RAHWAY, N.J. & CAMBRIDGE, Mass. — Merck and Moderna said a Phase 3 trial of their individualized mRNA cancer therapy intismeran autogene in combination with KEYTRUDA met its primary and a key secondary endpoint in patients with completely resected stage IIB-IV melanoma.
The INTerpath-001 trial found that intismeran autogene, also known as V940 or mRNA-4157, plus KEYTRUDA, or pembrolizumab, produced statistically significant and clinically meaningful improvements in recurrence-free survival and distant metastasis-free survival compared with KEYTRUDA alone, the companies said.
The companies described the results as the first positive Phase 3 readout for an individualized neoantigen therapy and an mRNA-based cancer therapy. The study is continuing to evaluate additional secondary endpoints, including overall survival.
Intismeran is an investigational mRNA-based individualized neoantigen therapy designed specifically for each patient based on mutations identified in that patient’s tumor. The approach is intended to train the immune system to recognize and attack cancer cells.
The trial included patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not previously received systemic therapy.
The safety profiles of intismeran and KEYTRUDA were consistent with those seen in earlier studies of the combination, and no new safety signals were identified, according to Merck and Moderna.
“Today’s results represent a landmark moment for adjuvant melanoma treatment,” said Professor Georgina Long, the study’s principal investigator and Medical Director of Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research at the University of Sydney.
“This is the first Phase 3 study to show that intismeran, a treatment designed based on the unique mutational ‘fingerprint’ of a patient’s own tumor, given in combination with pembrolizumab can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to KEYTRUDA alone,” Long said.
Dr. Dean Y. Li, President of Merck Research Laboratories, said the findings reinforce the potential of a more personalized approach to cancer treatment.
“These first Phase 3 findings for intismeran in combination with KEYTRUDA as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment,” Li said. “We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated.”
Moderna CEO Stéphane Bancel called the results a pivotal development for mRNA-based cancer treatments.
“For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality,” Bancel said.
Merck and Moderna said they plan to present detailed results from INTerpath-001 at an upcoming international medical meeting and discuss potential regulatory submissions with health authorities.
INTerpath-001 is a randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial that enrolled 1,137 patients. Participants were randomized 2:1 after complete surgical resection to receive intismeran plus KEYTRUDA or KEYTRUDA alone.
Patients in the combination arm received 1 mg of intismeran every three weeks for up to nine doses and KEYTRUDA at 400 mg every six weeks for up to nine cycles, or about one year.
The companies are also evaluating intismeran through the broader INTerpath clinical development program, which includes nine Phase 2 and Phase 3 trials across cancers including melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma.
The Phase 3 findings build on previous Phase 2b results from the KEYNOTE-942/mRNA-4157-P201 study. Five-year follow-up data presented at the 2026 ASCO Annual Meeting showed the intismeran-KEYTRUDA combination reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 59% compared with KEYTRUDA alone.
