Abstract:
Merck and Moderna announced the detailed results of a key phase III clinical trial: the combination of personalized mRNA therapy intismeran autogene (V940, formerly codenamed mRNA-4157) and the immunotherapy drug pembrolizumab can reduce the risk of postoperative recurrence or death in patients with high-risk melanoma. The research results were announced at the 2026 European Society of Medical Oncology Annual Meeting and have been accepted for publication by the New England Journal of Medicine.
The global Phase 3 trial, called INTerpath-001, enrolled 1,137 patients with cutaneous melanoma whose tumors had been surgically removed and whose disease was staged IIB to IV. Patients were divided into groups in a ratio of about 2 to 1, with one group receiving a combination of the personalized vaccine and pembrolizumab, and the other group receiving a placebo injection plus pembrolizumab. The median follow-up time was 24.6 months.
The results showed that compared with pembrolizumab alone, combined treatment reduced the risk of recurrence or death by 42%; the two-year recurrence-free survival rate was 82.2%, compared with 70% in the control group. The risk of distant metastasis or death was reduced by 38%, and the two-year distant metastasis-free survival rate was 88.5%, compared with 80.2% in the control group. The “risk reduction” here refers to the relative risk change calculated by clinical trials, and does not mean that the probability of recurrence of individual patients will decrease by the same proportion.
Research has not proven that this regimen extends overall survival. Overall survival data are still immature, and the research team continues to follow patients; only favorable trends are observed so far. Therefore, the main benefit shown in the trial was an improvement in indicators related to recurrence and distant metastasis, and it cannot be concluded that the vaccine has reduced mortality.
This type of vaccine is not a vaccination for healthy people, but an adjuvant treatment after surgery. The purpose is to allow the immune system to recognize and attack any remaining cancer cells. Researchers will analyze the patient's resected tumor and normal DNA, screen for tumor-specific mutations and neoantigens, and then create a synthetic mRNA vaccine containing corresponding instructions; each dose is designed to encode up to 34 neoantigens. Vaccines prompt the body to present these targets and activate tumor-specific T cells, and pembrolizumab helps immune cells maintain anti-tumor responses by blocking the PD-1 immune checkpoint.
In the trial, 95.8% of patients in the vaccine and pembrolizumab groups experienced treatment-related adverse events, compared with 90% in the control group; the proportions of adverse events with severity levels of grade 3 to 5 were 14.2% and 13.4% respectively. The more common reactions in the combination treatment group included fever, injection site pain and fatigue, and the study found no new safety signals.
This result provides important Phase III evidence to date for personalized cancer vaccines, but the treatment still needs to be designed and produced individually for each patient's tumor, and follow-up is needed to confirm long-term benefits. The therapy has not yet been approved by the U.S. Food and Drug Administration; Merck and Moderna said they are communicating with regulatory agencies and there is no definite time for launch or approval.
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