EGFR and HER3 are prevalent in epithelial tumors, particularly in lung cancer where EGFR often exhibits mutations and HER3 is overexpressed in therapy-resistant patients. To combat this resistance, BCG019, a bispecific antibody-drug conjugate (bsADC) targeting both receptors was developed. This bsADC, generated using fully human bispecific antibodies from RenLite® mice, demonstrated binding across various cancer cell lines and effective internalization. Conjugated with vc-MMAE and BLD1102, it showed superior anti-tumor activity in preclinical models of NSCLC and gastric cancer, suggesting promise for treating tumors co-expressing EGFR and HER3.