On October 22, 2026, Moderna and Merck reported top-line Phase 3 results for intismeran, their personalized mRNA treatment for high-risk melanoma after surgery. In the INTerpath-001 trial, the companies reported a 42% lower relative risk of recurrence or death and a 38% lower relative risk of distant metastasis or death when intismeran was added to pembrolizumab, compared with pembrolizumab plus placebo.
NeoTeo previously covered the INTerpath-001 milestone announcement. The October results add numerical estimates for the trial’s recurrence and metastasis endpoints.
Who took part, and what did the trial compare?
INTerpath-001 enrolled 1,137 people with high-risk cutaneous melanoma that had been completely removed surgically. Participants had stage IIB, IIC, III, or IV disease and had not received prior systemic therapy. Researchers randomized them 2:1 to intismeran plus pembrolizumab or pembrolizumab plus placebo.
Intismeran, also known as V940 or mRNA-4157, is designed using mutations identified in an individual patient’s tumor. Its synthetic messenger RNA encodes up to 34 neoantigens, markers selected to help the immune system recognize tumor cells. In the trial, the intismeran dose was 1 mg every three weeks for up to nine doses. Pembrolizumab was given at 400 mg every six weeks for up to nine cycles in both groups.
How should the reported percentages be read?
Recurrence-free survival (RFS) measures time without disease recurrence or death. Distant metastasis-free survival (DMFS) measures time without melanoma spreading to distant sites or death. At about two years, the reported RFS rate was 82% with intismeran plus pembrolizumab and 70% with pembrolizumab plus placebo. The reported DMFS rates were 88.5% and 80%, respectively.
| Trial endpoint | Intismeran plus pembrolizumab | Pembrolizumab plus placebo | Reported relative risk reduction |
| RFS, about two years | 82% | 70% | 42% for recurrence or death |
| DMFS | 88.5% | 80% | 38% for distant metastasis or death |
The 42% and 38% figures are relative risk reductions, not percentage-point increases in the rates. The reported RFS rates differ by 12 percentage points; the DMFS rates differ by 8.5 percentage points. These measures describe different ways of expressing the trial results.
Overall survival (OS), which measures time until death from any cause, remained under evaluation. The reported RFS and DMFS results therefore do not establish that participants lived longer overall. The melanoma findings also do not establish that intismeran works in other cancers; Merck has described studies across other tumor types and stages as part of the development program.
What did MSK report about side effects and eligibility?
Memorial Sloan Kettering Cancer Center (MSK) reported that adverse events occurred in nearly 96% of the intismeran-plus-pembrolizumab group and 90% of the pembrolizumab-plus-placebo group. MSK said most were effects expected with pembrolizumab, and that intismeran did not increase pembrolizumab-related side effects. Fever, injection-site pain, and fatigue were among the common effects associated with the vaccine.
MSK described a potential future use for newly diagnosed patients with stage 2B or higher melanoma whose tumors can be completely removed surgically. Tissue from surgery is needed to make the individualized treatment. MSK reported on October 23, 2026, that intismeran had not been approved by the U.S. Food and Drug Administration (FDA).
