Personalized mRNA Vaccine Cuts Melanoma Recurrence Risk by 42% in Phase 3 Trial

Australian researchers have reported that a personalized mRNA vaccine reduced the risk of melanoma returning or causing death by 42% in a large phase 3 trial. The vaccine, created by Moderna and Merck, was tested in more than 1,100 patients at 157 sites worldwide and was given alongside the checkpoint inhibitor pembrolizumab (Keytruda).

"These findings are a foundational shift in our approach to cancer: harnessing the immune system in a more personalized way to reduce the risk of melanoma recurrence or death," said Georgina Long, medical oncologist at Melanoma Institute Australia and global principal investigator of the study.

Long explained that each patient’s tumor DNA is sequenced to identify unique neoantigens, which are then encoded into an mRNA vaccine. The vaccine prompts the patient’s own cells to display these neoantigens, training the immune system to recognize and attack residual cancer cells.

"Cancer can fool the immune system with a fake friendly handshake, so the immune system thinks the cancer cell is normal. Pembrolizumab blocks the handshake, allowing immune cells to recognize the cancer and attack it," Long added.

The trial’s results, presented at the European Society for Medical Oncology Congress 2026 and slated for publication in the New England Journal of Medicine, also showed a 58% risk reduction for patients who remained cancer-free six months after starting treatment. The vaccine is not yet approved in Australia or the United States and will undergo regulatory review.

Experts not involved in the study, such as Robert Vonderheide, president-elect of the American Association for Cancer Research, described the findings as among the field’s biggest breakthroughs. The researchers noted that while similar mRNA vaccine trials for other cancers have not succeeded, this result could pave the way for broader applications of personalized neoantigen therapy.