Zanidatamab also showed significantly greater in vitro ligand-independent and EGF-driven growth inhibition compared to trastuzumab and tras + pert in cell lines including esophageal, gastric, lung, and breast cancer. (Fig. 6, Supplementary Tables 7, 9) Moreover, cell intrinsic antitumor MOAs including HER2 downregulation, internalization, and pHER3 and pAKT inhibition likely contribute to the antitumor activity observed with zanidatamab in vitro and in vivo. The gene discussed is ERBB2; the disease is breast carcinoma.