ASCO 2026 | A Phase I/II study of mRNA-2808, a multiplexed T-cell engager, in patients with R/R multiple myeloma

So at this year’s ASCO 2026 meeting, I’m presenting a poster describing a trial in progress, a first in human phase one study of mRNA2808 in patients with relapsed/refractory multiple myeloma. So we know that bispecific antibodies in multiple myeloma have been transformative with really unprecedented efficacy that we’re seeing this patient population. However, a major mechanism of resistance that has emerged is antigen escape. So essentially, loss of mutation of the surface antigen, either BCMA, GPRC5D, or FcRH5, on the plasma cell, which renders resistance to these therapies. So to this end, mRNA2808 was developed. This is an in vivo mRNA-based liponanoprotein multiplex T-cell engager. It encodes three distinct bispecific T-cell antibodies targeting GPRC5D, BCMA, and FcRH5. And the rationale of this approach is that through multi-antigen targeting, you might be able to overcome this resistance mechanism of antigen escape. And so the key eligibility criteria for this particular study are patients with relapsed/refractory multiple myeloma, triple-class exposed, and the patient must be progressing on their last line of therapy or triple-class refractory. Notably, patients who have been exposed to prior BCMA, GPRC5D, or FcRH5-based targeted therapies are eligible for this study. And patients initially receive mRNA2808 weekly for the first four weeks, then every other week thereafter for a fixed duration of 12 cycles. But there’s an option to de-escalate to every four weeks after cycle five. And so to date, we see no dose-limiting toxicities through dose level four. The trial is ongoing across multiple sites across the United States, and we’re looking forward to the continued progress of the study as it matures.

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