As of May 24, 2022, 21 pts enrolled and 17 pts received BMS-986393 at doses of 25 (n = 5), 75 (n = 9), and 150 (n = 3) × 106 CAR T cells. Among treated pts, 8 (47%) pts had high-risk cytogenetics (del[17p], t[4;14], and/or t[14;16]) and 8 (47%) pts had extramedullary plasmacytomas. Seven (41%) pts received prior BCMA-targeted therapies, including 6 (35%) pts treated with BCMA-directed CAR T cell therapy (Table). Four (24%) pts had penta-refractory MM.
Grade 3/4 treatment-emergent adverse events related to BMS-986393 (TRAEs) were reported in 11/17 (65%) pts; of these, the most frequent were neutropenia (41%) and thrombocytopenia (35%). TRAEs consistent with on-target, off-tumor activity affecting the skin (18%) and nails (12%), as well as dysgeusia/dysphagia (12%) were reported, all grade 1. Dose-limiting toxicities of prolonged (out to day 42) neutropenia and/or thrombocytopenia were reported in 2 pts; MTD has not been exceeded. Cytokine release syndrome (CRS) was reported in 11/17 (65%) pts, all grade 1/2 (median onset, day 3 [range, 2–4]; median duration, 2 days). Immune effector cell–associated neurotoxicity syndrome (ICANS)–type neurotoxicity was reported in 2/17 (12%) pts, both grade 1 (duration, 1–3 days), and was reversible with steroid treatment (Table).
Responses were reported in 12 of 14 pts evaluable for initial (1‑month) clinical response (overall response rate, 86%), including in 4/6 and 3/5 pts treated with prior BCMA‑directed and BCMA-directed CAR T cell therapies, respectively. Median duration of response has not been reached for any dose level, with median follow-up of 4.0 months (range, 1.0–13.1; Table).At the time of analysis, 15/17 (88%) pts remained in follow-up; 2 (12%) pts discontinued due to progressive disease.
In preliminary pharmacodynamic analyses, greater reductions in soluble BCMA levels were associated with increasing dose from 25 to 75 × 106 CAR T cells, and all 3 pts with complete response (CR) at the 25 × 106 CAR T-cell dose level were minimal residual disease (MRD)–negative (10−5 depth) at month 3, with follow-up ongoing.
Preliminary cellular pharmacokinetic analyses demonstrated a dose-dependent increase in BMS-986393 exposure
