CLDN18.2 positive

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

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.

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

A 59-year-old man with CLDN18.2-positive stage IV gastric cancer and suspected peritoneal dissemination received zolbetuximab with capecitabine and oxaliplatin. This case suggests that zolbetuximab-based chemotherapy may enable conversion surgery in selected patients. Careful perioperative management is essential, and further studies are needed.

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.

We further discuss emerging triplet strategies and next-generation CLDN18.2-targeted platforms. Rather than considering CLDN18.2 as an isolated biomarker, we propose a treatment-oriented framework for integrating zolbetuximab into contemporary first-line management of HER2-negative advanced gastric cancer.

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