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<sup>6</sup> CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×10<sup>6</sup> 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.

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Publication Details

Journal
Leukemia
Published
2025-02-05
DOI
https://doi.org/10.1038/s41375-025-02518-5
Citations
6
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
6.27
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article

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

P. Leif Bergsagel, Luciano J. Costa, Lisa M. Kelly, Shaji Kunnathu Kumar et al.
6 citations
Leukemia
CAR-T cell therapy research
6.27
article

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

P. Leif Bergsagel, Luciano J. Costa, Lisa M. Kelly, Shaji Kunnathu Kumar, Jerill Thorpe, Ashley K. Koegel, Alison Maier, Shebli Atrash, Shambavi Richard, Kristen Hege, Gurbakhash Kaur, Benjamin Avi Derman, Sham Mailankody, Michael R. Burgess, Garnet Navarro, Sharmila Das, Philip McCarthy, Michaela Liedtke, Thomas Ly, Divya Varun, Alok Shrestha, Gayathri Ravi
article en
6 citations

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<sup>6</sup> CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×10<sup>6</sup> 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.

LeukemiaVol. 39(4)
Roswell Park Comprehensive Cancer Center (US), Mount Sinai Health System (US), Memorial Sloan Kettering Cancer Center (US), University of Alabama at Birmingham (US), University of Illinois Chicago (US), University of Chicago (US), Bristol-Myers Squibb (United States) (US), Southwestern Medical Center (US), Levine Cancer Institute (US), Mayo Clinic in Arizona (US), Southwestern Medical Center (US), The University of Texas Southwestern Medical Center (US), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 4%
CAR-T cell therapy research
6.27
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