Evaluating the pharmacokinetics of zolbetuximab in gastric adenocarcinoma

Introduction: Gastric adenocarcinoma (GAC) represents a heterogeneous disease making treatment advancements difficult. Recently, claudin 18.2 (CLDN18.2) has emerged as an exciting new target in GAC. Zolbetuximab, an anti-CLDN18.2 monoclonal antibody, has now been FDA approved. Areas covered: Phase 1, 2, and 3 zolbetuximab trials have been completed in GAC. Phase 3 trials evaluating zolbetuximab in combination with front-line fluoropyrimidine plus platinum therapy improved survival endpoints compared to placebo plus chemotherapy in those with high CLDN18.2 positivity (>75% of tumor cells). This led to zolbetuximab’s FDA approval in this population. Here, we review aspects of zolbetuximab’s pharmacology known at this time. Expert opinion: Zolbetuximab is one of many agents targeting CLDN18.2 under development. Zolbetuximab in combination with chemotherapy has a slight impact on high CLDN18.2 expressed GAC to chemotherapy alone. Examining how to improve upon outcomes will be of benefit. Additionally, there are GAC subsets who may have benefit from zolbetuximab but need more close examination such as those with moderate CLDN18.2 expressed tumors, low CLDN18.2 expressed tumors, and CLD18-ARHGAP fusion patients.