Moderna-Merck mRNA-4157 Vaccine Shows 42% Recurrence Reduction in Phase 2 Melanoma Trial

The randomized phase 2b study enrolled 157 patients with resected stage IIIB-IV melanoma. After surgery, participants received either the individualized neoantigen vaccine plus pembrolizumab or pembrolizumab monotherapy. The primary endpoint was recurrence-free survival; secondary endpoints included distant metastasis-free survival and safety. Vaccine manufacturing averaged eight weeks per patient using tumor sequencing to select up to 34 neoantigens.

Three-year recurrence-free survival reached 74.8% in the combination arm versus 55.6% with checkpoint inhibitor alone, corresponding to a hazard ratio of 0.58. Distant metastasis-free survival improved similarly. Grade 3-4 adverse events occurred at comparable rates, though vaccine-related injection-site reactions and transient systemic symptoms were more frequent. These data build on the 2023 interim readout and align with patterns seen in other neoantigen platforms.

The result strengthens the rationale for mRNA vaccines across tumor types with high mutational burden, yet questions remain about durability beyond three years, scalability of manufacturing, and activity in PD-1-refractory disease. A phase 3 trial is ongoing.

This phase 2b design can demonstrate signals but cannot yet establish overall survival benefit or generalizability; the ongoing phase 3 trial must confirm these findings with larger enrollment and longer follow-up.