Personalized mRNA cancer vaccine scores first phase 3 win in resected melanoma

Clinical takeaway: In patients with completely resected stage IIB-IV melanoma, adding the personalized mRNA neoantigen therapy intismeran autogene (V940/mRNA-4157) to pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus pembrolizumab alone, with no new safety signals reported.

In the phase 3 INTerpath-001 trial, Merck and Moderna announced that intismeran autogene plus pembrolizumab met the study's primary endpoint of RFS and key secondary endpoint of DMFS in 1,137 patients with completely resected stage IIB, IIC, III, or IV melanoma.

The findings are potentially practice-changing because pembrolizumab is a current adjuvant standard of care, yet many patients remain at risk for recurrence after surgery. The combination is the first regimen to demonstrate a clinically meaningful phase 3 improvement over adjuvant pembrolizumab alone and the first positive phase 3 study of an individualized neoantigen therapy or mRNA-based cancer treatment.

Intismeran autogene is manufactured using each patient's tumor-specific mutation profile to generate a personalized anti-tumor immune response. If approved, this approach could establish a new adjuvant treatment paradigm that extends the benefits of precision medicine beyond targeted therapies and into personalized cancer immunotherapy.

“Today's results represent a landmark moment for adjuvant melanoma treatment,” said principal investigator Georgina Long, MD. “Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”

The study remains ongoing, with overall survival still being evaluated. Merck and Moderna plan to present detailed results at an upcoming medical meeting and engage regulators regarding potential filing submissions.

Source: Merck & Moderna. (2026 Aug 19). Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA® Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma