Abstract

Abstract 4-1BB (CD137, TNFSF9) is a promising co-stimulatory signaling mediator of T cells and NK cells, and agonistic monoclonal antibodies targeting 4-1BB are under clinical investigations aiming to observe sufficient and prolonged anti-tumor efficacy. However, these trials have resulted in limited efficacy or safety, and different bispecific approaches are being explored to improve the profiles. BH3120, a bivalent bispecific antibody generated by Pentambody(TM) platform targeting 4-1BB and PD-L1 simultaneously, demonstrates strong and prolonged antitumor efficacy as monotherapy in in vivo studies, and favorable safety profiles up to 200mg/kg/dose in non-human primates. Moreover, combination of BH3120 with an immune checkpoint inhibitor shows synergistically enhanced anti-tumor efficacy. Supported by these results, IND enabling studies of BH3120 are on-going and clinical evaluations are planned from later in 2022. Citation Format: Jiangcheng Xu, Yang Liu, Jing Wang, Fei Fan, Haitao Gu, Lanxin Zhang, Jun Wang, Ding Song, Ailong Guo, Hongjuan Zhang, Kaixuan Su, Jiaojiao Su, Lijuan Li, Jingmei Cai, Aihong Zhang, Jiawang Liu, Kyoungwoo Lee. BH3120: A novel bispecific antibody targeting 4-1BB and PD-L1 with well balanced efficacy and safety profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5605.

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