Phase 2 Trial: KRAS Vaccine Generates T-Cell Response in 98.9% of Resected Pancreatic Cancer Patients

The Mayo Clinic-led study enrolled 144 patients with stage 1-3 KRAS-mutated pancreatic ductal adenocarcinoma who had no detectable disease after resection and adjuvant chemotherapy. Ninety-six were randomized to the vaccine and 48 to observation. The vaccine is designed to traffic to lymph nodes and prime CD8+ T cells against mutant KRAS epitopes shared across roughly 90% of pancreatic tumors. Primary endpoint of disease-free survival was not met, with median DFS of 23.8 months versus 21.2 months. In a preplanned analysis, 98.9% of vaccinated patients developed KRAS-specific T-cell responses; those reaching a greater than ninefold increase showed longer DFS. Circulating tumor DNA negativity at baseline emerged as a potential enrichment biomarker. The trial design was phase 2 randomized but underpowered for modest survival differences and relied on exploratory immune correlates rather than a validated surrogate. Next steps require a phase 3 study restricted to ctDNA-negative patients with adequate powering for the observed immune-response threshold. This observational signal cannot yet establish causality between T-cell magnitude and clinical outcome.