INTerpath-001: Intismeran Plus Pembrolizumab Meets Dual Phase 3 Melanoma Endpoints

Merck and Moderna reported positive topline results from the phase 3 INTerpath-001 trial evaluating intismeran autogene (V940; mRNA-4157) plus pembrolizumab (Keytruda) as adjuvant therapy for completely resected stage IIB-IV cutaneous melanoma.

The individualized mRNA-based neoantigen therapy combination met the study’s primary endpoint of recurrence-free survival (RFS) and key secondary endpoint of distant metastasis-free survival (DMFS), according to the companies. Intismeran plus pembrolizumab produced statistically significant and clinically meaningful improvements in both endpoints compared with pembrolizumab alone.

Individualized mRNA Therapy Advances in Adjuvant Melanoma

INTerpath-001 included patients with completely resected stage IIB, IIC, III, or IV cutaneous melanoma who were not recieving prior systemic therapy. The companies did not disclose hazard ratios, absolute event rates, P values, or other phase 3 efficacy estimates in the topline announcement. According to a news release from Merck, the study will continue according to protocol to evaluate additional secondary endpoints, including overall survival. No new safety signals were reported, and the safety profiles were described as consistent with previously reported studies of the combination.

The phase 3 findings follow results from the phase 2b KEYNOTE-942/mRNA-4157-P201 trial. At 5-year follow-up, intismeran plus pembrolizumab was associated with a 49% reduction in the risk of recurrence or death (HR, 0.51; 95% CI, 0.294 to 0.887) and a 59% reduction in the risk of distant metastasis or death (HR, 0.411; 95% CI, 0.200 to 0.843) compared with pembrolizumab alone. 

“These Phase 3 findings represent a pivotal moment for the field of cancer research,” Moderna CEO Stéphane Bancel said in the news release. The manufacturers plan to present detailed INTerpath-001 data at an upcoming international medical meeting.

Source

Merck press release. August 19, 2026.