Abstract LB-018: Orally active small molecule PD-L1 inhibitor demonstrating similar efficacy as Durvalumab in human knock-in MC38 model

Abstract

Abstract Cancer immunotherapy with PD-1/PD-L1 antibody drugs has made tremendous progress in clinical application. It was also recognized by the scientific community with awarding of the 2018 Nobel Price. However, the discovery of orally active, small molecule drugs targeting PD-1/PD-L1 pathway remains highly challenging. We wish to report for the first time the similar efficacy as measured by TGI between small molecule inhibitor Max-10181 and Durvalumab in the head to head test of human PD-L1 knock-in MC38 cell line in human PD-1 knock-in mice. In addition, we would also like to report the superior efficacy of Max-10181 to mouse anti-PD-1 Ab in PD-L1 expression low syngeneic mouse 4T1 model. Our data indicated that small molecule drugs may have different dependency of PD-L1 expression level. As a result, they may have different therapeutic application in clinics. Furthermore, the data related to the mechanistic aspect of these observed results will also be discussed. Citation Format: Yuguang Wang, Nong Zhang, Feilan Wang, Qiang Zhao, Zenggang Li. Orally active small molecule PD-L1 inhibitor demonstrating similar efficacy as Durvalumab in human knock-in MC38 model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-018.