Abstract 5300: BH3120, PD-L1 X 4-1BB bispecific antibody, plus PD-1 antagonist results in synergistic anti-tumor efficacy with excellent safety profile

Abstract

Abstract BH3120 is a clinical stage PD-L1 binding dependent 4-1BB agonist with moderate affinity against 4-1BB. In multiple preclinical evaluations, BH3120 decoupled T cell modulation in TME from that in normal tissues, indicating potential decoupling of efficacy from safety concerns. 4-1BB agonism improves T cell functions in TME, combining BH3120 and PD-1 antagonist shows dose dependent and complete control of established tumor burden with bi-directionally synergistic mechanism: Blockade of PD-1 increases the expression and exposure of surface PD-L1, providing BH3120 more chance to form immune clusters in the tumor environment. In the meantime, increased PD-1 induced by BH3120 can be blocked by PD-1 antagonist. This bi-directional mechanism results in rapid eradication of tumor tissues shortening the time to regression, indicating potentially fast control of tumor burden and associated symptoms. With the characteristics decoupling co-stimulatory activity in TME from that in normal tissues, BH3120 either as a monotherapy or in combination with PD-1 antagonist was not associated with liver toxicity and other concerns in relation to excessive modulation of immune cells systemically. Safety profile and clinical signs with BH3120 are being investigated in early-stage clinical trials as a monotherapy and in combination with a PD-1 antagonist. Citation Format: Jun Wang, Jing Wang, Yang Liu, Jiangcheng Xu, Jiawang Liu, Kyoungwoo Lee. BH3120, PD-L1 X 4-1BB bispecific antibody, plus PD-1 antagonist results in synergistic anti-tumor efficacy with excellent safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5300.