zanidatamab + fluorouracil + cisplatin

Zanidatamab + fluorouracil + cisplatin is a combination regimen under clinical investigation for the treatment of HER2-positive solid tumors, particularly advanced or metastatic gastroesophageal adenocarcinomas and biliary tract cancers. Zanidatamab is a humanized bispecific monoclonal antibody that targets two distinct non-overlapping domains (extracellular domains 4 and 2) of the HER2 protein. Its mechanisms of action include strong HER2 signal blockade, HER2 protein removal from the cell surface, immune-mediated cytotoxicity (antibody-dependent cellular cytotoxicity [ADCC] and antibody-dependent cellular phagocytosis [ADCP]), complement-dependent cytotoxicity (CDC), inhibition of HER2 dimerization and intracellular signaling, and HER2 internalization and degradation. When combined with standard cytotoxic chemotherapies like fluorouracil (a pyrimidine analog inhibiting thymidylate synthase and DNA synthesis) and cisplatin (a platinum compound causing DNA crosslinking and apoptosis), the regimen aims to synergistically attack HER2-expressing tumors through both targeted and broad cytotoxic mechanisms[1][2][4][5][7].