Abstract 2964: SCR-A002, a novel FGFR2b-targeting ADC for solid tumors

Abstract Background: FGFR2b (fibroblast growth factor receptor 2 IIIb), an isoform of transmembrane tyrosine kinase FGFR family, is overexpressed in various cancers, including gastric, esophageal, breast, hepatocellular, pancreatic, ovary, uterine, cervical, endometrial, lung, colorectal cancers. Bemarituzumab (FPA144) is an afucosylated humanized IgG1 monoclonal antibody targeting FGFR2b with enhanced ADCC activity, which had promising clinical efficacy in phase 2 study of FGFR2b-selected gastric or gastroesophageal junction adenocarcinoma. Simcere Zaiming has developed a potential first-in-class FGFR2b-targeting ADC (SCR-A002) at IND-enabling status, displaying significantly superior anti-tumor potency compared to Bemarituzumab. Methods: Using hybridoma technique, anti-FGFR2b antibody was generated from immunization of FGFR2b protein in mice. SCR-A002 was comprised of a humanized anti-FGFR2b IgG1 monoclonal antibody conjugated through a cleavable linker to proprietary TOPO1 inhibitor payload (DAR 8). Binding activity and cytotoxicity were assessed in FGFR2b+ tumor cell line. And anti-tumor efficacy was evaluated in several CDX and PDX models. Results: SCR-A002 specifically bound to FGFR2b on tumor cells and could be internalized, and the TOPO1 inhibitor could be cleaved intracellularly and then exhibited potent cytotoxicity to tumor cells. And tumor regression was achieved after single-dose administration of SCR-A002 in different FGFR2b expression level CDX and PDX models, even with big-size tumor or Bemarituzumab resistance. Conclusion: SCR-A002 showed remarkable anti-tumor efficacy in preclinical data, suggesting that SCR-A002 is expected to provide a new treatment option as single agent or combo with SoC for patients with FGFR2b-overexpressing solid tumor. Citation Format: Yayuan Fu, Yuanjie Ge, Xiaohui Shao, Qi Deng, Chunlei Xia, Renhong Tang. SCR-A002, a novel FGFR2b-targeting ADC for solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2964.