A first-in-human Phase I study of a peptide vaccine targeting common mutant KRAS variants (mKRAS-VAX) advanced pancreatic cancer prevention by showing safety and immune activation in high-risk cohorts. The trial enrolled 20 participants with hereditary PDAC predisposition and/or radiographic pancreatic abnormalities (NCT05013216). Adverse events were grade 1–2, and 90% of participants mounted mKRAS-specific T-cell responses. With a median follow-up of 16.5 months, no participants developed PDAC. Vaccine-induced mKRAS-specific T-cell clonotypes persisted for up to two years based on longitudinal TCR sequencing, and some precancerous lesions shrank or stopped progressing. The results were published in Cancer Discovery. The study provides early clinical proof that immune interception of pancreatic cancer may be feasible in humans, aiming to reduce the reliance on surgery for transformation to invasive disease in surveillance programs.