CLDN18 (Claudin 18)

P2, N=100, Recruiting, Jeeyun Lee | N=50 --> 100

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.

In vivo studies indicated that dual targeting of TIGIT and Claudin 18.2 (CLDN18.2) inhibited PMGC progression and ascites formation. These findings indicate that CLDN18.2 and TIGIT are potential therapeutic targets, whose combined inhibition suppresses PMGC progression and ascites formation, providing valuable insights for PMGC treatment.

P3, N=600, Recruiting, NingBo Junyan Hongshi Biosciences Co., Ltd | Not yet recruiting --> Recruiting

P3, N=570, Not yet recruiting, Astellas Pharma Global Development, Inc.

h1D6 was generated by immunizing CLDN18.2 knockout mice followed by humanization; it exhibited high specificity for CLDN18.2 (no cross-reactivity with CLDN18.1) and improved binding affinity and in vivo efficacy vs. existing antibodies (e.g., IMAB362)...In vivo, 89Zr-labeled h1D6-ADC-5 showed prolonged tumor accumulation in CLDN18.2-positive xenograft, with significant tumor regression (nearly complete regression at 10 mg/kg) while no overt toxicity was observed based on body weight and histology. These preclinical data demonstrate that h1D6-ADC-5 is a promising candidate for treating CLDN18.2-positive cancers.

Zolbetuximab, a CLDN18.2-targeted monoclonal antibody, has been approved in combination with chemotherapy as a first-line treatment option for patients with HER2-negative and CLDN18.2-positive gastric adenocarcinoma...In conclusion, precision targeting of CLDN18.2 represents a promising approach in GC therapy, shifting from conventional chemotherapy to biomarker-guided strategies. Continued development of next-generation agents and rational combination therapies may enhance outcomes and expand benefit.

As FGFR2b-directed strategies move forward, their success will depend not only on drug efficacy, but also on standardized testing, careful reporting, and selective reassessment when disease biology changes. FGFR2b therefore offers a useful model for how protein biomarkers can be developed in gastric cancer: not as isolated positive-or-negative labels, but as clinically interpreted variables within a changing therapeutic landscape.

This review suggests that Claudin18.2 may serve as a key regulator of immune dysfunction rather than immune exclusion in gastric cancer, providing a potential biological rationale for combinatorial strategies integrating Claudin18.2-targeted therapies with immune checkpoint inhibition. Given the heterogeneity of available studies and the indirect nature of some evidence, these insights should be interpreted as exploratory; they may nonetheless help guide patient stratification and inform the rational design of future combination immunotherapy trials in Claudin18.2-positive gastric cancer.

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