Zolbetuximab-clzb: Targeting Claudin 18.2 in Advanced Gastric and Gastroesophageal Adenocarcinoma

Objective: To review the pharmacology, efficacy, and safety of zolbetuximab for the treatment of adults with HER2 negative gastric (GC) or gastroesophageal junction (GEJ) adenocarcinomas whose tumors are claudin 18.2 (CLDN18.2)-positive. Data sources: A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and studies from ClinicalTrials.gov between 2003 and February 2024. Keywords included zolbetuximab, IMAB362, claudiximab, claudin 18.2, gastric, and gastroesophageal junction cancer. Data extraction: All applicable publications, package inserts, meeting abstracts, and clinical trials with zolbetuximab were reviewed. Data synthesis: Zolbetuximab is a novel chimeric monoclonal antibody which targets the tight junction protein CLDN18.2. In 2 phase III clinical trials (SPOTLIGHT, GLOW), zolbetuximab when combined with a fluoropyrimidine-containing regimen, significantly improved progression free survival and overall survival in a frontline setting in HER2 negative patients with GC/GEJ adenocarcinomas that express CLDN18.2. The most common adverse reactions of any grade in patients receiving zolbetuximab with chemotherapy were nausea, vomiting, fatigue, decreased appetite, and diarrhea. Relevant to patient care and clinical practice in comparison with existing drugs: Assessment of PD-L1 and CLDN18.2 will assist clinicians in therapeutic decision selection with immune checkpoint inhibitors and zolbetuximab addition to chemotherapy in a frontline setting. Conclusion: The addition of zolbetuximab to a fluoropyrimidine based chemotherapy regimen in highly expressed CLDN18.2 GC/GEJ tumors is associated with improved survival.