<p>Cellular immunity, mediated by tumor antigen-specific CD4⁺ and CD8⁺ T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (<i>n</i> = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.7 months, efficacy correlated with mKRAS-specific T cell responses above or below a threshold 9.17-fold increase over baseline, with median radiographic relapse-free survival not reached, versus 3.02 months (hazard ratio (HR) = 0.12, <i>P</i> = 0.0002) and median overall survival not reached versus 15.98 months (HR = 0.23, <i>P</i> = 0.0099). Seventy-one percent of evaluable patients induced both CD4⁺ and CD8⁺ subsets, with sustained immunogenicity. Following ELI-002 2P treatment, antigen spreading was observed in 67% of patients, with increased T cells reactive to personalized, tumor antigens absent from the ELI-002 2P vaccine. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer. ClinicalTrials.gov registration: <a href="https://clinicaltrials.gov/study/NCT04853017?term=NCT04853017&amp;rank=1">NCT04853017</a>.</p>