Zanidatamab (Zihera)
Mechanism of action
From the NCI Drug Dictionary: A humanized, immunoglobulin G1 (IgG1) bispecific monoclonal antibody that targets two different non-overlapping epitopes of the human tumor-associated antigen (TAA) epidermal growth factor receptor 2 (HER2), ECD2 and ECD4, with potential immunomodulating and antineoplastic activities. Upon administration, zanidatamab targets and binds to the two distinct HER2 domains on the tumor cell surface. This results in dual HER2 signal blockade, HER2 clustering, receptor internalization and downregulation. This inhibits HER2 activation, HER2-mediated signaling and HER2-mediated tumor cell growth. The specific binding of zanidatamab to tumor cells and HER2 aggregation also activates various immune-mediated responses, and induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP) against tumor cells that overexpress HER2.
Diseases for which it is used
History of changes in FDA indication
- 2024-11-20: Granted accelerated approval for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test. (Based on HERIZON-BTC-01)
Also known as
- Generic name: zanidatamab-hrii
- Brand name: Zihera