Merck (NYSE:MRK), known as MSD outside of the United States and Canada, and Moderna, Inc. (NASDAQ:MRNA) today announced positive topline results from the Phase 3 INTerpath-001 trial evaluating adjuvant treatment with intismeran autogene (intismeran; V940 or mRNA-4157), a novel investigational mRNA-based individualized neoantigen therapy (INT) being jointly developed by Merck and Moderna, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with completely resected stage IIB-IV melanoma. The trial met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS). This represents the first positive Phase 3 readout for an individualized neoantigen therapy (INT) and for an mRNA-based cancer therapy, as well as the first Phase 3 study to demonstrate a clinically meaningful improvement over KEYTRUDA alone, a standard-of-care immunotherapy, in the adjuvant setting for patients with resected melanoma.

At a pre-specified interim analysis, intismeran in combination with KEYTRUDA as adjuvant therapy demonstrated statistically significant and clinically meaningful improvements in RFS and DMFS compared to KEYTRUDA alone for patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not undergone prior treatment with systemic therapy. In accordance with the trial protocol, the study will continue in order to evaluate other key secondary endpoints, including overall survival (OS).

The safety profiles of intismeran and KEYTRUDA in this trial were consistent with those observed in previously reported studies for the combination, with no new safety signals observed.

These data will be presented at an upcoming international medical meeting and shared with regulatory authorities.

“Today’s results represent a landmark moment for adjuvant melanoma treatment. This is the first Phase 3 study to show that intismeran, a treatment designed based on the unique mutational ‘fingerprint’ of a patient’s own tumor, given in combination with pembrolizumab can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to KEYTRUDA alone,” said Professor Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia, Chair of Melanoma Medical Oncology and Translational Research at the University of Sydney. “Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”

“By intervening earlier in the course of disease, when many cancers are considered most treatable, the goal of adjuvant therapy given after surgery is to increase the possibility of cure for more patients,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “These first Phase 3 findings for intismeran in combination with KEYTRUDA as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment. We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated. Together with Moderna, we look forward to presenting data from INTerpath-001 at an international medical meeting and sharing with regulatory authorities.”

“These Phase 3 findings represent a pivotal moment for the field of cancer research. For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality,” said Stéphane Bancel, CEO of Moderna. “Together with Merck, we have started to demonstrate the transformative potential of this technology to address critical unmet needs in the adjuvant melanoma setting. We are deeply grateful to the patients, investigators and study teams whose contributions make this progress possible.”

Merck and Moderna are advancing the robust INTerpath clinical development program evaluating the safety and efficacy of intismeran in combination with KEYTRUDA and other anti-cancer therapies, and as a monotherapy. The INTerpath program currently consists of nine total Phase 2 and Phase 3 clinical trials across multiple tumor types and stages of disease, including melanoma, non-small cell lung cancer (NSCLC), bladder cancer and renal cell carcinoma. Additional clinical studies include the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma and a Phase 1 study exploring adjuvant pancreatic ductal adenocarcinoma, perioperative gastric carcinoma and perioperative NSCLC.

Today’s Phase 3 readout builds on previously reported Phase 2b results for intismeran in combination with KEYTRUDA from the KEYNOTE-942/mRNA-4157-P201 trial, including the five-year follow-up data presented at the 2026 ASCO Annual Meeting, in which the combination demonstrated a 49% reduction in the risk of recurrence or death (HR=0.51; [95% CI, 0.294-0.887]) and a 59% reduction in the risk of distant metastasis or death (HR=0.411; [95% CI, 0.200-0.843]) compared to KEYTRUDA alone.