Individualized mRNA Therapy Plus Pembrolizumab Lowers Recurrence Risk in Resected Melanoma
By: Lisa Astor
Posted: Friday, November 6, 2026
Adding the mRNA-based individualized neoantigen therapy intismeran autogene to adjuvant pembrolizumab significantly prolonged recurrence-free survival and distant metastasis–free survival over pembrolizumab alone in patients with resected stage IIB to IV melanoma, according to results of the phase III INTerpath-001 trial presented at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA1).
Many patients with high-risk melanoma still experience relapse on adjuvant immunotherapy even after surgical resection. Intismeran autogene is built from each patient’s own tumor sequencing data and is designed to broaden antitumor T-cell responses by targeting neoantigens unique to that tumor, both expanding existing T-cell populations and prompting new ones.
The double-blind trial enrolled adults with surgically resected stage IIB or IIC, III, or IV cutaneous melanoma and available tumor samples for next-generation sequencing. In all, 1,137 patients were randomly assigned 2:1 to pembrolizumab at 400 mg intravenously every 6 weeks for nine cycles with either intismeran autogene at 1 mg (n = 757) or placebo (n = 380) given intramuscularly every 3 weeks for nine doses. Pembrolizumab began at randomization, and the individualized therapy or placebo started once it was available. Recurrence-free survival was the primary endpoint, with distant metastasis-free survival, overall survival, and safety as secondary endpoints.
At a median follow-up of 24.6 months, the 24-month recurrence-free survival rate was 82.2% (95% confidence interval [CI] = 79.3%–84.8%) with the combination vs 70.0% (95% CI = 65.0%–74.5%) with pembrolizumab alone (HR = 0.58, 95% CI = 0.45–0.75; two-sided P < .001). The 24-month distant metastasis–free survival rate was 88.5% (95% CI = 86.0%–90.6%) vs 80.2% (95% CI = 75.6%–84.0%), respectively (HR = 0.62, 95% CI = 0.45–0.85; two-sided P = .002). Benefit was consistent across subgroups, including stage IIB to IIIB and stage IIIC to IV disease.
Grade 3 or higher adverse events occurred in 23.6% of patients in the combination arm and in 20.3% of the control group, and 6.5% vs 5.3%, respectively, stopped both drugs at once due to an adverse event. Fever, injection site pain, and fatigue were the most common adverse events, each reported more often with the individualized therapy.
“These findings set a new benchmark for adjuvant melanoma and are a pivotal advance in personalized medicine and cancer treatment,” concluded presenting author Georgina V. Long, PhD, MBBS, FRACP, FAHMS, of Melanoma Institute Australia, Sydney, and colleagues.
Disclosure: The study was funded by Merck Sharp & Dohme LLC and Moderna, Inc.
