Merck and Moderna reported median five-year follow-up results from their Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating intismeran autogene (mRNA-4157/V940) in combination with Merck’s anti-PD-1 therapy Keytruda for patients with high-risk stage III/IV melanoma after complete surgical resection. In the preplanned analysis, the combination reduced the risk of recurrence or death by 49% versus Keytruda alone on the trial’s primary endpoint of recurrence-free survival (RFS). This represents sustained clinical benefit compared to prior analyses at approximately two and three years, and safety findings remained consistent with earlier reports. Merck and Moderna plan further data presentations at an upcoming medical meeting, reinforcing the potential of this individualized neoantigen mRNA therapy to enhance post-surgical outcomes in melanoma.

Building on the positive Phase 2b results, Merck and Moderna have fully enrolled the INTerpath-001 Phase 3 adjuvant melanoma trial. Two Phase 3 studies in non-small cell lung cancer—one in completely resected disease and one in resectable disease following neoadjuvant Keytruda plus platinum-based chemotherapy—are currently enrolling patients. Additionally, a Phase 2 adjuvant renal cell carcinoma study has reached full enrollment, while randomized Phase 2 trials in muscle-invasive and non–muscle-invasive bladder cancer, first-line metastatic melanoma and metastatic squamous NSCLC are also underway. These programs reflect Merck’s strategy to expand the application of its checkpoint inhibitor in combination with novel mRNA vaccines across multiple tumor types.

William Blair analysts characterize the five-year update as a positive maintenance of the impressive effect over Keytruda monotherapy, noting this is the first therapy to show added benefit in the post-surgical melanoma setting. Myles Minter points out that adaptive immune responses to intismeran appear to be nearly entirely predictive of tumor control, consistent with previous RFS analyses. These endorsements by leading research firms underscore Wall Street’s growing confidence in the combination’s potential to reshape the adjuvant cancer therapy landscape for Merck.