JCO at ASCO 2026: Individualized Neoantigen Therapy Plus Pembrolizumab in Melanoma

Individualized neoantigen therapy (INT) combined with pembrolizumab significantly improves long-term outcomes for patients with high-risk resected melanoma compared to pembrolizumab alone. Five-year data from the Phase 2b KEYNOTE-942 study, discussed by JCO Associate Editor Dr. McArthur, reveals impressive hazard ratios of 0.51 for relapse-free survival and 0.41 for distant metastasis-free survival. This personalized mRNA vaccine approach, which targets up to 34 patient-specific neoantigens, demonstrates a clear biological mechanism of action through the sustained expansion of unique T-cell receptor clonotypes. While the current study focused primarily on stage 3C disease, an ongoing Phase 3 trial is expanding this investigation to stages 2B and 2C. These findings establish a proof of concept for personalized oncology vaccines and suggest a future paradigm shift where INT could be integrated into neoadjuvant settings to further reduce relapse rates in melanoma and other solid tumors.