Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial

2026-02-10

In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. Co-primary endpoints include safety and maximal percent change of IFNγ-producing mutant KRAS T cell responses in the blood within 17 weeks. Secondary endpoints include disease-free survival, overall survival, and maximal percent change of IFNγ-producing mutant KRAS T cell responses at any time after vaccination. Vaccine-related adverse events are grade 1-2. 11/12 and 10/12 patients generate a significant increase in average T cell response to 6 mutant KRAS antigens and tumor-specific response, respectively. Immunophenotyping demonstrate Th1 CD4 central memory and effector memory T cells, and CD8 effector memory T cells at a lower frequency. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).

Full text

DOI https://doi.org/10.1038/s41467-026-68324-4