Merck and Moderna Announced mRNA-based Therapy Reduced Recurrence and Death in Melanoma

Adding the investigational individualized neoantigen therapy intismeran autogene to pembrolizumab reduced the risk of recurrence or death compared with pembrolizumab alone in patients with completely resected stage IIB-IV melanoma, Merck and Moderna announced ahead of the results’ presentation at the European Society for Medical Oncology Congress 2026 Presidential Symposium.

Intismeran autogene (Merck and Moderna), also known as V940 or mRNA-4157, is an mRNA-based therapy designed from a patient’s tumor sample to identify the tumor’s unique mutational signature and generate an antitumor immune response. It was given with pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy.

The randomized, double-blind phase 3 INTerpath-001 trial enrolled 1,137 patients with resected stage IIB-IV cutaneous melanoma. They were randomly assigned 2:1 to intismeran 1mg every 3 weeks for up to 9 doses plus pembrolizumab 400mg every 6 weeks for approximately 1 year, or to placebo plus pembrolizumab. After a median follow-up of 24.6 months, the combination reduced the risk of recurrence or death, the primary recurrence-free survival (RFS) endpoint, by 42% (hazard ratio, 0.58; 95% CI, 0.45-0.75). Two-year RFS was 82.2% with the combination and 70.0% with pembrolizumab alone.

The risk of distant metastasis or death, a key secondary endpoint, was 38% lower with the combination. No clear difference between arms was seen during the first 6 months; after 6 months, a prespecified sensitivity analysis showed a 58% lower risk of recurrence or death. The companies said results were generally consistent across prespecified subgroups. Grade 3-5 treatment-related adverse events occurred in 14.2% of the combination arm and 13.4% of the pembrolizumab-alone arm. Pyrexia, injection site pain, and fatigue were the most common adverse events with the combination, and the companies reported no new safety signals.

Overall survival data are not yet mature, and the study is ongoing. The companies said the results have been accepted for publication in The New England Journal of Medicine and that they are engaging with regulatory authorities. Pembrolizumab’s US adjuvant melanoma indication covers completely resected stage IIB, IIC, or III disease in patients 12 years and older.

Source: Merck. Merck and Moderna will present results from landmark phase 3 INTerpath-001 trial for intismeran autogene plus Keytruda (pembrolizumab) at ESMO 2026 Presidential Symposium. News release. Merck; October 22, 2026. Accessed October 23, 2026.