Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study

Cancer research · Melanoma

Intismeran plus pembrolizumab prolongs recurrence‑free survival and distant metastasis‑free survival compared with pembrolizumab alone in high‑risk resected melanoma.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA‑based individualized neoantigen therapy. We report 5‑year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE‑942 study. Eligible patients with resected stage IIIB‑IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab alone. The primary endpoint was recurrence‑free survival (RFS); secondary endpoints included distant metastasis‑free survival (DMFS) and safety. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), median planned follow‑up at data cutoff (December 15, 2025) was 60.3 months. Intismeran plus pembrolizumab continued to prolong RFS (HR = 0.510, 95% CI = 0.294‑0.887) and DMFS (HR = 0.411, 95% CI = 0.200‑0.843), with a favorable trend in overall survival (HR = 0.471, 95% CI = 0.165‑1.345) versus pembrolizumab, and a manageable safety profile.

This trial demonstrates that adding personalized mRNA‑based neoantigen therapy can further reduce recurrence and improve long‑term outcomes in high‑risk melanoma patients, addressing an unmet need for durable adjuvant treatments.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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