Merck And Moderna Report Phase 3 Melanoma Trial Results For Personalized mRNA Cancer Therapy; Intismeran Plus KEYTRUDA Cuts Melanoma Recurrence Or Death Risk By 42%

Intismeran plus KEYTRUDA significantly reduced the risk of recurrence or death by 42% (HR=0.58 [95% CI, 0.45–0.75]; two-sided p<0.001) compared to KEYTRUDA alone for patients with completely resected stage IIB-IV melanoma

Benefit was greater after six months, following the intismeran immunization regimen, as intismeran plus KEYTRUDA reduced the risk of recurrence or death by 58% (piecewise HR=0.42 [95% CI, 0.30–0.58]) compared to KEYTRUDA alone in a pre-specified sensitivity analysis

Merck (NYSE:MRK), known as MSD outside of the United States and Canada, and Moderna, Inc. (NASDAQ:MRNA) today announced detailed positive recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) results from the Phase 3 INTerpath-001 trial evaluating intismeran autogene (intismeran; V940 or mRNA-4157), a novel investigational mRNA-based individualized neoantigen therapy (INT) being jointly developed by Merck and Moderna, in combination with KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 therapy, as adjuvant treatment for patients with completely resected stage IIB-IV melanoma. These late-breaking results will be presented for the first time during Presidential Symposium I at the European Society for Medical Oncology (ESMO) Congress 2026 (Presentation #LBA1), were selected for an official ESMO Press Briefing and have been accepted for publication in The New England Journal of Medicine.

At the primary pre-specified analysis (intention-to-treat), after a median follow-up of 24.6 months, intismeran in combination with KEYTRUDA significantly reduced the risk of recurrence or death by 42% (HR=0.58 [95% CI, 0.45–0.75]; two-sided p<0.001). Intismeran plus KEYTRUDA also significantly reduced the risk of distant metastasis or death by 38% (HR=0.62 [95% CI, 0.45–0.85]; two-sided p=0.002) compared to KEYTRUDA alone. The improvements observed in RFS and DMFS were generally consistent across pre-specified patient subgroups. Overall survival (OS) data are not yet mature, but a favorable trend in OS with intismeran plus KEYTRUDA has been observed. The study remains ongoing to further evaluate OS and other key endpoints. The safety profile of intismeran plus KEYTRUDA was generally consistent with previously reported studies of the combination, and no new safety signals were observed. Based on these data, we are engaging with regulatory authorities.

The efficacy of the intismeran immunization plus KEYTRUDA in the first six months was comparable with KEYTRUDA alone for risk of recurrence or death (HR=0.99 [95% CI, 0.66–1.49]) and risk of distant metastasis or death (HR=1.01 [95% CI, 0.58–1.79]). At six months, following the intismeran immunization regimen, a pre-specified sensitivity analysis of the primary endpoint showed the addition of intismeran plus KEYTRUDA reduced the risk of recurrence or death by 58% (HR=0.42 [95% CI, 0.30–0.58]) and reduced the risk of distant metastasis or death by half (HR=0.50 [95% CI, 0.34–0.73]) compared to KEYTRUDA alone.

In a pre-specified sensitivity analysis of the modified intent-to-treat (mITT) population, which excluded participants who did not receive at least one dose of intismeran or placebo as planned, intismeran plus KEYTRUDA reduced the risk of recurrence or death by 49% (HR=0.51 [95% CI, 0.39–0.67]) and the risk of distant metastasis or death by 45% (HR=0.55 [95% CI, 0.40–0.77]) compared to KEYTRUDA alone.