126P Combination of oncolytic viruses, radiation therapy, and immune checkpoint inhibitor treatment in a breast cancer model

which may amplify the innate and adaptive immune response within an immunosuppressive tumor microenvironment.We conducted preclinical studies to evaluate the anti-tumor activity of EO-3021 with an anti-PD1 or VEGFR2 inhibitor.Methods: Mice bearing NUGC4-hCLDN18.2 gastric tumors (CrownBio) were treated with a ramucirumab surrogate, DC101 (BioXCell; 20 mg/kg twice-weekly), EO-3021 (2 mg/kg once-weekly), or the combination.Mice bearing syngeneic MC38-B-hCLDN18.2tumors (Biocytogen) were treated with an anti-PD1 (BioXCell; 4 mg/kg twice-weekly), EO-3021 (7.5 mg/kg once-weekly), or the combination.An additional study was conducted to assess frequency and durability of complete responses (CRs) of EO-3021 + anti-PD1.Results: EO-3021 + DC101 exhibited superior tumor growth inhibition (TGI: 88.2%) over EO-3021 (TGI: 20.1%; p < 0.0002) or DC101 (TGI: 59.2%; p < 0.0001).EO-3021 + anti-PD1 (TGI: 79.9%) displayed synergistic anti-tumor activity vs. EO-3021 (TGI: 33.8%; p < 0.0008) or anti-PD1 (TGI: 25.0%; p < 0.0001).CRs were observed with EO-3021 (6/12 mice, 50%), anti-PD1 (2/12 mice, 17%) and the combination (11/12 mice, 92%).An update on durability of CRs, details on the immune infiltrate in mice from the EO-3021 + anti-PD1 study, and comparisons to the ADCC/CDC-inducing CLDN18.2 mAb, zolbetuximab, will be presented.Conclusions: Each of the combinations provided a more robust anti-tumor response compared to the single agents.Results from preclinical studies support the planned clinical evaluation of EO-3021 in combination with ramucirumab or a PD1 inhibitor.