The Intismeran KEYTRUDA melanoma trial has delivered its first positive Phase 3 results, Merck (NYSE: MRK) and Moderna, Inc. (NASDAQ: MRNA) announced on August 19, 2026. Topline data from the Phase 3 INTerpath-001 study show that intismeran autogene, an investigational mRNA-based individualized neoantigen therapy (INT), combined with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab), met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma.
The companies describe the readout as the first positive Phase 3 result for an individualized neoantigen therapy and for an mRNA-based cancer therapy overall. It is also the first Phase 3 study to show a clinically meaningful improvement over KEYTRUDA alone, the current standard-of-care immunotherapy, in the adjuvant setting for patients with resected melanoma.
At a pre-specified interim analysis, the Intismeran KEYTRUDA Melanoma Trial produced statistically significant and clinically meaningful improvements in both RFS and DMFS compared with KEYTRUDA alone. The population studied included patients with completely resected stage IIB, IIC, III, or IV cutaneous melanoma who had not previously received systemic therapy. Per the trial protocol, INTerpath-001 will continue so that additional secondary endpoints, including overall survival (OS), can be evaluated.
The safety profile observed in the Intismeran KEYTRUDA Melanoma Trial was consistent with earlier studies of the combination, and no new safety signals emerged. Merck and Moderna said the data will be presented at an upcoming international medical meeting and shared with regulatory authorities as the companies weigh filing submissions for intismeran autogene in combination with KEYTRUDA.
How the Intismeran KEYTRUDA Melanoma Trial Was Designed
The Intismeran KEYTRUDA Melanoma Trial, formally designated INTerpath-001, is a randomized, double-blind, placebo- and active-comparator-controlled global Phase 3 trial registered as NCT05933577 on ClinicalTrials.gov. The study enrolled 1,137 patients with high-risk, stage IIB-IV resected cutaneous melanoma. Following complete surgical resection, patients were randomized 2:1 to receive intismeran (1 mg every three weeks, for up to nine doses) plus KEYTRUDA (400 mg every six weeks, for up to nine cycles) for approximately one year, or KEYTRUDA alone for a comparable duration, until disease recurrence, unacceptable toxicity, or a maximum treatment period of roughly 56 weeks.
The trial’s primary endpoint, RFS, is defined as the time from randomization to any disease recurrence, local, locoregional, regional, or distant, as assessed by the investigator, or death from any cause. Key secondary endpoints include DMFS, OS, safety, tolerability, and quality of life. Professor Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia, called the readout a landmark moment, noting that intismeran combined with pembrolizumab “has the potential to establish a new treatment paradigm in the adjuvant melanoma setting.”
Results from the Intismeran KEYTRUDA Melanoma Trial build directly on earlier data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial. Five-year follow-up data presented at the 2026 ASCO Annual Meeting showed the intismeran-KEYTRUDA combination reduced the risk of recurrence or death by 49% (HR=0.51; 95% CI, 0.294-0.887) and reduced the risk of distant metastasis or death by 59% (HR=0.411; 95% CI, 0.200-0.843), each compared with KEYTRUDA alone.
Inside the Intismeran KEYTRUDA Melanoma Trial: How Intismeran Autogene Works
Intismeran autogene, also known as intismeran, V940, or mRNA-4157, is a novel, potential first-in-class mRNA-based individualized neoantigen therapy jointly developed by Merck and Moderna. It is manufactured from a patient’s own tumor sample, identifying the unique mutational signature, or “fingerprint,” of that individual’s cancer. Each dose consists of a synthetic mRNA encoding up to 34 neoantigens tailored to the specific biology of the patient’s tumor. Once administered, the RNA-encoded neoantigen sequences are translated in the body and presented to the immune system, a step designed to generate targeted T-cell responses against cancer cells.
Dr. Dean Y. Li, president of Merck Research Laboratories, said the goal of adjuvant therapy is to intervene earlier in the disease course, at the point when cancer is generally most treatable, in order to increase the chance of cure for more patients. Stéphane Bancel, chief executive officer of Moderna, called the finding a pivotal moment for cancer research, noting that turning an individualized mRNA cancer treatment from an aspiration into reality required years of collaboration between the two companies.
Melanoma Burden and the INTerpath Program Beyond This Intismeran KEYTRUDA Melanoma Trial
Melanoma is one of the deadliest forms of skin cancer, driven by uncontrolled growth of pigment-producing cells, and diagnosis rates have climbed over the past several decades. Worldwide, more than 330,000 new melanoma cases were diagnosed in 2022. In the United States, an estimated 112,000 new melanoma cases and more than 8,500 melanoma deaths are projected for 2026. Even after successful resection, patients remain at risk of recurrence, most commonly within the first two years, and most recurrences are metastatic rather than localized — underscoring the need for treatments that can reduce that risk.
The Intismeran KEYTRUDA Melanoma Trial sits within Merck and Moderna’s broader INTerpath clinical development program, which now spans nine total Phase 2 and Phase 3 trials evaluating intismeran in combination with KEYTRUDA and other anti-cancer therapies, as well as as a monotherapy, across melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma. The program also includes 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.
What Comes Next for the Intismeran KEYTRUDA Melanoma Trial Program
KEYTRUDA already holds U.S. approval for adjuvant treatment of resected Stage IIB, IIC, or III melanoma, based on the KEYNOTE-054 and KEYNOTE-716 trials, in addition to its approval for unresectable or metastatic melanoma. Merck says it continues to explore novel KEYTRUDA combinations and investigational individualized neoantigen therapies as part of a decade-long melanoma research program aimed at improving long-term outcomes.
With the Intismeran KEYTRUDA Melanoma Trial continuing toward its OS readout, Merck and Moderna are positioning the combination as a potential new standard in adjuvant melanoma care. The companies said they plan to engage regulators on filing submissions and will present full data from the trial at an upcoming international medical meeting, where the magnitude of the RFS and DMFS benefit is expected to be disclosed alongside updated safety findings.
