zolbetuximab-clzb and CLDN18
About the Drug
VYLOY® (zolbetuximab-clzb) is a monoclonal antibody used in combination with fluoropyrimidine- and platinum-containing chemotherapy to treat gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2-positive. The drug is supplied as a lyophilized powder for intravenous infusion. The recommended dosing regimen begins with a loading dose of 800 mg/m² followed by 600 mg/m² every 3 weeks (or 400 mg/m² every 2 weeks) when combined with standard chemotherapy such as CAPOX or mFOLFOX6. The treatment continues until disease progression or unacceptable toxicity. Common adverse effects include nausea, vomiting, fatigue, decreased appetite, and infusion-related reactions
About the Gene
The CLDN18 gene encodes claudin-18, a member of the claudin family of transmembrane proteins that are essential for maintaining tight junction integrity in epithelial cells. Two isoforms are expressed from this gene: claudin-18.1 in pulmonary tissue and claudin-18.2 in gastric mucosa. Under normal conditions, claudin-18.2 is restricted to differentiated gastric epithelial cells and is not accessible to circulating antibodies. In gastric and gastroesophageal junction adenocarcinomas, cellular transformation often results in loss of tight junction integrity and surface exposure of claudin-18.2, allowing targeted monoclonal antibodies such as zolbetuximab to bind.
About the Drug-Gene Interaction
Zolbetuximab-clzb exerts its therapeutic action by binding to the CLDN18.2 protein expressed on the surface of tumor cells. Once bound, the Fc region of the antibody recruits immune effector cells and complement proteins that mediate cell lysis and apoptosis of CLDN18.2-positive cells.
Provider Information
The links below provide access to important articles and information relative to zolbetuximab-clzb. The links are to external websites and will be checked regularly for consistency.
Sources
Lexicomp Online [Internet]. Hudson (OH): Wolters Kluwer. Zolbetuximab-clzb; [updated 2025 Oct 30; cited 2025 Nov 11]. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7520284.