A fully human bispecific antibody (bsAb) targeting HER3 and MET was generated using RenLite® mice, known for producing fully human antibodies. This bsAb effectively bound to HER3 and MET antigens, showing enhanced internalization activity in cell lines expressing these targets. The bsAb was conjugated to two distinct payloads, vcMMAE and BLD1102, for evaluation in vivo. Both conjugates demonstrated strong anti-tumor activity in cell-derived xenografts (CDX) of gastric cancer and patient-derived xenograft (PDX) models of pancreatic and colorectal cancers. These promising preclinical results suggest that the bsADC, BCG022, could be a novel and effective treatment for tumors co-expressing HER3 and MET.