Abstract LB-002: A novel c-Met/EGFR bispecific targeting antibody drug conjugate for NSCLC

Abstract

c-Met and EGFR are both widely and highly expressed, share and cross talk common signaling pathways in a variety of carcinomas including lung, breast, ovary, kidney, colon, thyroid, liver, and gastric carcinomas. Therapeutics like tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, targeting EGFR and c-Met are on the cutting-edge of cancer therapy. In preclinical studies and clinical trials, though these anti-c-Met and EGFR therapeutics showed promising anti-tumor activities but usually not sufficient for sustained treatment efficacy, their individual efficacies are limited due to the development of resistance. c-Met amplification has been considered to be a major escape route for EGFR-targeted therapies. We believe that antibody drug conjugates (ADCs) offer the promise and potential of delivering potent anti-tumor activity with the advantage of reduced side effects. We generated a novel bispecific antibody drug conjugate containing a proprietary human anti-c-Met antibody and anti-EGFR antibody, and a potent toxin by our novel C-lock conjugation method. The conjugate retained high binding affinity and targeting both c-Met and EGFR on tumor cell surface. The ADC showed potent cell killing in a lower nM range in a variety of c-Met and EGFR positive cell lines in vitro and strong in vivo anti-tumor efficacy in several c-Met and EGFR positive human NSCLC xenograft models without significant toxicity. The in vivo anti-tumor growth efficacy of bispecific c-Met/EGFR targeting antibody conjugates is superior to either single anti-c-Met or EGFR ADC.

Citation Format: Gang Chen, Lingna Li, Pia Muyot, Edwige Gros, Yanliang Zhang, Yingqing Sun, Hong Zhang, Yanwen Fu, Alice Lee, Jian Cao, Gunnar Kaufmann, Zhenwei Miao. A novel c-Met/EGFR bispecific targeting antibody drug conjugate for NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-002. doi:10.1158/1538-7445.AM2015-LB-002