Multinational phase 2b trial of addition of intismeran autogene to pembrolizumab for high-risk resected melanoma: 5-year update of KEYNOTE-942

Intismeran autogene (intismeran) is an mRNA-based individualized neoantigen therapy. The multinational randomized phase 2b KEYNOTE-942 trial evaluated addition of intismeran to pembrolizumab in patients with resected stage IIIB-IV cutaneous melanoma. Five-year outcomes of the trial have now been published. Eligible patients were randomized 2:1 to receive 9 doses of intramusculare intismeran 1 mg once every three weeks plus 18 doses of intravenous pembrolizumab 200 mg once every three weeks (n=107) or 18 doses of intravenous pembrolizumab 200 mg once every three weeks (n=50). Primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS) and safety. At data cutoff, median follow-up was 60.3 months (range 50.5-76.4). Intismeran plus pembrolizumab continued to prolong RFS (HR 0.510; 95% CI 0.294-0.887) and DMFS (0.411; 0.200-0.843) with a favorable trend in overall survival (0.471; 0.165-1.345) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. The authors conclude that after 5 years of follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.