The Landscape of Clinical Trials for Claudin18.2-Positive Gastric Cancer

OBJECTIVES: Gastric cancer continues to pose a notable global health challenge, with advanced-stage disease carrying a guarded prognosis. Claudin-18.2 (CLDN18.2), as a member of the Claudin protein family, plays a crucial role in maintaining gastric mucosal tight junctions and has emerged as a promising therapeutic target. To summarize the current clinical trial status of CLDN18.2-targeted drugs for gastric cancer and support related research and development efforts, this study systematically analyzed the global landscape of clinical trials focusing on CLDN18.2 in gastric cancer. METHODS: We searched for clinical trials targeting CLDN18.2-positive gastric cancer using the Citeline Pharma Intelligence (TrialTrove database) and analyzed them across multiple dimensions, including trial number, phase, status, geographical distribution, and primary tested drug. RESULTS: Through strict screening procedures, 143 clinical trials were finally included in this study. Research into CLDN18.2-positive gastric cancer is advancing fast, with a marked increase in trials since 2021. Most trials (69.93%) remain in early-phase exploration (phase I/I-II). Phase II and III trials, however, have increased as initial data show promise. Currently, 2 phase IV trials, both investigating zolbetuximab, have been initiated. Geographically, trial activity is concentrated in East Asia, North America, and Europe, with China leading in both independent and collaborative efforts, followed by the United States, which maintains the broadest international partnership network. For types of primary tested drugs, monoclonal antibodies (32.17%), antibody-drug conjugates (26.57%), and CAR-T therapies (23.08%) are the most common. Other drugs like bispecific antibodies, BiTEs, AOCs, and CAR-NK cells also point to continuous innovation in this field. CONCLUSIONS: CLDN18.2 has become a major new target in gastric cancer targeted therapy. Its clinical trials and development are advancing quickly, with various types of drugs available. In the future, more released data may make treatment strategies better and give new treatment options to gastric cancer patients.