1473 AMPLIFY-7P phase 1a: lymph node-targeted amphiphile therapeutic cancer vaccine in patients with high relapse risk KRAS mutated pancreatic ductal adenocarcinoma and colorectal cancer

<h3>Background</h3> AMPLIFY-7P is a first-in-human Phase 1/2 trial of ELI-002 7P immunotherapy as adjuvant treatment for subjects with high relapse-risk mutant Kirsten rat sarcoma (mKRAS) PDAC and CRC. ELI-002 7P consists of Amph-modified G12D, V, R, C, S, A and G13D mKRAS peptides with an Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). Amph-modification promotes lipid-mediated binding to albumin and direct delivery of antigen/adjuvant to lymph nodes to activate and amplify antigen-specific T cells. <h3>Methods</h3> The multicenter Phase 1a trial assessed safety, immunogenicity and antitumor activity of ELI-002 7P. 14 patients with minimal residual disease received 10 mg of Amph-CpG and 1.4 mg or 4.9 mg of Amph-Peptides 7P after locoregional treatment. Preliminary antitumor activity and safety are reported (n=13). Peripheral blood was collected longitudinally to assess specificity, polyfunctionality, and phenotype of mKRAS-specific T cells (n=12). <h3>Results</h3> ELI-002 7P was well-tolerated, with no dose-limiting toxicity, treatment related SAEs or cytokine release syndrome at either dose level. 100% of evaluable subjects (12/12) induced mKRAS-specific T cells post-vaccination as assessed by direct ex vivo Fluorospot and/or ICS assays with a median 17.5-fold increase from baseline. Higher mKRAS-specific T cell responses were observed in the 4.9 mg versus the 1.4 mg dose level, with 113.3 versus 9.3 median fold-change from baseline. Evaluation of the breadth of response to 7 mKRAS vaccine antigens revealed diverse T cell specificity, with positive responses detected to each of the KRAS mutations and 6 KRAS mutations inducing the maximum response in at least one patient. 67% of patients had balanced mKRAS-specific CD4⁺ and CD8⁺ T cell responses. mKRAS-specific T cells were cytotoxic, proliferative and secreted multiple cytokines. Antigen spreading to non-immunizing neoantigens was observed in 6/6 patients evaluated in the 4.9 mg dose group. When antitumor efficacy was stratified based on the magnitude of the T cell response, median disease-free survival was not reached for patients with maximum T cell response in quartiles 2–4 versus 11 weeks for patients in the lowest quartile. Additional stratifications of disease-free survival will be shown. <h3>Conclusions</h3> ELI-002 7P was well tolerated and preliminary antitumor activity was observed with 4.9 mg Amph-Peptides 7P selected as the recommended Phase 2 antigen dose. Data indicates that this off-the-shelf lymph node-targeted vaccine induces high-magnitude immunogenicity correlated to antitumor efficacy: T cells targeting driver mutations critical for tumor survival and antigen spreading to non-immunizing antigens. The randomized Phase 2 clinical trial of ELI-002 7P in PDAC patients is ongoing. <h3>Trial Registration</h3> NCT05726864. <h3>Ethics Approval</h3> The study was approved by the local institutional review board at each study site and conducted under an FDA Investigational New Drug application or ‘IND’. <h3>Consent</h3> All patients provided written informed consent.