Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma.

BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3-13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 10 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×10 CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3-16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development.