple Myeloma (RRMM) Patients: Interim Phase 1b Study Results

Abstract

SC Isa delivery would optimize convenience of administration. Prior results showed SC Isa administered by syringe pump has efficacy and safety profiles comparable to IV Isa; recommended Phase 2 dose (RP2D) 1400 mg (IMW21 P-207). Evaluate safety, pharmacokinetics (PK), and efficacy of SC vs IV Isa+Pd Design: Multicenter Phase 1b study. RRMM patients after ≥2 prior treatment lines. Patients randomized 2:1 to SC1000mg or IV10mg/kg and to SC1400mg or IV. Expansion cohort was implemented with SC Isa administered at RP2D via OBDS (wearable bolus injector applied to abdomen). Primary endpoints were safety, including injection site (IS) reactions (ISRs), and PK. 56 patients were randomized and treated: 12 IV, 12 SC1000, 10 SC1400, 22 OBDS. At study entry, ISS stage II-III: IV 67%, SC1000 33%, SC1400 60%, OBDS 50%. On January 20th, 2022, 33% IV, 25% SC1000, 50% SC1400, 86% OBDS patients remained on treatment. Due to sequential accrual, median follow-up (FU; in mo) was longer in IV (20.6) and SC1000 (23.8) than SC1400 (18.1) and OBDS (6.5). Infusion reactions (IRs) were infrequent (≤10% in each cohort, Grade [G] 2), at first IV/SC infusion/injection, with no IRs in OBDS. Local tolerability of OBDS was very good; 5 (22.7%) patients experienced 7 ISR episodes, (G1) of 305 administrations (2.3%): 5 IS erythemas, 1 IS hemorrhage, 1 IS induration. Median duration of OBDS was 10 min. Lower percentage of ≥G3 treatment-related adverse events in OBDS (77%) vs other cohorts (≥80%) may be due to shorter FU. Overall response rate: IV and SC1000 66.7%, SC1400 80.0%, OBDS 77.3%, SC1400+OBDS 78.1%; ≥very good partial response ranged between 40%-50%, complete response 13-25%, partial response 16-40% across cohorts; longer FU is needed for OBDS. Median PFS was: IV 22 mo, SC1000 12.5 mo, SC1400 and OBDS not reached. PK and CD38 receptor occupancy in OBDS were consistent with SC1400. SC Isa via OBDS shows safety profile consistent with IV; with no IRs and excellent tolerability. Efficacy in SC cohorts was comparable to Phase 3 ICARIA. Isa SC administration by OBDS is well-tolerated, requires a short injection duration, and provides a handsfree option.