A Tri-specific EGFR/cMet/VEGF Antibody Demonstrates Potent Multi-Mechanistic Activity in Preclinical Triple-Negative Breast Cancer Models.

Triple negative breast cancer (TNBC) is a cancer with significant unmet medical needs and comprises 10-15 % of all breast cancers and 15-20 % of advanced breast cancers due to the limited therapeutic options. Many TNBC tumors are driven by aberrant activities of epidermal growth factor receptor, mesenchymal epithelial transition factor (cMet), and vascular endothelial growth factor (VEGF). We demonstrated how TAVO412, a tri-specific antibody that recognized cMet, dual epitopes of EGFR, and VEGF could elicit antitumor activity in TNBC. TAVO412 showed inhibition of EGFR- and cMet- mediated tumor proliferation, enhanced Fc-mediated effector functions, and suppression of angiogenesis. The avidity of the dual-epitope based anti-EGFR and anti-cMet design had better signaling inhibition and cytotoxicity against EGFR-low expressing tumor cell lines than the JNJ-61186372 analogue, a marketed EGFR/cMet bispecific antibody . Furthermore, TAVO412 exhibited anti-tumor activities in multiple TNBC cell line-derived xenograft models. Overall, TAVO412 demonstrated great preclinical utility against TNBC.