mRNA-4157 maintains 5-year RFS in melanoma

Moderna and Merck said on January 20 that five-year follow-up from the phase 2b KEYNOTE-942 study showed their personalized mRNA cancer vaccine, intismeran autogene, maintained a recurrence-free survival benefit when added to pembrolizumab in patients with high-risk stage III or IV melanoma after complete resection. The update kept alive one of the most closely watched tests of whether mRNA can work as a personalized cancer treatment rather than only as an infectious-disease platform. The regimen is also known as mRNA-4157 or V940, and pembrolizumab is sold as Keytruda. The companies said the data came from a preplanned analysis. ### How strong was the five-year result? Merck said the combination reduced the risk of recurrence or death by 49% compared with pembrolizumab alone at a median five-year follow-up, with a hazard ratio of 0.510 and a 95% confidence interval of 0.294 to 0.887. CancerNetwork, citing the company release, described the effect as sustained and clinically meaningful in patients with resected high-risk melanoma. AACR’s *Cancer Discovery* also reported that the five-year data showed the vaccine continued to lower the risk of melanoma recurrence or death by about 49% when combined with pembrolizumab. (merck.com) ### What exactly is mRNA-4157? Intismeran autogene is an investigational individualized neoantigen therapy designed from a patient’s tumor mutations. Moderna says the approach uses tumor DNA and RNA sequencing to identify neoantigens and then makes a custom mRNA product intended to train T cells to recognize those tumor-specific targets. In KEYNOTE-942, that personalized vaccine was tested as adjuvant treatment with pembrolizumab after complete surgical resection. (merck.com) ### Who was studied in KEYNOTE-942? ClinicalTrials.gov lists KEYNOTE-942, also called mRNA-4157-P201, as a study in patients with high-risk melanoma after complete resection. Merck said the five-year analysis covered patients with stage III or IV melanoma. The trial compared intismeran autogene plus pembrolizumab against pembrolizumab alone in the adjuvant setting, where treatment is given after surgery to try to prevent the cancer from returning. (modernatx.com) ### Why does the FDA designation matter here? The U.S. Food and Drug Administration’s breakthrough therapy program is meant to speed development and review for drugs that treat serious conditions when preliminary clinical evidence suggests substantial improvement over available therapy on a clinically significant endpoint, the agency says. Moderna says mRNA-4157/V940 in combination with pembrolizumab received breakthrough therapy designation for adjuvant treatment of patients with high-risk melanoma following complete resection based on phase 2b data. (clinicaltrials.gov) That status does not equal approval, but it can give the companies closer FDA interaction as they move through later-stage development. ### Is this enough to change treatment now? AACR’s *Cancer Discovery* said the durability of the five-year signal strengthens confidence in the personalized vaccine approach, but added that a larger phase 3 trial will provide the decisive findings. Merck and Moderna have already started that next step: Merck said in 2023 that the V940-001 phase 3 study in resected high-risk stage IIB to IV melanoma had begun global recruitment, with first patients enrolling in Australia. (fda.gov) ### What comes next in the program? Merck said on January 20 that further data from follow-up analyses of KEYNOTE-942’s primary and secondary endpoints would be presented at a future medical conference. Merck also said this month that ASCO 2026 would include long-term data for intismeran autogene, while the broader development program now spans phase 2 and phase 3 trials in melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma. (merck.com) (aacrjournals.org)