Five‑year interim data from a Phase II trial combining personalized mRNA neoantigen therapy (intismeran autogene/mRNA‑4157) with pembrolizumab show a 49% reduction in melanoma recurrence and deaths versus control. The open‑label study by Moderna and Merck enrolled resectable high‑risk melanoma patients and used individualized LNP‑delivered mRNA encoding up to 34 neoantigens per patient. The results reinforce the potential of personalized cancer vaccines in the adjuvant setting and provide a pivotal efficacy signal that could inform larger trials. Sponsors will need to address manufacturing scale-up, turnaround time for individualized products, and integration with checkpoint inhibitors to move toward registrational strategies.