zolbetuximab + nivolumab + oxaliplatin + leucovorin + fluorouracil

A combination regimen under clinical investigation for first-line treatment of **CLDN18.2-positive, HER2-negative advanced or metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma**. - **Zolbetuximab**: Chimeric IgG1 monoclonal antibody targeting Claudin 18.2, initiating tumor cell death mainly through **antibody-dependent cellular cytotoxicity (ADCC)** and **complement-dependent cytotoxicity (CDC)**. - **Nivolumab**: Human IgG4 monoclonal antibody targeting **programmed cell death protein 1 (PD-1)**, functioning as a **checkpoint inhibitor**, restoring anti-tumor immune activity. - **Oxaliplatin**: Platinum-based small molecule cytotoxic agent that forms DNA cross-links and causes apoptosis. - **Leucovorin (folinic acid)**: Enhances antitumor effect of 5-fluorouracil (fluorouracil) by stabilizing the binding of active metabolites to thymidylate synthase. - **Fluorouracil**: Pyrimidine analog that inhibits **thymidylate synthase**, blocking DNA synthesis and function. Mechanistically, this regimen combines **targeted therapy**, **immunotherapy**, and **cytotoxic chemotherapy** for synergistic effect. The combination is currently studied in phase 2 (ILUSTRO trial) for advanced G/GEJ adenocarcinoma[1][5].

Brand names

Vyloy (for zolbetuximab)Opdivo (for nivolumab)Eloxatin (for oxaliplatin)

Other names

mFOLFOX6 (regimen component name for oxaliplatin, leucovorin [folinic acid], and fluorouracil)