Zolbetuximab: A Narrative Drug Review

Abstract Claudin-18.2 (CLDN18.2) is a tight junction protein selectively expressed in a subset of gastric and gastroesophageal junction (GEJ) adenocarcinomas, making it a promising therapeutic target. Zolbetuximab is a first-in-class chimeric IgG1 monoclonal antibody that binds to CLDN18.2-positive tumor cells and induces cell death through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Antitumor efficacy was further enhanced when combined with platinum-based chemotherapy. This review focuses on the pharmacology, pharmacokinetics, clinical applications, dosing, adverse events, and storage and administration of zolbetuximab. Data were compiled through an extensive search of databases such as PubMed, Google Scholar, ScienceDirect, and regulatory sources such as the U.S. Food and Drug Administration (FDA). Relevant search terms included “Zolbetuximab,” “CLDN18.2,” and “advanced gastric cancer.” Additional information was drawn from the clinical trial results and conference proceedings. Zolbetuximab has received FDA approval for the treatment of HER2-negative, CLDN18.2-positive advanced gastric and GEJ adenocarcinoma, supported by evidence from pivotal clinical trials, such as SPOTLIGHT and GLOW, which showed significantly improved progression-free and overall survival compared with chemotherapy alone.