DP122 | ELRANATAMAB IN COMBINATION WITH DARATUMUMAB AND LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA NOT ELIGIBLE FOR TRANSPLANT: INITIAL RESULTS FROM MAGNETISMM-6 PART 1

Background. Elranatamab (ELRA), a BCMA-CD3 bispecific antibody, induced deep and durable responses with a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (RRMM). MagnetisMM-6 (NCT05623020) is a phase 3, open-label, randomized study evaluating the efficacy and safety of ELRA combined with lenalidomide (R) ± daratumumab (DARA) (EDR or ER) vs DARA + R + dexamethasone (DRd) in pts with transplant-ineligible (TI) NDMM. Part 1 of the study evaluates the optimal dose of EDR or ER in pts with RRMM or NDMM to determine the recommended phase 3 dose for part 2. Initial results from part 1 dose level G (DLG) are presented. Methods. In DLG, eligible pts had TI (≥65 or <65 yr with comorbidities) NDMM, measurable disease, ECOG ≤2, and adequate liver, renal and bone marrow function. Pts received subcutaneous (SC) ELRA with a priming regimen followed by ELRA 76mg SC every 4 weeks (Q4W) on cycle (C) 1 day (D) 1; DARA 1800mg SC weekly (D1, D8, D15, D22 in C1-C2), every 2 weeks (D1, D15 in C3-C6), and Q4W (D1 in C7+); and oral R 25mg daily on D1-D21 in 28-day cycles. Endpoints assessed in DLG include safety and preliminary efficacy. Results. 37 pts were enrolled in DLG; 34 received EDR. Median age was 75.0 yr (range, 67-83); 37.8% were male; 86.5% were White, 13.5% Asian. Four pts (10.8%) had R-ISS stage III disease, 9 (24.3%) had ≥50% baseline bone marrow plasma cells, 1 (2.7%) had ECOG=2, none had EMD, and 9 (24.3%) were frail per the simplified IMWG frailty score. At data cutoff (DCO, Dec 23, 2024), the median follow-up was 4.6 mo (range, 1.2-6.2); treatment was ongoing in 33 pts. TEAEs were reported in 97.3% (G3/4 94.6%) of pts, hematological TEAEs in 78.4% (G3/4 70.3%), and infections in 64.9% (G3/4 18.9%). The most frequent TEAEs (any grade ≥25% or G3/4 ≥10%) are shown in the Table 1. CRS occurred in 62.2%, all ≤G2; 1 case of G2 ICANS was reported. There was one G5 candida pneumonia. 36 out of 37 pts are responders; 2 pending confirmation as of DCO. Confirmed ORR (95% CI) by investigator was 91.9% (78.1-98.3), 81.1% with ≥VGPR. In pts enrolled ≥4 mos before DCO (n=23), confirmed ORR was 95.7% (78.1-99.9), all with ≥VGPR. Conclusions. In pts with TI NDMM, EDR demonstrated a manageable safety profile consistent with the known toxicities of components. High response rate and early responses were observed. Enrollment in dose level H evaluating the ER combination is ongoing. Updated safety and efficacy data with a longer follow-up will be presented.