IMS 2026 | Phase I trial results: dual-targeting BCMA and GPRC5D CAR T-cell therapy in multiple myeloma

So BMS-986453 is an autologous dual targeting of BCMA, GPRC5D, CAR T-cell therapy. The goal of simultaneous targeting of both antigens is to prevent resistance and in theory lead to more deep and durable responses. So this was a phase one multi-center dose-finding study of BMS-986453. This was a cohort of patients who were heavily pre-treated with three or more prior lines of therapy. Prior BCMA and GPRC5D exposure were allowed. Importantly in this study, 60 patients were leukapheresed and 58 patients received lymphodepletion and a one-time infusion of BMS-986453 across dose levels, which range from 25 million to 300 million CAR T-cells. From a dose-limiting toxicity, 19% experienced dose-limiting toxicity, 12% of which were hematologic. Infections occurred in about 50% of patients with 21 having grade 3 or higher events. In terms of adverse events of special interest, including cytokine release syndrome, it did occur across dose levels, but overall it was 78%. Grade 3 or higher was 3%. ICANS was relatively uncommon. Ataxia imbalance disorder did occur in two patients, and both of these were low grade with no grade three or higher events. As is expected with GPRC5D targeting, we did see some on-target off-tumor toxicities targeting the skin, the nails, and the oral cavity. That occurred in approximately 50% of the patients, although reassuringly these were predominantly low-grade. From an efficacy perspective, we saw in the entire cohort, 60% of this cohort was BCMA-exposed patients. The majority of them had received a prior BCMA CAR-T. In terms of BCMA and GPRC5D exposure, represented 17% of the entire cohort, and a third of the patients had high-risk disease. With that being said, in terms of best overall response rate, it was 83% in the overall cohort. 74% had a very good partial response, and 57% a complete response or better. But when focusing at dose level one and dose level two, the best response rates were 95 and 93 percent and complete response rates were 67 and 79 percent. What was really more impressive were the responses in BCMA and GPRC5D naive patients at dose level one and dose level two. Best response rates were 100 percent. 100 percent of patients achieved a very good partial response or better and 88 percent achieved a complete response or better with responses continuing to deepen over time. In the same cohort across dose level one and dose level two, we also saw 100% MRD negativity. So certainly across those levels, we really saw good tolerability with few grade three or higher adverse events and very high efficacy for patients who have had four or more prior lines of therapy. The study is ongoing. We do have a cohort and patients being treated one to three prior lines of therapy in BCMA and GPRC5D naive patients.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.