P3, N=820, Not yet recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Jan 2026 --> Jan 2030 | Trial primary completion date: Oct 2025 --> Oct 2029

These observations suggest that gastric wall changes detectable using US are closely linked to nausea and may reflect underlying gastric injury. This report also highlights the potential of bedside US monitoring to help predict and prevent nausea during zolbetuximab therapy.

The patient was treated with six cycles of zolbetuximab-CAPOX (zolbetuximab, capecitabine, and oxaliplatin), resulting in complete regression of liver metastases and significant tumor shrinkage. Additionally, transient treatment-related gastritis observed during therapy raises questions about the effects of CLDN18.2 inhibition on gastric mucosal integrity. Further research is warranted to refine patient selection for CLDN18.2-targeted therapy and investigate its broader physiological effects.

Finally, we identify current limitations in the field, including inconsistent CLDN18.2 testing criteria, and outline prioritized future directions to optimize integration of CLDN18.2-directed therapies across gastrointestinal cancers. By looking beyond zolbetuximab and incorporating cross-platform comparison, immuno-oncology considerations, and multi-tumor context, this review provides a broad and forward-looking framework to guide clinical application and next-generation research in CLDN18.2-targeted therapy.

P1, N=10, Completed, Zhejiang Provincial People's Hospital | Recruiting --> Completed | N=30 --> 10 | Trial completion date: Jun 2027 --> Sep 2025

This study presents a case of Claudin18.2-positive advanced gastric adenocarcinoma with peritoneal metastasis treated with a multimodal regimen: HIPEC, systemic CapeOx chemotherapy, and Claudin18.2-targeted therapy (ASKB589)...At 893 days post-diagnosis, the patient remains disease-free (PFS/DFS: 893/573 days) on adjuvant capecitabine...However, the absence of cytoreductive surgery and single-case limitations necessitate validation through randomized trials. Future research should prioritize biomarker-driven HIPEC protocols (e.g., nanoparticle-enhanced Claudin18.2-targeted delivery) and dynamic monitoring of Claudin18.2 expression during therapy.

Zolbetuximab is associated with high rates of nausea and vomiting during the initial infusion, whereas ICIs are associated with risk of later-onset immune-related toxicities that can be fatal in rare cases. In considering the available evidence, our opinion is that zolbetuximab is a reasonable option for initial targeted treatment in HER2-/CLDN18.2-positive advanced G/GEJ when PD-L1 CPS score is <10 based on the reliability of biomarker testing, comparable OS, and avoidance of potentially irreversible ICI-induced immune toxicity.

Clinicians should monitor albumin levels during treatment and consider nutritional support when indicated. These findings provide important insights for optimizing patient management and ensuring safe conversion surgery planning.

P1, N=25, Recruiting, Astellas Pharma Global Development, Inc. | Initiation date: Jul 2025 --> Oct 2025

Serial PET imaging with 89Zr-labeled zolbetuximab, an anti-CLDN18.2 monoclonal antibody ([89Zr]Zr-DFO-zolbetuximab), and human IgG ([89Zr]Zr-DFO-IgG) as control (5.5-7.4 MBq) was performed 1, 3, and 6 d after injection, followed by ex vivo analysis of biodistribution... CLDN18.2 could serve as a promising biomarker for precise quantitative imaging and effective treatment of GCa and PDAC. This proof-of-concept study encourages the clinical translation of CLDN18.2 as a radiotheranostic in patients with CLDN18.2-expressing tumors.

P1, N=12, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting