AMPLIFY-7P, a first-in-human safety and efficacy trial of adjuvant mKRAS-specific lymph node targeted amphiphile ELI-002 7P vaccine in patients with minimal residual disease–positive pancreatic and colorectal cancer.

2636 Background: Diverse KRAS mutations occur in 25% of solid tumors with G12D, V and R most frequent. ELI-002 7P is an expanded spectrum vaccine comprised of lymph-node targeted Amphiphile (Amph)-modified G12D, V, R, C, S, A, and G13D mutant KRAS peptides with an Amph-modified CpG oligonucleotide adjuvant designed to expand polyfunctional mutant KRAS-specific T cells. Earlier ELI-002 2P showed high rates of T cell and tumor biomarker response (both 21/25, 84%), with median relapse-free survival not reached versus 4.01 months (HR 0.14; p=0.0167) comparing patients (pts) above versus below T cell median (12.75X). Methods: This multicenter phase IA trial assessed safety, immunogenicity and preliminary antitumor activity of ELI-002 7P in pancreatic (PDAC) and colorectal pts with minimal residual disease (MRD) following standard locoregional treatment. Pts with elevated circulating tumor DNA (ctDNA) and/or serum tumor biomarker (CA19-9/CEA), and KRAS mutation were enrolled and treated with subcutaneous fixed dose Amph-CpG-7909 and 1.4 mg or 4.9 mg of Amph-Peptides 7P (Table). Safety, T cell change, and preliminary antitumor activity including biomarker reduction/clearance are reported. Results: No dose-limiting toxicities, no treatment related SAEs or cytokine release syndrome were observed, no maximum tolerated dose was identified, and the recommended phase 2 dose (RP2D) was 10.0 mg Amph-CpG-7909 with 4.9 mg Amph-Peptides 7P. Safety: all grade 1, fatigue (29%), malaise (21%), and injection site reaction (7.1%). At data cutoff Dec 18, 2023, polyfunctional mKRAS-specific T cells were observed in 100% (n=11/11). Both CD8+ and CD4+ responses were induced in 63.6% of pts (7/11), with higher median fold-change from baseline at RP2D and durable responses post-booster immunization in 100% of pts (7/7). Biomarker reductions were observed in 2/5 (40%) at the 1.4 mg Amph-Peptides 7P dose level and in 5/7 (71%) at the RP2D 4.9 mg dose level in pts with all the common G12X (D, V, R) and G13 (D) KRAS mutations; MRD clearance was observed in 1 G12V PDAC pt at 4.9mg. Conclusions: ELI-002 7P was safe with median RP2D T cell responses exceeding the prior formulation (7P median 109.2; 2P 12.75), and early indications of antitumor activity. The randomized phase II is now open in patients with pancreas cancer. Clinical trial information: NCT05726864 . [Table: see text]