A PHASE I trial of a pancreatic cancer vaccine targeting mutant KRAS has demonstrated durable immune responses and promising survival outcomes in patients with minimal residual disease following standard treatment. The AMPLIFY-201 study evaluated ELI-002 2P, a lymph node-targeted amphiphile vaccine incorporating mKRAS G12D and G12R peptide antigens with the amphiphile-adjuvant CpG-7909, in 25 participants, including 20 with pancreatic cancer and 5 with colorectal cancer.
At a median follow-up of 19.7 months, efficacy outcomes were strongly associated with the magnitude of mKRAS-specific T cell responses. Patients achieving more than a 9.17-fold increase over baseline in T cell activity experienced median radiographic relapse-free survival that was not reached, compared with 3.02 months in those with lower responses (HR=0.12, P=0.0002). Median overall survival was also not reached in the high-response group, compared with 15.98 months in the lower-response group (HR=0.23, P=0.0099).
The vaccine induced both CD4+ and CD8+ T cell subsets in 71% of evaluable patients, with immunogenicity persisting over time. Notably, 67% of patients exhibited antigen spreading, generating T cell responses against additional tumor-specific antigens not included in the vaccine formulation. This suggests that the approach may expand the breadth of antitumor immunity beyond the targeted KRAS mutations.
The findings indicate that lymph node-targeted amphiphile vaccination can drive robust and sustained immune responses against oncogenic driver mutations, potentially translating into improved clinical outcomes for patients with pancreatic or colorectal cancer following locoregional therapy. The results support further investigation in larger, controlled trials to determine long-term efficacy and potential integration into adjuvant treatment strategies.
Reference:
Wainberg ZA et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. Nat Med. 2025. doi:10.1038/s41591-025-03876-4