Multinational phase 3 trial of intismeran autogene plus pembrolizumab for resected stage IIB to IV melanoma

Intismeran autogene (intismeran) is an individualized neoantigen therapy that is designed to induce new T-cell responses and expand preexisting T-cell responses against patient-specific tumor neoantigens, which may potentially improve the efficacy of adjuvant therapy in patients with melanoma. In the multinational phase 3 INTerpath-001 trial, patients with completely resected stage IIB to IV cutaneous melanoma were randomized 2:1 to receive intramuscular intismeran (n=757) or placebo (n=380) every 3 weeks for nine doses; all patients received intravenous pembrolizumab every 6 weeks for nine cycles. The primary endpoint was investigator-assessed recurrence-free survival (RFS). The median follow-up was 24.6 months. RFS rate at 24 months was 82.2% in the intismeran-pembrolizumab group and 70.0% in the placebo-pembrolizumab group (two-sided p<0.001); the piecewise hazard ration was 0.99 (95% CI 0.66-1.49) before 6 months and 0.42 (0.30-0.58) after 6 months. Distant metastasis-free survival (DMFS) rate at 24 months was 88.5% with intismeran-pembrolizumab and 80.2% with placebo-pembrolizumab (two-sided p=0.002): the piecewise HR was 1.01 (95% CI 0.58-1.79) before 6 months and 0.50 (0.34-0.73) after 6 months. Adverse events of grade 3 or higher occurred in 23.6% of the patients in the intismeran-pembrolizumab group and 20.3% of the patients in the placebo-pembrolizumab group. Eight patients (1.1%) in the intismeran-pembrolizumab group died from an adverse event; five of these deaths occurred before intismeran was administered. The authors conclude that adjuvant therapy with intismeran plus pembrolizumab significantly improved RFS and DMFS as compared with pembrolizumab alone among patients with completely resected, high-risk cutaneous melanoma.