One of the most significant studies presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid marks a milestone in melanoma treatment: a therapeutic cancer vaccine has, for the first time, delivered positive results in a Phase 3 trial, demonstrating significant benefits.

The vaccine, intismeran autogene, developed by Moderna and MSD, was administered in combination with the immunotherapy drug pembrolizumab to patients with surgically removed stage IIB–IV melanoma. After two years, the combination reduced the risk of recurrence by 42% and the risk of distant metastasis by 38%.

These are the main findings of the INTerpath-001 study, presented at the ESMO Congress before an audience of 40,000 oncology professionals from around the world. The results are expected to be published in The New England Journal of Medicine.

The trial enrolled patients with stage IIB–IV cutaneous melanoma whose tumors had been completely removed through surgery, but who remained at significant risk of relapse. Participants were randomly assigned to receive either pembrolizumab combined with the personalized vaccine or pembrolizumab with a placebo.

After a median follow-up of 24.6 months, the vaccine-immunotherapy combination showed a significant benefit in both recurrence-free survival and distant metastasis-free survival. The findings are particularly important because melanoma can return even after a tumor has been completely removed, especially in patients with more aggressive forms of the disease.

Italy played a leading role in the research, enrolling more patients than any other country. The National Cancer Institute in Milan, in particular, recruited more participants than any other center worldwide.

Close collaboration among oncologists, surgeons, pathologists, molecular biologists and pharmacists was crucial to the study’s success. Producing a personalized vaccine requires a complex process: researchers need an adequate tumor sample, analyze its genetic characteristics and identify the relevant neoantigens before manufacturing the vaccine. The entire process takes about six weeks.

“This is a tailor-made vaccine, built around each patient and their tumor,” said Michele Del Vecchio, head of Medical Oncology for Melanoma at the IRCCS National Cancer Institute Foundation in Milan. “Immunotherapy removes the ‘brakes’ that the tumor puts on the immune response, while the vaccine activates an immune response specifically directed against that particular tumor. It also creates an ‘immunological memory’ that helps protect patients against any microscopic clusters of tumor cells left behind after surgery.”

“Intismeran autogene is a therapeutic vaccine designed around the molecular characteristics of each patient’s tumor,” said Paola Queirolo, Coordinator of the multihospital network for melanoma, skin cancers and cancer immunotherapy at the IRCCS AOM in Genoa. “The goal is to stimulate an immune response capable of recognizing any remaining tumor cells and maintaining long-term immune memory against the same antigens.”

The treatment involves nine intramuscular doses of the vaccine as part of a therapeutic regimen that also includes pembrolizumab immunotherapy.

Following the encouraging results in melanoma, additional studies are underway to investigate the vaccine’s potential against other cancers, including pancreatic, lung and bladder cancer.