Abstract 6364: The bispecific antibody KA-3006 against both EGFR and MET surpasses amivantamab in efficacy

Abstract

Abstract A bispecific antibody (BsAb) like amivantamab, which targets both the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) by blocking downstream pathways, has been proven to overcome resistance to targeted therapies, including EGFR inhibitors, in patients with various cancers. In this study, we developed a bispecific antibody, KA-3006, targeting both EGFR and MET using our common light chain antibody discovery platform. KA-3006 has a regular antibody structure with an identical light chain, developed through knob-into-hole technology. It exhibits high affinity for MET and relatively low affinity for EGFR. KA-3006 specifically blocks both the binding of EGF to EGFR and HGF to MET with higher efficiency than amivantamab, resulting in the blockade of downstream signaling from EGFR and MET. In comparison to amivantamab, KA-3006 demonstrates a faster internalization rate when binding to the surface of tumor cells expressing both EGFR and MET. KA-3006 showed superior antitumor activity over amivantamab in the HCC827-HGF in vivo model. Additionally, KA-3006 has a half-life of more than five days in the blood of Balb/c mice. Finally, we assessed the developability of this BsAb with different treatments such as high concentration, low pH, repeated freezing and thawing, and high temperature, and KA-3006 showed neither aggregation nor degradation. In conclusion, the BsAb KA-3006, developed with our common light chain antibody discovery platform, is a promising pre-clinical candidate drug for the treatment of various solid cancers with overactivated EGFR and MET signaling, and it holds potential for developing ADCs targeting both EGFR and MET. Citation Format: Guojin Wu, Jiabei Liang, Hao Peng, Feng Hao, Tongtong Liu, Jinying Ning. The bispecific antibody KA-3006 against both EGFR and MET surpasses amivantamab in efficacy [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 6364.