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BIOMARKER:

CLDN18.2 expression

i
Other names: CLDN18, Claudin-18, Surfactant, Pulmonary Associated Protein J, Surfactant Associated 5, SFTA5, SFTPJ
Entrez ID:
Related biomarkers:
1m
State of the art and upcoming trends in claudin-directed therapies in gastrointestinal malignancies. (PubMed, Curr Opin Oncol)
CLDN18.2 will be an important target in GAC. Early understanding of how to target CLDN18.2 based on the level of expression (high, moderate, low) will be the key to success in this area. Studying these as separate entities should be considered. Resistance patterns, loss of CLDN18.2 expression, role in the refractory setting, and if any role in localized disease are questions that remain. Other targets for claudin that target claudin six and four are under investigation. Their role in GI malignancies will soon be further clarified.
Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive
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oxaliplatin • Vyloy (zolbetuximab)
2ms
Enrollment closed • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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gemcitabine • albumin-bound paclitaxel • Vyloy (zolbetuximab)
2ms
Study of Turning Point Therapeutics LM-302 in Patients With Advance Solid Tumors (clinicaltrials.gov)
P1, N=17, Completed, Turning Point Therapeutics, Inc. | Active, not recruiting --> Completed | N=42 --> 17
Trial completion • Enrollment change • Metastases
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MSI (Microsatellite instability) • CLDN18 (Claudin 18)
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MSI-H/dMMR • CLDN18.2 expression • CLDN18.2 positive
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BMS-986476
2ms
68Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients. (PubMed, J Nucl Med)
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.
Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive
2ms
DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy. (PubMed, Cancer Immunol Immunother)
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.
Journal • Trispecific
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CLDN18 (Claudin 18) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • CRP (C-reactive protein)
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CLDN18.2 expression
3ms
New P2 trial • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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Tyvyt (sintilimab) • IBI-343
3ms
Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer: A retrospective study. (PubMed, Chin J Cancer Res)
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.
Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
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PD-L1 expression • HER-2 expression • CLDN18.2 expression • CLDN18.2 positive • HER-2 positive + PD-L1 expression • CLDN1 positive • PD-L1 expression + HER-2 expression
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satricabtagene autoleucel (CT041)
3ms
Prevalence of claudin18.2 expression in gastric/gastroesophageal junction adenocarcinoma among patients in TranStar101 and TranStar102 clinical trials (AACR 2024)
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.).
Clinical • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic • IO Companion diagnostic
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PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
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PD-L1 expression • CLDN18.2 expression • CLDN18.2 positive • CLDN1 positive
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PD-L1 IHC 28-8 pharmDx
4ms
Enrollment change
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CLDN18 (Claudin 18)
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HER-2 overexpression • CLDN18.2 expression
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Keytruda (pembrolizumab) • gemcitabine • 5-fluorouracil • capecitabine • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • PT886
4ms
Advances in targeted therapy for gastric cancer based on tumor driver genes. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban)
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.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2) • CLDN18 (Claudin 18) • KDR (Kinase insert domain receptor)
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HER-2 positive • HER-2 overexpression • CLDN18.2 expression • FGFR2 overexpression • CLDN18.2 overexpression • CLDN1 overexpression
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Herceptin (trastuzumab) • Cyramza (ramucirumab) • Vyloy (zolbetuximab) • bemarituzumab (AMG 552)
4ms
Clinicopathologic Characterization of Claudin 18.2 Expression in Surgically-Resected Gastric and Esophageal Adenocarcinomas (USCAP 2024)
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.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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HER-2 positive • HER-2 negative • HER-2 expression • CLDN18.2 expression • CLDN18.2 positive • CLDN1 positive
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PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • VENTANA anti-MLH-1 (M1) Mouse Monoclonal Primary Antibody • VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody • VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody • VENTANA anti-PMS2 (A16-4) Mouse Monoclonal Primary Antibody
4ms
Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes. (PubMed, Virchows Arch)
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.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
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HER-2 negative • CLDN18.2 expression • CLDN18.2 positive
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Vyloy (zolbetuximab)
5ms
PT886 For Treatment of Patients With Metastatic/Advanced Gastric, Gastroesophageal Junction and Pancreatic Adenocarcinoma (the TWINPEAK Study) (clinicaltrials.gov)
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
Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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HER-2 overexpression • CLDN18.2 expression
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gemcitabine • albumin-bound paclitaxel • PT886
5ms
Exploration of radionuclide labeling of a novel scFv-Fc fusion protein targeting CLDN18.2 for tumor diagnosis and treatment. (PubMed, Eur J Med Chem)
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.
Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive
5ms
New P2 trial • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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gemcitabine • 5-fluorouracil • leucovorin calcium • AZD0901 • Onivyde (nanoliposomal irinotecan)
5ms
Claudin-18.2 mediated interaction of gastric Cancer cells and Cancer-associated fibroblasts drives tumor progression. (PubMed, Cell Commun Signal)
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.
