Abstract LB021: KN-052, a novel PDL1/OX40 bispecific antibody, exhibits potent antitumor efficacy

Abstract

Abstract KN052 is a recombinant PDL1/OX40 bispecific antibody which can block PDL1 and PD1/CD80 pathway and active the OX40 signal pathway at the same time. Inhibited PDL1 can block cancer cells to evade T-cell-mediated immune responses and restores T-cell activation and antitumor responses. On the other hand, biding to OX40 which normally expressed on Treg cells can induce ADCC effect and kill the Treg cells. There is a synergistic effect between the blocking of PDL1 pathway and the activation of OX40 signal pathway in cell base assay. PBMCs from four healthy donors showed significant T cell activation effect under the stimulation of superantigen SEB, and the activity of PBMCs from three healthy donors was significantly stronger than that of two single target control antibodies alone and in combination. The anti-tumor activity of KN052 was evaluated by using hPD-L1/hOX40 humanized mouse with MC38 MCA205 syngeneic model. Significant anti-tumor effects were observed in both models in a dose-dependent manner. The HNSTD (highest non-severely toxic dose) of KN052 was determined as 30mg/kg in cynomolgus monkeys. These preclinical data demonstrated acceptable PK and safety profile of KN052 and indicated its potential in a variety of tumors. Citation Format: Ting Xu, Pilin Wang, Yang-Xin Fu, Kangping Guo, Jianjian Peng. KN-052, a novel PDL1/OX40 bispecific antibody, exhibits potent antitumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB021.