Luciane Tsukamoto Kagohara

Survival outcomes in ASQ versus PDAC

Pathologic and molecular features

Neoadjuvant chemotherapy regimens in spatial transcriptomics cohort

Full statistics for pathway enrichment analysis of ASQ versus PDAC

Tissue sampling sites in FoundationOne cohort

Full statistics for differential gene expression analysis of ASQ versus PDAC

Full statistics for differential gene expression analysis of squamous versus glandular regions in ASQ

Full statistics for pathway enrichment analysis of squamous versus glandular regions in ASQ

Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions over a decade-plus, offering a window for interception in high-risk individuals, but current surveillance detects a minority of precursors. Mutant KRAS (mKRAS) is present in most PDACs and their precursors, making it an appealing target for immune-based interception. We conducted a phase I, first-in-human study of a peptide vaccine targeting 6 common KRAS mutations (mKRAS-VAX) in 20 individuals with hereditary PDAC predisposition and a radiographic pancreatic abnormality (NCT05013216) to assess safety, immunogenicity, and T-cell persistence. Adverse events were grade 1 to 2. Vaccination elicited a significant mKRAS-specific T-cell response in 18 of 20 (90%) participants. Longitudinal T-cell receptor sequencing demonstrated persistence of vaccine-induced mKRAS-specific clonotypes for up to 2 years. Over a median follow-up of 16.5 months, no participants developed PDAC. These findings demonstrate that mKRAS-VAX is safe and generates durable T-cell responses, which support the advancement of mKRAS-targeted vaccination for PDAC interception. Significance: In high-risk individuals with hereditary predisposition to PDAC, a first-in-human peptide vaccine targeting mKRAS (mKRAS-VAX) was safe and elicited durable T-cell responses, supporting further development of mKRAS-targeted vaccination for immune interception for pancreatic precancers.