Zanidatamab (brand name Ziihera) is a bispecific, HER2-directed antibody used for the treatment of certain advanced cancers.
Zanidatamab-hrii it is indicated for adults with:
Biliary Tract Cancer (BTC): Previously treated, unresectable, or metastatic HER2-positive (IHC 3+) BTC, including gallbladder cancer and cholangiocarcinoma.
Phase 3 trials (HERIZON-GEA-01) have shown significant improvement in progression-free and overall survival for gastroesophageal adenocarcinoma.
Unlike traditional HER2 therapies that bind to one site, zanidatamab is biparatopic, meaning it binds to two non-overlapping domains of the HER2 receptor (ECD2 and ECD4).
Receptor Clustering: Facilitating the internalization and degradation of HER2.
Immune Activation: Inducing antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).
Signaling Inhibition: Preventing HER2 dimerization to block tumor growth.
Administration: It is typically administered as an intravenous (IV) infusion every two weeks.
Common Side Effects: The most frequent adverse events are and infusion-related reactions.
Other reported effects include a decrease in ejection fraction and fatigue.