Abstract 5564: QLS31901, a novel bifunctional anti-PD-L1/TGF-β fusion protein for treatment of solid tumors

Abstract Immunosuppressive pathway blocking antibodies (e.g., anti-programmed death ligand 1 [PD-L1] antibodies) are effective and feasible cancer therapy, but some patients have poor individual drug responses to this class of drugs. Simultaneous targeting other immunosuppressive pathways is therefore a novel method to enhance the efficacy. While the antitumor activity of bifunctional anti-PD-L1/transforming growth factor-β (TGF-β) fusion protein bintrafusp alfa (M7824) in preclinical studies is well known, clinical studies to date with M7824 have led to limited success. QLS31901 is another bifunctional fusion protein composed of the truncated extracellular domain of the TGF-β receptor II fused to the C-terminus of humanized anti-PD-L1 heavy chain (αPD-L1) with function as a “trap” for all three TGF-β isoforms and the blockage of PD-L1 immunosuppressive pathway. The present study demonstrated its superior antitumor activity over M7824 in a humanized MDA-MB-231 model. Furthermore, toxicology studies of QLS31901 only showed a transient interleukin 6 elevation. There were no other cytokine release and organ toxicity in cynomolgus monkeys. Overall, these data provided a rationale for an expansion cohort study of QLS31901 for the treatment of patients with solid tumors and dual blockade of TGF-β as well as PD-L1 with QLS31901 may be a promising therapy. Citation Format: Jiahua Jiang, Cuicui Han, Qi Chen, Yun Wu, Xiaodan Yan, Ping Cao. QLS31901, a novel bifunctional anti-PD-L1/TGF-β fusion protein for treatment of solid tumors [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 5564.