A mutant KRAS peptide vaccine cleared its first-in-human safety and immunogenicity bar in high-risk pancreatic cancer cohorts, according to Phase I data published in Cancer Discovery. Investigators administered mKRAS-VAX to 20 participants with hereditary predisposition or concerning pancreatic imaging findings (NCT05013216), observing grade 1–2 adverse events and mKRAS-specific T-cell responses in 18 of 20 patients (90%). The immune signal persisted: longitudinal TCR sequencing tracked vaccine-induced mKRAS-specific clonotypes for up to two years. After a median follow-up of 16.5 months, none of the participants developed pancreatic ductal adenocarcinoma, while some radiographic precursor lesions shrank or stopped progressing, supporting a proof-of-concept for interception rather than treatment. The study frames PDAC prevention as a longer-window clinical problem, aiming to activate immune surveillance against a high-frequency driver in more than 90% of tumors. The next steps will focus on scaling cohorts and defining what immune kinetics best correlate with durable risk reduction.