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).
Main outcome measure:
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.
MM; Phase I; monoclonal antibody; relapsed/refractory multiple myeloma; subcutaneous.