zanidatamab + fluorouracil + leucovorin + oxaliplatin + bevacizumab

This is a combination regimen consisting of **zanidatamab**, **fluorouracil**, **leucovorin**, **oxaliplatin**, and **bevacizumab**. - **Zanidatamab** is a humanized bispecific monoclonal antibody that targets two distinct epitopes on the HER2 receptor, leading to potent HER2 signaling blockade and antibody-dependent cellular cytotoxicity[2][7]. - **Fluorouracil** (5-FU) is a pyrimidine antimetabolite that inhibits thymidylate synthase, resulting in impaired DNA synthesis in rapidly dividing cells. - **Leucovorin** (folinic acid) stabilizes the binding of fluorouracil to thymidylate synthase, enhancing the efficacy of 5-FU. - **Oxaliplatin** is a platinum-based cytotoxic agent that forms DNA crosslinks, inhibiting DNA replication and transcription. - **Bevacizumab** is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), thereby blocking tumor angiogenesis. This multi-agent combination targets both HER2 signaling and DNA synthesis, as well as tumor vasculature, and is under investigation or used in clinical protocols for advanced HER2-positive gastroesophageal adenocarcinoma. Based on available public clinical trial data and literature, such regimens are mainly under evaluation for first-line or later-line metastatic or locally advanced gastric, gastroesophageal, or esophageal adenocarcinoma with HER2 overexpression[1][7][3].