Intismeran autogene + pembrolizumab sustains 5-year RFS/DMFS benefit in resected melanoma

Intismeran autogene, also known as V940 or mRNA-4157, is Moderna/Merck’s individualized neoantigen mRNA therapy encoding up to 34 patient-specific tumor neoantigens, designed to broaden tumor-specific T-cell responses when combined with PD-1 blockade. In the randomized Phase IIb KEYNOTE-942 trial (NCT03897881), patients with completely resected high-risk stage IIIB–IV cutaneous melanoma received intismeran autogene 1 mg IM Q3W for up to 9 doses plus pembrolizumab 200 mg IV Q3W for up to 18 cycles (n=107) vs pembrolizumab alone (n=50); at ~5 years of planned follow-up, the combination sustained improved RFS (HR 0.510, 95% CI 0.294–0.887) and DMFS (HR 0.411, 95% CI 0.200–0.843), with an OS trend (HR 0.471, 95% CI 0.165–1.345). Safety remained manageable with no new signals reported, and the translational data showed increased TCR clonality/novel clonotypes, which matters because adjuvant pembrolizumab alone is already active in resected stage III melanoma, improving RFS vs placebo in KEYNOTE-054 with HR 0.57.