Merck, Moderna cancer vaccine clears Phase 3 milestone in melanoma

Merck and Moderna have reported positive Phase 3 results for an investigational cancer treatment that combines an individualised mRNA therapy with Merck’s KEYTRUDA, marking a significant clinical milestone for personalised cancer treatment.

The companies said the INTerpath-001 trial met both its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma. The companies described it as the first positive Phase 3 readout for an individualised neoantigen therapy and an mRNA-based cancer therapy.

“This is the first Phase 3 study to show that intismeran, a treatment designed based on the unique mutational ‘fingerprint’ of a patient's own tumor, given in combination with pembrolizumab can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to KEYTRUDA alone,” said Professor Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia.

The trial compared intismeran autogene, also known as V940 or mRNA-4157, in combination with KEYTRUDA against KEYTRUDA alone. At a pre-specified interim analysis, the combination showed statistically significant and clinically meaningful improvements in both RFS and DMFS among patients whose melanoma had been completely removed through surgery. The study will continue to assess other endpoints, including overall survival.

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The treatment is designed around the genetic characteristics of an individual patient's tumour. Intismeran uses a tumour sample to identify its unique mutations and creates a synthetic mRNA therapy encoding up to 34 neoantigens. The aim is to train the patient's immune system to recognise and attack cancer cells carrying those tumour-specific markers.

The global Phase 3 trial enrolled 1,137 patients with high-risk, resected cutaneous melanoma. Patients were randomised in a 2:1 ratio to receive either intismeran plus KEYTRUDA or KEYTRUDA alone. The treatment was administered after complete surgical resection, with intismeran given every three weeks for up to nine doses and KEYTRUDA every six weeks for approximately one year.

For Merck, the results add another potential application for KEYTRUDA, which is already an established treatment in melanoma. The company is also pursuing a broader strategy of testing cancer medicines earlier in the course of disease, with more than 30 ongoing registrational studies across multiple cancer types and earlier-stage settings.

For Moderna, the trial represents an important test of whether its mRNA technology can move into oncology. The companies are jointly developing intismeran across a wider clinical programme, which currently includes nine Phase 2 and Phase 3 studies covering melanoma, non-small-cell lung cancer, bladder cancer and renal cell carcinoma. Other studies are also evaluating the therapy in pancreatic, gastric and lung cancers.

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“These Phase 3 findings represent a pivotal moment for the field of cancer research. For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality,” said Stéphane Bancel, CEO of Moderna.

The latest results build on earlier Phase 2b findings. Five-year follow-up data presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting showed a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death with the combination compared with KEYTRUDA alone.

“By intervening earlier in the course of disease, when many cancers are considered most treatable, the goal of adjuvant therapy given after surgery is to increase the possibility of cure for more patients,” said Dr Dean Y. Li, president, Merck Research Laboratories. “These first Phase 3 findings for intismeran in combination with KEYTRUDA as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment.”

The companies said the safety profile of the combination in INTerpath-001 was consistent with previously reported studies, with no new safety signals observed. They plan to present the detailed data at an upcoming international medical meeting and engage with regulators on potential filing submissions for intismeran in combination with KEYTRUDA.

The next stage will be regulatory review. While the topline results establish that the trial met its key efficacy endpoints, detailed data—including the magnitude of benefit and the overall-survival outcome—are still to come. The trial will continue to assess overall survival and other secondary endpoints.

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