1317 AMPLIFY-7P Phase 2: T cell responses induced by ELI-002 7P, a lymph node-targeted amphiphile therapeutic cancer vaccine in patients with KRAS mutated pancreatic ductal adenocarcinoma

Background AMPLIFY 7P is a first-in-human Phase 1/2 trial of ELI-002 7P immunotherapy as adjuvant treatment for mutant Kirsten rat sarcoma (mKRAS) PDAC subjects with high relapse-risk. ELI-002 7P includes 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 amplify antigen-specific T cells. Prior ELI-002 2P Phase 1A results indicated initial safety, tolerability, and robust induction of mKRAS-specific T cell responses associated with improved disease-free survival (DFS) and overall survival (OS). 1 2 The randomized Phase 2 trial is proceeding to final DFS analysis.Methods The ongoing randomized multicenter Phase 2 cohort was designed to assess the primary endpoint of DFS and immunogenicity as an exploratory endpoint. 144 patients were enrolled from January-December 2024 and randomized 2:1 to receive ELI-002 7P (10 mg Amph-CpG, 4.9 mg Amph-Peptides 7P) or standard-of-care (observation only). Exploratory immunogenicity results are reported for evaluable patients treated with ELI-002 7P (n=90). Peripheral blood was collected longitudinally to assess mKRAS-specific T cells by direct ex vivo Fluorospot (IFNγ, GrB) and/or ICS assays (IFNγ, TNFα, IL2). Data cut-off is August 22, 2025.Results Among 90 evaluable patients treated with ELI-002 7P, 98.9% (89/90) induced mKRAS-specific T cells post-vaccination with average and median increase from baseline of 145.3-fold and 44.3-fold, respectively. 85.0% (68/80) of ICS-evaluable patients included both CD4 + and CD8+ T cell responses. Among a total of 630 potential mKRAS target antigens in the 90 evaluable patients, 540 were immunogenic post-treatment, suggesting an overall antigen response rate of 85.7%. Broad immune response to all 7 mKRAS ELI-002 7P epitopes was observed in 67.4% (60/89). No important differences in allele-specific immunogenicity were observed; >80% of patients generated a response specific to each individual KRAS epitope (eg. 86.7% G12D, 82.2% G12V, 86.7% G12R). Responses to the patient-specific KRAS mutation identified in the tumor at screening were observed in 87.6% (78/89).Conclusions Consistent with prior Phase 1 results, ELI-002 7P induced potent and functional mKRAS-specific T cell responses in nearly all treated patients, with significant expansion from baseline levels, including CD4 + and CD8+ subsets, and specificity for all 7 vaccine-encoded KRAS mutations. 80% of Phase 2 patients achieved T cell responses exceeding ~9-fold over baseline which previously correlated to DFS, OS clinical outcomes;1 2 future correlation to the Phase 2 clinical endpoints is planned following final analysis.References Wainberg Z. et al. Nature Medicine 2025. https://doi.org/10.1038/s41591-025-03876-4 Pant S. et al. Nature Medicine 2024;30:531–542.Ethics Approval ELI-002-201 Central IRB approval was obtained from WCG (ID#s 1-1576618-1, 1-1576861-1, 1-1591601-1, 1-1636969-1, 1-1649212-1, 1-1750314-1, 1-1765970-1, 1-1778270-1, 1-1788990-1, 4-1660517-1). Local IRB approvals included: Memorial Sloan Kettering Cancer Center IRB (#22-352 and 22-352A(8)), Advarra (ID#s Pro00065733 and Pro00067455), the University of Iowa IRB (ID# 202212072), Feinstein Institutes for Medical Research, Northwell Health IRB (ID# 22-0814), University of California, Los Angeles Office of the Human Research Protection Program (ID# 22-001911), Mass General Hospital Dana Farber Cancer Institute Office for Human Research Studies (ID# 2022P003064 and amendment 501742), University of Pennsylvania IRB (ID# 852790), Mayo Clinic IRB (ID# 23-002402), UTSW Medical Center IRB (ID# STU-2022-0682), Medical College of Wisconsin IRB (ID# PRO00044877), Vanderbilt University Medical College IRB (ID# 221708), University of Miami IRB (ID# 20231247) and Cedars-Sinai IRB (ID# STUDY00003283). All participants signed informed consent before taking part in the trial.