Moderna and Merck's Melanoma mRNA Therapy Keeps 49% Recurrence Cut at Five Years in Phase 2b
Intismeran autogene plus Keytruda continued to lower the risk of recurrence or death versus Keytruda alone in the 157-patient KEYNOTE-942 trial, the companies reported, as a Phase 3 melanoma trial is fully enrolled.
These results come from a Phase 2 trial, which tests whether a treatment works and refines the dose.
Key points
- Moderna and Merck reported that intismeran autogene plus Keytruda reduced the risk of recurrence or death by 49% versus Keytruda alone at a median five-year follow-up in the Phase 2b KEYNOTE-942 trial (HR 0.510).
- The trial enrolled 157 patients with high-risk stage III/IV melanoma after complete surgical removal; the companies said safety remained consistent with earlier reports.
- The Phase 3 INTerpath-001 trial in adjuvant melanoma is fully enrolled, and further KEYNOTE-942 data will be presented at a medical meeting, the companies said.
Moderna and Merck said on January 20 that their individualized mRNA cancer treatment intismeran autogene, given with Merck's Keytruda (pembrolizumab) after surgery, reduced the risk of melanoma recurrence or death by 49% compared with Keytruda alone at a median five years of follow-up in the Phase 2b KEYNOTE-942 trial, according to the companies' announcement, distributed by Newswire.com.
The result, a hazard ratio of 0.510 (95% CI, 0.294-0.887; one-sided nominal p=0.0075), is from a pre-planned analysis of the trial's primary endpoint, recurrence-free survival. The companies reported the topline figure and said they plan to present further data on the primary and secondary endpoints at an upcoming medical meeting. They described the safety profile of the combination as consistent with what was previously reported.
The trial
KEYNOTE-942 is an ongoing, randomized, open-label Phase 2b trial that enrolled 157 patients with high-risk stage III or IV melanoma whose tumors had been completely removed by surgery. Patients were assigned 2:1 to receive intismeran autogene every three weeks for nine doses plus Keytruda for about a year, or Keytruda alone for about a year. Secondary endpoints include distant metastasis-free survival and safety.
Intismeran autogene, also known as mRNA-4157 or V940, is designed from the DNA sequence of each patient's tumor. According to the companies, it consists of a synthetic mRNA coding for up to 34 neoantigens, intended to train the immune system to attack cells carrying those mutations.
The five-year analysis builds on the trial's primary analysis at about two years of follow-up and a later analysis at three years, the companies said. Targeted Oncology reported the same 49% figure on January 20.
Late-stage program
"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, Moderna's head of development, oncology and therapeutics, in the release.
The Phase 3 trial in adjuvant melanoma, INTerpath-001, is fully enrolled, according to the companies. Two Phase 3 studies in non-small cell lung cancer are enrolling, and Phase 2 studies are under way or enrolling in kidney cancer, bladder cancer, first-line metastatic melanoma and squamous lung cancer, for a total of eight Phase 2 and Phase 3 trials across tumor types.
"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 tumor types where significant unmet needs remain," said Marjorie Green, head of oncology global clinical development at Merck Research Laboratories.
Sources
- Moderna & Merck Announce 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA (pembrolizumab) Demonstrated Sustained Improvement in the Primary Endpoint of Recurrence-Free Survival, Moderna and Merck via Newswire.com, January 20, 2026
- RFS Benefit Sustained at 5 Years for Intismeran Autogene in Melanoma, Targeted Oncology, January 20, 2026