Survival of patients (pts) with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal carcinoma (mCRC) treated with EO4010 + nivolumab (EO/N).

3536 Background: EO is designed to expand pre-existing memory CD8 T cells cross-reacting with tumor associated antigens (TAAs). EO is composed of microbial-derived sequences mimicking CD8 T cell HLA-A2 epitopes on 5 TAAs, BIRC5, FOXM1, UBE2C, CDC20 and KIF2C, upregulated in mCRC, and the CD4 peptide UCP2. Methods: Pts had MSS/pMMR mCRC, treated with FU, oxaliplatin, irinotecan and anti-VEGF/EGFR. Cohort (C)1 safety lead-in followed by expansion C2; pts received EO (300 μg/peptide in Montanide ISA 51 VG) q2 weeks (w) x4 then q4w + N (240 mg q2w x 3 then 480 mg q4w; C1 omitted 2 first N doses). Results: 20 pts (C1 = 3, C2 = 17), 55% female, 70%/30% ECOG 0/1, median age 58 (45-80) years, started EO + N June 2023 to March 2024. Primary tumor right sided 35%/left 35%/rectal 30%, median 2 (1-4) tumor involved organs, 55% liver mets, 65% KRAS mutated, and median 3 (1-5) prior lines of treatments. Any grade related AEs in > 2 pts: local administration site reactions (85%), asthenia (15%), and fatigue (15%); 1 related Gr 3, local administration site ulceration; 1 related SAE, N infusion related reaction. CD8 T cells (EO/TAA peptide specific tetramers staining of PBMC ex vivo) against EO found in 10/11 tested pts, cross-reactivity against TAAs in all 10 positive pts. Best response (RECIST 1.1): 1 partial response (liver mets -47%, lung mets -34%; CEA normalized), 1 stable disease (SD) (lung mets -7%; CEA -68%, CA19-9 -55%; pat died w 17 non-related myocardial infarction), and 1 SD until w 18 (withdrawn consent); 6 (30%) pts had target SD, and unequivocal progression of non-target lesions; 11 pts (55%) had progressive disease. Median PFS 1.8 months (mo) (range 1.4-10.5). 14 pts (70%) received post-study anti-cancer treatment. After a median follow-up of 14.7 mo, median overall survival (OS) 11.2 mo; 80% 6- and 39% 12-mo survival. Immune response assessed using a composite score of EO4010-specific T cell responses, measured by ex vivo tetramer assays weeks 5 to 9 of treatment (best response used), with pts stratified into high and low responders based on median score. Kaplan-Meier analysis with log-rank test showed trend towards better OS in high responders (p = 0.065). Median OS low responders 9.6 mo and not reached for high responders. Immune response magnitude showed no correlation with baseline T cell activation potential (by anti-CD3 stimulation/ELISPOT); independence indicates that EO4010-induced CD8 T cell expansion occurs irrespective of baseline T cell status. Conclusions: EO4010 + nivolumab promotes expansion of TAA specific CD8 T cells and shows good safety and interesting survival in previously treated MSS/pMMR mCRC. Data suggests a potential survival benefit associated with stronger EO4010-induced immune responses. Continued evaluation of EO is warranted; further immune testing data, and results of addition of bevacizumab to EO + N in a separate cohort are awaited. Clinical trial information: NCT05589597 .