Moderna Doses First Patient in Phase 1/2 Trial of mRNA-2808 in Myeloma

Moderna has dosed the first patient in a Phase 1/2 study of mRNA-2808, an investigational mRNA therapy encoding three T-cell engagers, in relapsed or refractory multiple myeloma, per the company's November 3, 2025 announcement. The open-label, multicenter trial, registered on ClinicalTrials.gov as NCT07116616, is recruiting adults whose disease has progressed after proteasome inhibitor, IMiD and anti-CD38 antibody exposure.

How is the trial designed?

The registry record describes a Phase 1/2, open-label, multicenter study of mRNA-2808 in participants with relapsed or refractory multiple myeloma, with the purpose of evaluating safety and tolerability, per ClinicalTrials.gov. The study started on September 30, 2025, with an estimated primary completion in June 2030. Per the company's announcement, the first dose was administered at SCRI Oncology Partners in Nashville, Tennessee, in collaboration with Sarah Cannon Research Institute.

The dosing schedule reflects the construct's pharmacology: during the first 28-day cycle, mRNA-2808 is administered intravenously weekly, then every two weeks through cycle 12, per the company's announcement. Like other Phase 1/2 oncology first-in-human programs, the design logic runs in ordered steps:

1. Dose escalation establishes a tolerated dose level, with adverse events as the primary lens.
2. An expansion phase tests that dose in more patients to characterize activity signals.
3. Efficacy measures such as response rates are evaluated, but without a randomized comparator at this stage.
4. Results inform whether, and in which combination setting, a registrational Phase 3 is designed.

What makes the construct unusual?

mRNA-2808 is described by the company as a multiplexed therapy that encodes three T-cell engagers targeting three validated myeloma-associated antigens in a single drug product. T-cell engagers work by physically linking T cells to tumor cells; encoding three of them in one mRNA construct is intended to improve efficacy and overcome antigen-escape resistance mechanisms, per the company's framing. Whether multiplexed engagement translates into durable responses in heavily pretreated patients is precisely what the trial exists to measure, and no clinical data have yet been disclosed.

What do Phase 1/2 trials of this type actually tell readers?

The registry listing anchors what is known: the study's stated purpose is safety and tolerability, the population is relapsed or refractory myeloma after the three standard drug classes, and the trial record remains the checkable source for status and sites. A first-patient-dosed milestone marks the transition from preclinical claims to human exposure, not evidence of activity. Readers tracking the program should watch for dose-escalation safety data and any disclosed pharmacodynamic markers of T-cell engagement, and treat response-rate language before expansion data as preliminary.

Program-level context is listed among participating sites in trial directories such as the Mount Sinai trial listing, which republishes the registry description of the study's purpose.