CLDN18 (Claudin 18)

These results suggest that chemotherapeutic agents upregulate CLDN18.2 in GC cells at least in part through cell cycle arrest, and support combining zolbetuximab with chemotherapy and/or CDK inhibitors for GC treatment.

P3, N=464, Active, not recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Active, not recruiting

P3, N=600, Not yet recruiting, NingBo Junyan Hongshi Biosciences Co., Ltd

Along with these developments in drug therapy, more therapies directed at CLDN18.2, HER2, MSI, EGFR, HER3 and trophoblast cell-surface antigen 2 (TROP2) are underway. Here we review future areas in advanced GAC, including zanidatamab's potential role in HER2-positive advanced GAC and deciphering the abundance of anti-CLDN18.2, extending beyond investigative therapies.

FGFR2b positivity was observed in 14.1% of patients and was evaluated descriptively due to limited case numbers. CLDN18.2 expression may represent a clinically relevant prognostic biomarker reflecting aggressive tumor biology in locally advanced gastric cancer treated with neoadjuvant therapy.

Despite assay variability, even under stringent clinical trial criteria, a meaningful subset of patients may qualify for CLDN18.2-targeted therapy. These findings highlight the need for standardized testing and further clinical evaluation of CLDN18.2-directed strategies in PDAC.

P3, N=324, Recruiting, Federation Francophone de Cancerologie Digestive

P2, N=100, Recruiting, AstraZeneca

However, realizing its full potential requires addressing challenges related to tumor heterogeneity and drug resistance. Future research must focus on validating novel biomarkers and developing synergistic combination strategies to further improve patient survival.

P2/3, N=290, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Not yet recruiting --> Recruiting | Initiation date: Jan 2026 --> Apr 2026

This review outlines the evolving therapeutic landscape of gastric and gastroesophageal junction cancers, spanning perioperative immunotherapy, newly validated molecular targets, and next-generation drug development platforms. By integrating biomarker-driven strategies with innovative modalities, such as antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor-T-cell therapy, and vaccines, we highlight how precision therapeutics are reshaping treatment paradigms across resectable and advanced disease.

In Japanese patients, zolbetuximab plus chemotherapy improved PFS versus placebo plus chemotherapy and showed a numerical improvement in OS. These results support zolbetuximab plus chemotherapy as a potential new standard-of-care first-line option for Japanese patients with CLDN18.2-positive, HER2-negative, LA unresectable or metastatic gastric or GEJ adenocarcinoma.