RAHWAY, N.J. — Merck and Moderna announced detailed positive recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) results from the Phase 3 INTerpath-001 trial on October 22, 2026. The data showed that intismeran in combination with KEYTRUDA reduced the risk of recurrence or death by 42% compared to KEYTRUDA alone.

At the primary pre-specified analysis after a median follow-up of 24.6 months, the combination therapy demonstrated a hazard ratio of 0.58 (95% CI, 0.45–0.75; two-sided p<0.001) versus KEYTRUDA alone. Intismeran plus KEYTRUDA also reduced the risk of distant metastasis or death by 38% (HR=0.62 [95% CI, 0.45–0.85]; two-sided p=0.002).

In the intent-to-treat population, the two-year RFS rate was 82.2% (95% CI, 79.3%–84.8%) for intismeran plus KEYTRUDA compared to 70.0% (95% CI, 65.0%–74.5%) for KEYTRUDA alone. The two-year DMFS rate was 88.5% (95% CI, 86.0%–90.6%) for the combination group versus 80.2% (95% CI, 75.6%–84.0%) for KEYTRUDA alone.

"INTerpath-001 is the first Phase 3 study to demonstrate a clinically meaningful improvement in RFS and DMFS over standard-of-care KEYTRUDA in patients with resected melanoma," said Dr. Dean Y. Li, president of Merck Research Laboratories.

The INTerpath-001 trial evaluated intismeran autogene, an investigational mRNA-based individualized neoantigen therapy jointly developed by Merck and Moderna, in combination with KEYTRUDA as adjuvant treatment for patients with completely resected stage IIB-IV melanoma. The randomized, double-blind, placebo- and active-comparator-controlled global Phase 3 trial enrolled 1,137 patients who were randomized 2:1 to receive intismeran and KEYTRUDA compared to placebo plus KEYTRUDA.

Patients received intismeran (1 mg every three weeks for up to nine doses) and KEYTRUDA (400 mg every six weeks up to nine cycles) compared to placebo plus KEYTRUDA for approximately one year. In a pre-specified sensitivity analysis after six months, the combination reduced the risk of recurrence or death by 58% (piecewise HR=0.42 [95% CI, 0.30–0.58]) and 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 population, 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. Overall survival data are not yet mature, but a favorable trend in overall survival with intismeran plus KEYTRUDA has been observed.

Treatment-related adverse events occurred in 95.8% (723 of 755 patients) receiving intismeran plus KEYTRUDA and 90.0% (342 of 380 patients) receiving KEYTRUDA alone. Grade 3–5 treatment-related adverse events occurred in 14.2% (n=107) of patients receiving the combination versus 13.4% (n=51) of patients receiving KEYTRUDA alone, with the most common adverse events in the intismeran plus KEYTRUDA arm being pyrexia (52.2%), injection site pain (51.0%) and fatigue (38.5%).

The safety profile of intismeran plus KEYTRUDA was generally consistent with previously reported studies of the combination, and no new safety signals were observed. "The transformative INTerpath-001 results have the potential to make a foundational shift in how we treat patients with earlier-stage melanoma in the adjuvant setting," said Professor Georgina Long, the study’s principal investigator.

"The INTerpath-001 results mark a defining moment for that vision and show what’s possible when we rethink how medicines are made," said Stéphane Bancel, Chief Executive Officer of Moderna. Merck and Moderna are engaging with regulatory authorities based on these data.

The results will be presented during Presidential Symposium I at the European Society for Medical Oncology (ESMO) Congress 2026 as Presentation #LBA1 and were selected for an official ESMO Press Briefing. The results have been accepted for publication in The New England Journal of Medicine.

Why It Matters

More than 338,000 new cases of melanoma were diagnosed worldwide in 2024. It is estimated there will be about 112,000 new cases of melanoma diagnosed and over 8,500 deaths resulting from the disease in the U.S. in 2026.

The INTerpath program currently consists of nine total Phase 2 and Phase 3 clinical trials across multiple tumor types and stages of disease, including three ongoing Phase 3 trials in non-small cell lung cancer.