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

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Background 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. Methods 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). Results 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. Conclusions 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. Trial Registration NCT05726864. Ethics Approval 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’. Consent All patients provided written informed consent.

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