Moderna and Merck report five‑year Phase 2b KEYNOTE‑942 results showing intismeran autogene (mRNA‑4157/V940) plus KEYTRUDA® delivers durable recurrence‑free survival benefit in resected stage III/IV melanoma, with favorable safety and translational immune insights.
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
Moderna and Merck presented long-term results from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study (NCT03897881) at the 2026 ASCO Annual Meeting, with simultaneous publication in the Journal of Clinical Oncology. The trial evaluated intismeran autogene (mRNA-4157/V940), an individualized mRNA neoantigen therapy, in combination with KEYTRUDA® (pembrolizumab) in patients with completely resected stage III/IV melanoma. A total of 157 patients were randomized 2:1 to receive the vaccine plus pembrolizumab or pembrolizumab alone.
Long-Term Outcomes
After a median follow-up of 60.3 months, the combination reduced the risk of recurrence or death by 49% compared with KEYTRUDA alone, meeting the primary endpoint of recurrence-free survival (RFS). The regimen also reduced the risk of distant metastasis or death by 59%, demonstrating durable benefit across key efficacy measures. Exploratory overall survival analysis showed a favorable trend (HR 0.471; 95% CI 0.165–1.345), although the limited number of events prevents definitive conclusions. Together, the findings indicate sustained improvements in both recurrence-free and distant metastasis-free survival at five years.
Mechanistic Insights
Intismeran autogene is a personalized mRNA-based cancer vaccine encoding up to 34 patient-specific neoantigens derived from the unique mutational profile of each tumor. Translational analyses demonstrated expansion of novel T-cell clonotypes in patients receiving the vaccine plus pembrolizumab, with higher levels of these responses associated with recurrence-free status. Immune responses were linked directly to vaccine-encoded neoantigens, supporting the proposed mechanism connecting vaccine-induced T-cell responses with clinical benefit.
Safety Profile
The combination maintained a favorable safety profile consistent with previous analyses. The most common treatment-related adverse events were fatigue, injection-site pain, and chills, with most events reported as Grade 1 or 2. Grade 3 fatigue was the most frequently reported severe adverse event, and no Grade 4 or 5 vaccine-related toxicities were observed. The addition of intismeran autogene did not increase immune-related adverse events compared with KEYTRUDA alone.
Regulatory and Development Outlook
The five-year findings provide important support for the ongoing Phase 3 INTerpath-001 melanoma study (NCT05933577), which is fully enrolled. Moderna and Merck continue to advance a broad late-stage development program evaluating intismeran autogene across multiple tumor types, including non-small cell lung cancer, bladder cancer, and renal cell carcinoma.
The companies recently initiated a Phase 3 study evaluating the therapy as both monotherapy and in combination with KEYTRUDA in patients with high-risk Stage I NSCLC, further expanding the personalized mRNA cancer vaccine platform.
If replicated in Phase 3 studies, these findings could support future regulatory filings and establish individualized neoantigen vaccines as a new adjuvant treatment approach in melanoma.
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About the Writer
Dr.Preethi Putti, PharmD (LinkedIn) is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.