P945: subcutaneous isatuximab administration by an on-body delivery system in combination with pomalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: interim phase 1b study results

Background: Intravenous (IV) isatuximab (Isa) + pomalidomide-dexamethasone (Pd) is approved for the treatment of relapsed/refractory multiple myeloma (RRMM) patients (pts). Subcutaneous (SC) delivery would optimize convenience of administration. Prior results showed that SC Isa administered by syringe pump has efficacy and safety profiles comparable to IV Isa; the recommended Phase 2 dose (RP2D) was 1400 mg (IMW21 P-207). Aims: This multicenter Phase 1b study evaluated safety, pharmacokinetics (PK), and efficacy of SC vs IV Isa + Pd in RRMM pts after ≥2 prior treatment lines. Methods: Pts were randomized 2:1 to SC1000 mg or IV 10 mg/kg and to SC1400 mg or IV. An expansion cohort was later implemented with SC Isa administered at the RP2D via on-body delivery system (OBDS), a wearable bolus injector applied to the abdomen by a healthcare professional. Primary endpoints (EPs) were safety, including injection site reactions (ISRs), and PK. Main secondary EPs were overall response rate (ORR) and progression-free survival (PFS). Results: Fifty-six pts were randomized and treated: 12 Isa IV, 12 Isa SC1000, 10 Isa SC1400, and 22 OBDS pts. At study entry, ISS stage II–III was 67% in IV, 33% in SC1000, 60% in SC1400, and 50% in OBDS pts. On Jan 20, 2022, 33% IV, 25% SC1000, 50% SC1400, and 86% OBDS pts remained on treatment. Due to sequential accrual, median follow-up (FU) was longer in IV (20.6 mo) and SC1000 (23.8 mo) than SC1400 (18.1 mo) and OBDS (6.5 mo) pts. Infusion reactions (IRs) were infrequent (≤10% in each cohort, all Grade [G] 2), only at first IV or SC infusion/injection, with no IRs in OBDS. Local tolerability of OBDS was very good, with 5 (22.7%) pts experiencing 7 ISR episodes, all G1, out of 305 administrations (2.3%): 5 injection site erythemas, 1 injection site hemorrhage, and 1 injection site induration. Median duration of OBDS injection was 10 min. Incidence of G4 neutropenia was lower in SC1000 (42%) vs the other cohorts (55–60%). The lower percentage of ≥G3 treatment-related adverse events in OBDS (77%) vs the other cohorts (≥80%) may be due to shorter FU. Best overall responses are shown in table; longer FU is needed for OBDS pts. Median PFS was 22 mo in IV, 12.5 mo in SC1000, and not reached in SC1400 and OBDS pts. PK and CD38 receptor occupancy results in OBDS pts are consistent with those observed in SC1400 with pump. Image:Summary/Conclusion: SC Isa administered by OBDS shows a safety profile consistent with IV administration with no IRs and excellent local tolerability. Efficacy in the SC cohorts was comparable to the Phase 3 ICARIA results. Isa SC administration by OBDS is well tolerated, requires a short duration of injection, and provides a convenient hands-free option. Clinical trial information: NCT04045795. Research Sponsor: Sanofi.