CLDN18.2 expression

P1, N=17, Completed, Turning Point Therapeutics, Inc. | Active, not recruiting --> Completed | N=42 --> 17

Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.

P2, N=25, Not yet recruiting, Harbin Medical University

CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

Data suggested CLDN18.2 expression levels were independent of PD-L1 status, and support the use of Transcenta 14G11 antibody for CLDN18.2 detection regardless of sample collection methods, location, and patient demographics. An anti-CLDN18.2 companion diagnostic device based on 14G11 is being developed (CLDN18.2 IHC 14G11 pharmDx, Agilent Technologies, Inc.).

P1/2, N=114, Recruiting, Phanes Therapeutics | N=72 --> 114

Among them, trastuzumab, as the first targeted drug for gastric cancer, effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed HER2, and has become the standard treatment for HER2-positive gastric cancer patients. Ramucirumab, on the other hand, inhibits tumor angiogenesis by targeting VEGFR2 and has been used as second-line therapy for advanced gastric cancer patients. In addition, bemarituzumab targets overexpressed FGFR2, while zolbetuximab targets overexpressed CLDN18.2, significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials. This article reviews the roles of tumor driver genes in the progression of gastric cancer; and the treatment strategies for gastric cancer based on targeting HER2, VEGF, FGFR2, CLDN18.2, MET and other tumor driver genes, aiming to provide reference for clinical application of targeted therapy for gastric cancer.

CLDN18.2+ expression is associated with early stage GACs, but with metastatic disease in E/GEJACs. CLDN18.2+ expression is not affected by preoperative treatment or HER2 status. These findings expand our recognition of subsets of patients who may benefit from targeted CLDN18.2 therapy.

Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further...Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.

P1/2, N=72, Recruiting, Phanes Therapeutics | Phase classification: P1 --> P1/2 | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Nov 2023 --> Dec 2025

These results indicate that radionuclide-labeled scFv-Fc molecular probes ([I]I-SF106 and [Lu]Lu-DOTA-SF106) provide a new possibility for the diagnosis and treatment of CLDN18.2-positive cancer patients in clinical practice.

P2, N=123, Recruiting, AstraZeneca

Our findings illuminated the role of the CLDN18.2-mediated interaction between cancer cells and CAFs in promoting gastric cancer progression and embolism, thereby providing insight into potential therapeutic avenues for CLDN18.2 positive cancers. Video Abstract.

P1, N=96, Recruiting, Peking University | Not yet recruiting --> Recruiting

P1, N=320, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Phase classification: P1a/1b --> P1 | Trial completion date: Apr 2024 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

The Ga-DOTA-T37 probe exhibits good in vitro properties and high stability as a hydrophilic probe; it has high biological safety, and positron emission tomography/computed tomography (PET/CT) studies have shown that it can specifically target CLDN18.2 protein and CLDN18.2-positive tumors in mice. Ga-DOTA-T37 demonstrated the superiority and feasibility of using a CLDN18.2-specific probe in PCT/CT imaging, which deserves further development and exploitation.

In preclinical studies, [Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.

41, 2023. Clinical trial information: NCT05980416.

No data analysis is available as of the submission deadline. Clinical trial information: NCT05862324.

These data support clinical development of the CLDN18.2-307-mAb and CLDN18.2-307-ADC for treatment of CLDN18.2+ cancers. Both are now being investigated in phase 1 clinical studies.

P1/2, N=269, Suspended, Sotio Biotech Inc. | Recruiting --> Suspended

P2, N=25, Not yet recruiting, First Affiliated Hospital of Anhui Medical University

P2, N=143, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Jul 2024 --> Dec 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

IMAB362/Zolbetuximab, a first-in-class IgG1 antibody directed against the cancer-associated gastric-lineage marker CLDN18.2, has recently been reported to have met its primary endpoint in two phase 3 trials as a first-line treatment in combination with standard of care chemotherapy in CLDN18.2-positive Her2 negative advanced gastric cancer. BNT141 administration did not perpetrate mortality, clinical signs of toxicity, or gastric pathology in animal studies. A phase 1/2 clinical trial with BNT141 mRNA-LNP has been initiated in advanced CLDN18.2-expressing solid cancers (NCT04683939).

P1/2, N=13, Terminated, BioNTech SE | N=96 --> 13 | Trial completion date: Sep 2024 --> Jul 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Jul 2023; Sponsor decision

P1, N=42, Active, not recruiting, Turning Point Therapeutics, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P1 | Trial completion date: Aug 2024 --> Jan 2024 | Trial primary completion date: Aug 2024 --> Jan 2024

OV-BiTE further reprogrammed macrophages to a more pro-inflammatory antitumor state, and OV-BiTE-induced macrophages exhibited greater cytotoxicity on the co-cultured tumor cell. This dual cytotoxic and immunomodulatory approach warrants further development for pancreatic cancer before clinical investigation.

P1, N=60, Recruiting, Shijiazhuang Yiling Pharmaceutical Co. Ltd

P3, N=566, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Jan 2025 --> May 2025

P1/2, N=200, Recruiting, AstraZeneca

CLDN18.2 is expressed at a low level in tumour tissues and serves as an independent prognostic factor for patients with GC. Furthermore, CLDN18.2 correlates with immune infiltrating cells and PD-L1 expression.

P1, N=120, Recruiting, Elevation Oncology | Not yet recruiting --> Recruiting

The expression of Cldn18.2 was closely related to gastric-type GC, so gastric-type GC patients may benefit more from targeted drugs targeting Cldn18.2. In GC cells, depletion of Cldn18.2 may influence cell cycle and immune response by affecting Wnt signaling pathway and PD 1 pathway.

We further demonstrated that recurrent tumors following H9 CAR-IL15 T-cell therapy downregulated CLDN18.2 expression, suggesting immune escape through the selection of antigen-negative cells under persistent CAR-T-cell immune pressure. In conclusion, our findings provide preclinical evidence supporting the clinical evaluation of IL-15-expressing CLDN18.2 CAR-T cells in patients with CLDN18.2-positive tumors.

P1, N=120, Not yet recruiting, Elevation Oncology

P1, N=96, Not yet recruiting, Peking University

P2, N=8, Completed, Shanghai Zhongshan Hospital | Recruiting --> Completed | N=40 --> 8 | Trial completion date: Jul 2024 --> May 2023

The PK profile, s4-1BB induction, and efficacy signal support 12 mg/kg as an optimal dose. Further development of givastomig mono- and combo- therapy in GEC and other cancers is planned.

Encouraging anti-tumor activities have been observed regardless of the CLDN18.2 expression levels, including expression as low as ≥10% tumor cells staining ≥1+, <40% tumor cells staining <2+ or 3+. Overall survival data will be presented.

Background Zolbetuximab showed efficacy for gastric cancer with Claudin (CLDN)18.2 expression...Conclusions CLDN18.2 expression was observed in 38% of resected gastric cancer samples, which was consistent with previous reports. CLDN18.2 expression was not related to prognosis and specific relationship was not observed in clinical/molecular characteristics of resected gastric cancer.