Results
As of May 20, 2024, 31 pts had been enrolled and received BMS-986393; manufacturing was successful for 100%. Median age was 62 years (range 31–78); 68% were male; 68% were White and 19% Black or African American. Overall, 26% had high-risk cytogenetics (del[17p], t[4;14], and/or t[14;16]), 65% had 1q21 gain/amp, and 29% had extramedullary disease. Pts had received a median of 2 prior regimens; 29% had received 3 prior regimens. 52% had received prior stem cell transplantation, 71% anti-CD38 therapy, and 1 pt had a BCMA-targeted therapy. Most (90%) had MM refractory to the most recent regimen; 90% had lenalidomide-refractory, 55% triple-class refractory, and 6% penta-class refractory MM.
All pts experienced a treatment-emergent (TE) adverse event (AE), 84% had grade (G) 3/4 TEAEs; there were no AE-related deaths. Treatment-related (TR) AEs occurred in 97%; 45% had a G3/4 TRAE. Cytokine release syndrome occurred in 84% (all G1/2; all resolved); no pts had macrophage activation syndrome/hemophagocytic lymphohistiocytosis. TR neurologic AEs including immune effector cell-associated neurotoxicity syndrome (ICANS), and other select neurotoxicities were observed. ICANS occurred in 10% of pts (all G1/2; all resolved). Other select neurotoxicity was reported in 1 pt (3%; G2 TR ataxia). In addition, 2 pts had low-grade TR dizziness that was transient, of short duration, and required no intervention. On-target/off-tumor nail, skin and oral TRAEs were reported in 29%, 23% and 39% of pts, respectively (all G1/2). On-target/off-tumor TEAEs resolved in 7 of 19 pts overall, with a median duration of 58 days. One pt experienced TR weight loss (G1/2), and TE infections occurred in 12 (39%) pts (all G1/2).
After a median 5.9 months follow-up (range, 3.8–12.1 months) for 24 efficacy evaluable pts, ORR was maintained at 96% and CRR at 46%; 78% of responses (18/23) were still ongoing. Considering disease characteristics, ORR was 100% in pts with high-risk cytogenetics (7/7), 93% for triple-class refractory disease (13/14), and 100% for extramedullary disease (6/6). Of 5 pts with minimal residual disease (MRD) data and a CR or better, 100% were MRD‑negative (10−5 depth; at any time point within 3 months prior to achieving CR or better, until the time of progression or death). PK analyses showed fast and robust cellular expansion with a median time to peak transgene level of 14 days and a peak transgene level comparable to that seen in heavily pretreated pts. Longitudinal assessment of soluble BCMA levels suggested that BMS-986393 infusion caused deep tumor clearance.
Conclusions: A single administration of the GPRC5D-targeted CAR T therapy, BMS-986393, at the RP2D in pts with RRMM and 1–3 prior lines of therapy was well-tolerated and led to a high rate of response that deepened over time, with little early relapse. While follow-up was limited, the safety profile was favorable with no new signals. Notably, the frequency and grade of infections was improved over some BCMA-targeted therapies. These data support BMS-986393 as a potential early-line treatment in RRMM. The trial is ongoing and a further update with longer follow-up will be presented.
