mRNA cancer vaccine cut melanoma recurrence in phase 3 data

Clinical takeaway: Investigational intismeran added to pembrolizumab cut recurrence, but overall survival is still being followed. The sponsors say they are engaging regulators but have announced no filing date. 

Many patients with resected high-risk melanoma relapse despite adjuvant therapy. Pembrolizumab is approved in the US as adjuvant therapy after resection of stage IIB, IIC and III disease. Adding a second immune-directed therapy is one way to lower relapse further. 

This phase 3 trial extends phase 2b evidence for intismeran autogene, an mRNA-based therapy built from each tumor, by testing it with pembrolizumab against pembrolizumab alone. 

Adding intismeran to pembrolizumab raised two-year recurrence-free survival to 82.2%, versus 70.0% on pembrolizumab alone. That lowered the risk of recurrence or death by 42%. Distant metastasis or death also fell. The benefit was similar in stage IIB–IIIB and IIIC–IV disease. Overall survival data are not yet mature. Median recurrence-free survival was not reached in either arm. 

Fever and injection site pain each affected about half of patients on intismeran, versus fewer than one in 10 on pembrolizumab alone. Grade 3 or higher adverse events occurred in 23.6% of patients on intismeran versus 20.3% on pembrolizumab alone. Adverse events led 6.5% on intismeran to stop both drugs, versus 5.3% on pembrolizumab alone. 

The double-blind INTerpath-001 trial randomized 1,137 adults with completely resected stage IIB to IV cutaneous melanoma, 2:1 to intismeran plus pembrolizumab or placebo plus pembrolizumab. Patients needed a tumor sample suitable for sequencing. The primary endpoint was recurrence-free survival. Median follow-up was 24.6 months. 

Full results will be presented at ESMO on Oct 24 and have been accepted for publication in The New England Journal of Medicine. Three phase 3 trials in non-small cell lung cancer are also ongoing. 

“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 Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia, Chair of Melanoma Medical Oncology and Translational Research at the University of Sydney. 

“For decades, cancer treatment has largely been defined by where a tumor originates in the body. The INTerpath-001 findings support a fundamentally new and individualized approach to treating resected melanoma in the adjuvant setting, one that tailors treatment to the unique mutational signature of a patient’s tumor to enhance an anti-tumor immune response,” she concluded. “While these results are in patients with completely resected stage IIB-IV melanoma, they provide valuable insights and will help inform our understanding of intismeran as clinical research continues into other tumor types and across settings.” 

Source: Merck and Moderna (2026 Oct 22) Merck and Moderna Will Present Results From Landmark Phase 3 INTerpath-001 Trial for Intismeran Autogene Plus KEYTRUDA® (pembrolizumab) at ESMO 2026 Presidential Symposium; Long GV, et al. (2026 Oct 24) ESMO Congress 2026 Abstract LBA1