Moderna and Merck Report Five-Year Melanoma Data for V940 Plus KEYTRUDA, Personalised mRNA Therapy Shows Durable Benefit in High-Risk Melanoma

Moderna and Merck announced updated median five-year follow-up results from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study evaluating intismeran autogene (mRNA-4157/V940), an individualized mRNA-based neoantigen therapy, in combination with KEYTRUDA® for patients with high-risk stage III/IV melanoma following complete surgical resection. The data demonstrate that the combination continues to deliver durable and clinically meaningful benefit compared with KEYTRUDA alone.

In this pre-planned long-term analysis, adjuvant treatment with intismeran autogene plus KEYTRUDA reduced the risk of recurrence or death by 49% as measured by the study’s primary endpoint, recurrence-free survival. The hazard ratio was 0.510, with a 95% confidence interval of 0.294 to 0.887 and a one-sided nominal p-value of 0.0075, confirming sustained efficacy over extended follow-up.

“Now with five years of follow-up data, today’s results highlight the potential of a prolonged benefit of the intismeran autogene and KEYTRUDA combination in patients with resected high-risk melanoma,” said Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Oncology and Therapeutics. “We continue to invest in our platform in oncology because of encouraging outcomes like these, which illustrate mRNA’s potential in cancer care. We look forward to several additional milestones to come, including the results of our Phase 3 study in adjuvant melanoma in collaboration with Merck, and continued progress across the eight Phase 2 and Phase 3 studies in multiple tumor types and patient populations.” 

These findings build on previously reported analyses at approximately 2 and 3 years of follow-up, reinforcing the long-term potential of personalised mRNA-based immunotherapy in melanoma. The safety profile of the combination therapy remained consistent with earlier reports, with no new safety signals observed over the five-year period.

“For many patients with stage III/IV melanoma, there is a significant risk of recurrence following surgery. As such, demonstrating the longer-term potential of intismeran autogene and KEYTRUDA to reduce the risk of recurrence for certain patients with melanoma is a meaningful milestone,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “These five-year follow up data are encouraging, and we look forward to late-stage data from the INTerpath clinical development program with Moderna, across a range of tumour types where significant unmet needs remain.” 

Beyond melanoma, Moderna and Merck continue to advance a broad clinical development program for intismeran autogene. The Phase 3 INTerpath-001 trial in adjuvant melanoma is fully enrolled, while multiple Phase 3 and Phase 2 studies across non-small cell lung cancer, renal cell carcinoma, bladder cancer, and metastatic melanoma and squamous NSCLC are either fully enrolled or actively recruiting patients.