Zanidatamab is a humanized, bispecific monoclonal antibody that targets two distinct extracellular domains of the HER2 receptor, approved by the FDA for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC).
Zanidatamab binds to both the juxtamembrane and dimerization domains of HER2, resulting in receptor clustering, internalization, and downregulation.
This dual binding drives multiple antitumor mechanisms:
including inhibition of HER2 dimerization and signaling, induction of complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), leading to tumor cell death.
Clinically, zanidatamab has demonstrated efficacy and a manageable safety profile in HER2-positive biliary tract, breast, and gastroesophageal cancers, both as monotherapy and in combination with chemotherapy.
The recommended dosing for BTC is 20 mg/kg intravenously every two weeks, with premedication to reduce infusion reactions.