7508 Background: Data on response to BCMA-targeted therapies among BCMA-exposed pts with RRMM are limited. Outcomes after sequential/subsequent anti-BCMA bispecific T-cell engagers (Bs-TCE) are vital to evaluate. Etentamig is a next-generation differentiated BCMA x CD3 Bs-TCE composed of a bivalent BCMA-binding domain with a high-avidity, low-affinity CD3-binding domain potentially reducing cytokine release syndrome (CRS), and a silenced Fc tail for extended half-life and convenient monthly (Q4W) dosing. Phase 1 results of etentamig in RRMM showed robust efficacy and potential best-in-class safety. Methods: Arm B of the open-label, Phase 1b MOVISO study (NCT05650632) evaluated etentamig in pts with RRMM with ≥2 prior lines of therapy (PLT), including triple-class and prior BCMA exposure (antibody-drug conjugate ADC >30 days or CAR-T >6 months mo after last exposure). Primary safety endpoints were CRS and immune effector cell-associated neurotoxicity syndrome (ICANS); efficacy endpoints included objective response rate (ORR; IMWG 2016), duration of response (DoR), and progression-free survival (PFS). Pts received etentamig (60 mg IV; no step-up dosing SUD) on Cycle 1 Day 1 and Q4W thereafter. Results: At cutoff (June 11, 2025), 41 prior BCMA-exposed pts (CAR-T, n=24; ADC, n=17) had been treated; 24 (57%) were male, 38 (93%) were White, median (mdn) (range) age was 68 (43–89) years, 37 (88%) had ECOG PS ≤1, and 34 (81%) were triple-class refractory. Mdn (range) PLT was 6 (3–15). For 21 (51%) pts, the last PLT was BCMA directed; 23 (56%) had previously responded to anti-BCMA therapy (17/24 71% for CAR-T and 6/17 35% for ADC). Mdn (range) time from last prior CAR-T or ADC to first dose of etentamig was 15 (1–30) and 4 (1–45) mo, respectively. Mdn (range) follow-up was 5.5 (0.2–17.1) mo. Despite no SUD, CRS and ICANS were reported in 24 (57%) and 3 (7%) pts, respectively; all G1/2 events, except 1 G3 ICANS. G3/4 neutropenia and infections were reported in 15 (36%) and 17 (41%) pts, respectively. Efficacy outcomes are detailed in the Table (NE, not estimable). For pts whose last PLT was BCMA directed, MRD negativity (clonoSEQ, 10 –5 ) was seen in 2/3 (67%) evaluable pts, along with robust peak activation and proliferation of CD8+ T cells. Conclusions: Pts treated with etentamig achieved durable responses; rates were higher in pts who received CAR-T as last line. No new safety signals were observed; only low-grade CRS was seen despite no SUD. Clinical trial information: NCT05650632 . All prior BCMA (N=41) Prior BCMA CAR-T (N=24) ORR, n/n (%) 95% CI Overall 17/36 (47) 30–65 11/22 (50) 28–72 BCMA-directed last PLT 11/19 (58) 34–80 7/11 (64) 31–89 Mdn DoR, mo 95% CI, No. of pts Overall 13 7–NE, N=17 13 7–NE, N=11 BCMA-directed last PLT 13 7–NE, N=11 13 7–NE, N=7 Mdn PFS, mo 95% CI, No. of pts Overall 3.4 3–11, N=41 8.3 2–NE, N=24 BCMA-directed last PLT 9.4 2–NE, N=21 9.4 2–NE, N=12
Chhabra et al. (Thu,) studied this question.