Merck and Moderna's Phase 3 INTerpath-001 Trial Meets Primary Endpoint — First Randomized Phase 3 Confirmation That a Personalized mRNA Cancer Vaccine Works

Merck and Moderna announced that the Phase 3 INTerpath-001 trial of intismeran autogene (mRNA-4157/V940), a personalized neoantigen mRNA cancer vaccine, plus Keytruda (pembrolizumab) met its primary endpoint of recurrence-free survival (RFS) and key secondary endpoint of distant metastasis-free survival (DMFS) versus Keytruda alone, in 1,137 patients with completely resected stage IIB-IV cutaneous melanoma. The companies called the improvements "statistically significant and clinically meaningful" but did not disclose specific hazard ratios or percentage risk reductions, saying detailed data will be presented at an upcoming medical meeting; no new safety signals were observed. INTerpath-001 is the first randomized Phase 3 trial ever designed to definitively prove the benefit of a personalized neoantigen vaccine, following earlier positive Phase 2b KEYNOTE-942 data (49% RFS risk reduction, 59% DMFS risk reduction at 5-year follow-up) that the FDA had previously declined to accelerate-approve on. The vaccine targets up to 34 patient-specific tumor-associated antigens. Merck and Moderna said they now plan to engage regulators on a filing submission, with larger trials already underway in non-small cell lung cancer and mid-stage studies in bladder, kidney, pancreatic, and stomach cancers.