CLDN18.2 expression

Although circulating CAR T-cells became nearly undetectable in peripheral blood by around day 30 after infusion, CAR T-cell infiltration was still detected in resected gastric or ovarian tumor tissues months later. These findings support substantial and durable activity of CLDN18.2 CAR T-cell therapy in gastric cancer with peritoneal metastasis.

In preclinical studies, [177Lu]Lu-DOTA-SN-1A01 demonstrated significant antitumor efficacy with acceptable toxicity, which indicated a strong potential for clinical translation in GC therapy.

Herein, we summarize CLDN18.2 expression in cancer along with clinical trials of zolbetuximab and other CLDN18.2-directed therapies. Given the variability in CLDN18.2 expression within and between tumor types, biomarker-driven approaches will be critical for patient selection in clinical trials and therapeutic approaches.

P1, N=222, Recruiting, Shandong Boan Biotechnology Co., Ltd. | -> Recruiting | Phase classification: PN/A --> P1

P3, N=752, Recruiting, Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd. | Not yet recruiting --> Recruiting

Claudin-18 isoform 2 (CLDN18.2) has rapidly moved from a gastric-lineage surface antigen to an actionable therapeutic target in advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, following the SPOTLIGHT and GLOW Phase 3 trials, which established zolbetuximab plus fluoropyrimidine-platinum chemotherapy as a first-line option for patients with CLDN18.2-positive, HER2-negative disease...Collectively, current evidence supports a reassessment-based rather than assumption-based approach to CLDN18.2 sequencing. However, key gaps remain, including the optimal interface with PD-1-based first-line therapy, the geographic generalizability of several next-generation datasets, standardized retesting strategies at progression, and prospective validation of modality-specific sequencing after target modulation.

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

P2/3, N=126, Not yet recruiting, AstraZeneca AB

Background: Claudin 18.2 (CLDN18.2) has become a clinically relevant therapeutic target in gastric adenocarcinoma (GC), with zolbetuximab now approved for use in CLDN18.2-positive, HER2-negative advanced disease... CLDN18.2 shows excellent intratumoral reproducibility and a stable biological profile in GC, supporting its diagnostic reliability in biopsies and value as a predictive biomarker. A subset with extreme expression demonstrated aggressive features, suggesting a potential "claudin-driven" phenotype requiring further study.

P2, N=90, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

Overall, these findings support the recognition of GBASC as a distinct molecular entity potentially requiring dedicated therapeutic strategies.

P3, N=592, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting