ASCO 2026: mRNA-4157/V940 (Intismeran Autogene) 5-Year Data — Personalized mRNA Cancer Vaccine Sustains 49% Reduction in Melanoma Recurrence at 5 Years (JCO)

Five-year follow-up data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial, presented by Moderna and Merck at ASCO 2026 and simultaneously published in the Journal of Clinical Oncology, confirm durable and deepening benefit from the personalized mRNA cancer vaccine intismeran autogene (formerly mRNA-4157/V940) combined with pembrolizumab in high-risk resected stage III/IV melanoma. At a median follow-up of 60.3 months (5 years), the combination sustained a 49% reduction in the risk of recurrence or death versus pembrolizumab alone (HR 0.51, 95% CI 0.294–0.887; p=0.0075), with corresponding 59% reduction in distant metastasis-free survival (DMFS; HR 0.411). Five-year recurrence-free survival rates were 68.8% (intismeran + pembrolizumab) vs. 49.1% (pembrolizumab alone). An exploratory overall survival analysis showed a favorable trend (HR 0.471) favoring the combination, though based on small event numbers (n=14 events) this was not statistically significant. Intismeran autogene is a personalized neoantigen vaccine encoding up to 34 tumor-specific neoantigens identified through whole-exome sequencing of each patient's resected tumor, manufactured in approximately 6 weeks per patient. These 5-year data are the first to demonstrate durable multi-year benefit from any personalized mRNA cancer vaccine in a randomized controlled trial, substantially strengthening the therapeutic case ahead of pivotal Phase 3 results. The INTerpath-001 Phase 3 trial in melanoma is fully enrolled (~1,089 patients) with results anticipated 2026–2029; the INTerpath-009 Phase 3 trial in NSCLC is underway.