Abstract 3897: A novel c-Met targeting antibody drug conjugate for NSCLC

Abstract

Abstract c-Met, the proto-oncogene transmembrane receptor tyrosine kinase, is involved in cell proliferation, survival, motility, and invasion in normal and tumor cells. It is widely expressed and associated with poor prognosis in breast, lung, liver, kidney and brain cancers. Hepatocyte growth factor (HGF) is the only known ligand of c-Met, also found in many tumors and cancers where activity is driven by the c-Met receptor. c-Met is accepted as an attractive anti-cancer target, but the development of cancer therapy targeting c-Met receptor or kinase remain very challenging. Clinical development of c-Met/HGF targeting antibodies has shown initial evidence of clinical efficacy but failed in phase III. Small molecule inhibitors often suffer from selectivity issues. Antibody drug conjugates (ADCs) which combine an antibody with highly potent cytotoxic agents, becomes an attractive approach against c-Met overexpressing cancers such NSCLC. We have identified an anti-c-Met antibody STI-0602 and generated ADCs from a panel of cytotoxic agents such as microtubulin inhibitor and DNA damaging agents. ADCs retained the binding to c-Met receptor and showed potent cell killing in a variety of c-Met-positive cell lines. ADCs also showed in vivo efficacy in a panel of c-Met-positive human NSCLC xenograft models like A549, H292, EBC-1, HCC827 and H1993, which suggest a potential therapy for c-Met overexpressing lung cancer and other cancers. Citation Format: Lingna Li, Cathrine Fells, Julia Guo, Pia Muyot, Edwige Gros, Yanliang Zhang, Yingqing Sun, Hong Zhang, Yanwen Fu, Tong Zhu, Jian Cao, Gunnar Kaufmann, Gang Chen, Zhenwei Miao. A novel c-Met targeting antibody drug conjugate for NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3897.