(PA-051) Initial Results of a Phase 2 Study to Evaluate Elranatamab (elran) Post-idecabtagene Vicleucel (ide-cel) Consolidation (EPIC) in Patients with Relapsed/refractory Multiple Myeloma (RRMM)

Introduction: Ide-cel demonstrated a median PFS of 8.8 months with deeper responses (≥CR) associated with a longer median PFS of 19 months in the phase 2 KarMMa trial. There is an opportunity to improve the depth and durability of responses with ide-cel. Our hypothesis is that elra consolidation 100 days after ide-cel could re-invigorate polyclonal T cell responses against BCMA-positive MM cells at a point when both cytopenias after CAR-T are commonly resolved and the CAR T-cell population has decreased substantially. The EPIC phase 2 study (NCT06138275) in pts with RRMM who have received ide-cel aims to investigate fixed duration elra as a consolidation therapy (tx) to improve PFS by deepening disease response. We present initial results from the EPIC study.

Methods: This single-arm, non-randomized, prospective phase 2 study (NCT06138275) evaluates elra as consolidative tx in pts ≥18 years with RRMM after ≥2 lines of tx who received ide-cel as standard of care. Pts received fixed duration elra consolidation from Day +100 up to +160 after ide-cel infusion (elra schedule, C1-2: D1, D4 (C1 only), D8, D15, D22; C3-6: D1, D15). IVIG was recommended for serum IgG < 400 mg/dL; HSV/VZV and PJP prophylaxis were required. The primary objective is to evaluate the PFS of elra consolidation in RRMM after tx with ide-cel. Key secondary objectives were to evaluate safety, CR/sCR, DOR, MRD-negative conversion rate, time to MRD-negativity, and rate of sustained MRD-negativity of ≥6 or ≥12 months. Data cutoff date was 5/19/2025.

Results: To date, 12 pts have been enrolled with 3 in screening; 6 pts have completed elra consolidation. Median follow-up was 7 months. Median age was 71 (range 48-82), 50% were female, and 25% had high-risk cytogenetics (del[17p], t[4;14], or t[14;16]). Pts had a median of 3 (range 2-6) prior lines pre-ide-cel. Median number of days between ide-cel and elra was 113 days (range 91-158). Five pts received step-up dosing as an outpatient. One pt has had disease progression with an isolated plasmacytoma (329 days post ide-cel; 219 days after start of elra consolidation) requiring radiation tx without any systemic tx. All are currently alive. Disease response post-ide-cel were: 4 sCR, 2 VGPR, and 6 PR and for the 6 pts who have completed elra were: sCR 5/6 and VGPR 1/6. Five of 6 pts who had completed elra with available MRD were all uMRD6 with MRD conversion in 3/6 pts from uMRD positive to uMRD6. CRS occurred in 42% of pts (5 events in 5 pts, all grade [G] 1). No ICANS occurred. Neutropenia G ≥3 was observed in 4 pts (33%) and anemia G ≥3 in 1 pt (8%) with no G ≥3 thrombocytopenia. Six pts (50%) experienced G ≥3 AEs without attribution (febrile neutropenia [FN], n=1; lung infection, n=1, hypertension, n=1; hypophosphatemia, n=1; neutropenia, n=3) and 1 pt was hospitalized (n=1, FN). Enrollment is ongoing.

Conclusions: Early data suggests that elra consolidation after standard of care ide-cel is feasible and may deepen MRD negativity in pts with RRMM. Updated data will be presented.