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
Gayathri Ravi, Shambavi Richard, Shaji Kumar, Shebli Atrash, Michaela Liedtke, Gurbakhash Kaur, Benjamin A. Derman, P. Leif Bergsagel, Sham Mailankody, Philip McCarthy, Alok Shrestha, Lisa M. Kelly, Thomas Ly, Sharmila Das, Jerill Thorpe, Alison Maier, Divya Varun, Garnet Navarro, Michael R. Burgess, Kristen Hege, Ashley K. Koegel, Luciano J. Costa
Abstract
Abstract 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 6 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×10 6 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.