Research Summary

Intismeran Autogene mRNA Therapy Plus Pembrolizumab Meets Phase 3 Endpoints in Resected Melanoma

Edited by:
Anthony Calabro, MA

Key Highlights

  • Intismeran autogene, an investigational mRNA-based individualized neoantigen therapy, was evaluated with pembrolizumab as adjuvant therapy for completely resected stage IIB-IV cutaneous melanoma.
  • The randomized, double-blind, placebo- and active-comparator-controlled phase 3 INTerpath-001 trial enrolled 1,137 patients.
  • At a prespecified interim analysis, the combination significantly improved recurrence-free survival and distant metastasis-free survival compared with pembrolizumab alone; numerical phase 3 efficacy results were not reported.

On August 19, 2026, Merck & Co, Inc, and Moderna, Inc, announced positive topline results from the phase 3 INTerpath-001 trial evaluating intismeran autogene (V940 or mRNA-4157), jointly developed by both companies, plus pembrolizumab (Keytruda, Merck & Co, Inc) as adjuvant therapy for patients with completely resected stage IIB-IV melanoma.

Intismeran is an investigational mRNA-based individualized neoantigen therapy designed using a patient’s tumor sample to identify its unique mutational signature. Each individualized therapy consists of synthetic mRNA coding for up to 34 neoantigens.

INTerpath-001 is a randomized, double-blind, placebo- and active-comparator-controlled global phase 3 trial that enrolled 1,137 patients with high-risk, stage IIB-IV resected cutaneous melanoma. Following complete surgical resection, patients were randomly assigned 2:1 to intismeran plus pembrolizumab or pembrolizumab alone.

At a prespecified interim analysis, the combination demonstrated statistically significant improvements in recurrence-free survival (RFS), the primary endpoint, and distant metastasis-free survival (DMFS), a key secondary endpoint, compared with pembrolizumab alone. The trial will continue to evaluate other key secondary endpoints, including overall survival, safety, tolerability, and quality of life. The safety profiles of intismeran and pembrolizumab were consistent with those observed in previously reported studies of the combination, with no new safety signals identified.

Patients in the combination group received intismeran 1 mg every 3 weeks for up to 9 doses and pembrolizumab 400 mg every 6 weeks for up to 9 cycles. Treatment continued for approximately 1 year until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever occurred first. Both companies said the data will be presented at an upcoming international medical meeting and shared with regulatory authorities.

Reference
Merck, Moderna. 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. Published August 19, 2026. Accessed August 19, 2026. https://www.merck.com/news/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-patient