Merck and Moderna announced positive topline results from the Phase 3 INTerpath-001 trial evaluating intismeran autogene (also known as V940 or mRNA-4157), an individualized mRNA-based neoantigen therapy, in combination with Merck's KEYTRUDA (pembrolizumab) as adjuvant treatment for patients with completely resected stage IIB-IV melanoma.

The trial met its primary endpoint of recurrence-free survival and a key secondary endpoint of distant metastasis-free survival, marking what the companies describe as the first positive Phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer treatment. 

It is also the first Phase 3 study to show a clinically meaningful improvement over KEYTRUDA alone — the current standard-of-care immunotherapy — in the adjuvant melanoma setting. 

At a pre-specified interim analysis, the combination therapy showed statistically significant and clinically meaningful improvements in both endpoints among patients with resected stage IIB, IIC, III or IV cutaneous melanoma who had not previously received systemic therapy.  

The trial will continue to evaluate additional secondary endpoints, including overall survival, per the study protocol. Safety results were consistent with prior studies of the combination, with no new safety signals identified. Full data will be presented at an upcoming international medical meeting and shared with regulators.

Professor Georgina Long, the trial's principal investigator and medical director of Melanoma Institute Australia, called the results a landmark for adjuvant melanoma treatment, noting this is the first Phase 3 study to demonstrate that a therapy built around a patient's individual tumor mutation profile, combined with pembrolizumab, can reduce recurrence or death risk compared to KEYTRUDA alone.  

Dr. Dean Y. Li, president of Merck Research Laboratories, said the findings reinforce the potential for a more personalized approach to cancer care, while Moderna CEO Stéphane Bancel described the results as evidence that a once-aspirational goal — an mRNA treatment tailored to an individual's specific cancer — is becoming reality.

The INTerpath clinical program, jointly run by Merck and Moderna, now spans nine Phase 2 and Phase 3 trials evaluating intismeran in combination with KEYTRUDA and other therapies, as well as a monotherapy, across melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma. 

Additional studies include a Phase 2b trial in adjuvant melanoma and a Phase 1 study in pancreatic, gastric and perioperative lung cancers.

Today's readout builds on earlier Phase 2b data from the same combination, including five-year follow-up results presented at the 2026 ASCO Annual Meeting, which showed a 49% reduction in risk of recurrence or death and a 59% reduction in risk of distant metastasis or death compared to KEYTRUDA alone.