Journal
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CLDN18 (Claudin 18) • S100A4 (S100 calcium binding protein A4)
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CLDN18.2 expression • CLDN18.2 positive • CLDN18.2 overexpression • CLDN18.2 underexpression
6ms
Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors (clinicaltrials.gov)
P1, N=96, Recruiting, Peking University | Not yet recruiting --> Recruiting
Enrollment open • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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AZD6422
6ms
Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, in Patients With Advanced Malignancies (clinicaltrials.gov)
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
Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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Tyvyt (sintilimab) • IBI-389
6ms
Screening, Construction, and Preliminary Evaluation of CLDN18.2-Specific Peptides for Noninvasive Molecular Imaging. (PubMed, ACS Pharmacol Transl Sci)
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.
Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive • CLDN18.2 overexpression
6ms
[Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models. (PubMed, Eur J Nucl Med Mol Imaging)
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.
Preclinical • Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive • CLDN18.2 overexpression • CLDN1 overexpression
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osemitamab (TST001)
6ms
First-in-human phase 1/2 trial evaluating TAC01-CLDN18.2 autologous T cells in CLDN18.2-positive solid tumors. (ASCO-GI 2024)
No data analysis is available as of the submission deadline. Clinical trial information: NCT05862324.
P1/2 data • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
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HER-2 negative • CLDN18.2 expression • CLDN18.2 positive • CLDN18 fusion
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TAC101-Claudin18.2
6ms
Clinical • P1 data
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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EO-3021
7ms
Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody-drug Conjugate for Treatment of CLDN18.2 Positive Cancers. (PubMed, Mol Cancer Ther)
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.
Journal
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive • CLDN1 positive
7ms
Trial suspension • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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HER-2 overexpression • HER-2 negative • CLDN18.2 expression
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SOT102
7ms
New P2 trial • Combination therapy • Metastases
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PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
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PD-L1 expression • CLDN18.2 expression • CLDN18.2 positive
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Tyvyt (sintilimab) • IBI-343
8ms
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
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PD-L1 expression • HER-2 negative • CLDN18.2 expression • CLDN18.2 positive
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • 5-fluorouracil • oxaliplatin • leucovorin calcium • Vyloy (zolbetuximab)
8ms
Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody. (PubMed, Oncoimmunology)
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).
Preclinical • Journal
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
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HER-2 positive • HER-2 negative • CLDN18.2 expression • CLDN18.2 positive
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Vyloy (zolbetuximab) • BNT141
9ms
Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141 in Patients With Unresectable or Metastatic CLDN18.2-positive Gastric, Pancreatic, Ovarian and Biliary Tract Tumors (clinicaltrials.gov)
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
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive
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gemcitabine • albumin-bound paclitaxel • BNT141
9ms
Study of Turning Point Therapeutics LM-302 in Patients With Advance Solid Tumors (clinicaltrials.gov)
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
Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Metastases
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MSI (Microsatellite instability) • CLDN18 (Claudin 18)
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MSI-H/dMMR • CLDN18.2 expression • CLDN18.2 positive
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BMS-986476
9ms
Claudin18.2 bispecific T cell engager armed oncolytic virus enhances antitumor effects against pancreatic cancer. (PubMed, Mol Ther Oncolytics)
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.
Journal • Oncolytic virus • IO biomarker
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CLDN18 (Claudin 18) • CD4 (CD4 Molecule)
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CLDN18.2 expression
9ms
A Study of Bio-008 in Subjects With Advanced or Metastatic Solid Tumours (clinicaltrials.gov)
P1, N=60, Recruiting, Shijiazhuang Yiling Pharmaceutical Co. Ltd
New P1 trial • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive
10ms
Trial completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
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HER-2 negative • CLDN18.2 expression
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5-fluorouracil • oxaliplatin • leucovorin calcium • Vyloy (zolbetuximab)
10ms
New P1/2 trial • Metastases
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CLDN18 (Claudin 18)
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CLDN18.2 expression • CLDN18.2 positive • CLDN1 positive
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AZD5863
10ms
CLDN18.2 expression and its impact on prognosis and the immune microenvironment in gastric cancer. (PubMed, BMC Gastroenterol)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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PD-L1 expression • HER-2 expression • CLDN18.2 expression • CLDN18.2 positive
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Vyloy (zolbetuximab)
10ms
Study of EO-3021 in Adult Patients With Solid Tumors Likely to Express CLDN18.2 (clinicaltrials.gov)
P1, N=120, Recruiting, Elevation Oncology | Not yet recruiting --> Recruiting
Enrollment open
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CLDN18 (Claudin 18)
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CLDN18.2 expression
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EO-3021
10ms
Correlation of Claudin18.2 expression with clinicopathological characteristics and prognosis in gastric cancer. (PubMed, Pathol Res Pract)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
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CLDN18.2 expression • MUC5AC expression
10ms
IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models. (PubMed, Front Immunol)
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.
Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
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CLDN18 (Claudin 18) • IL15 (Interleukin 15)
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CLDN18.2 expression • CLDN18.2 positive
10ms
Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors (clinicaltrials.gov)
P1, N=96, Not yet recruiting, Peking University
New P1 trial • Metastases
|
CLDN18 (Claudin 18)
|
CLDN18.2 expression
|
AZD6422
10ms
New P1 trial
|
CLDN18 (Claudin 18)
|
CLDN18.2 expression
|
EO-3021
11ms
TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer (clinicaltrials.gov)
P2, N=8, Completed, Shanghai Zhongshan Hospital | Recruiting --> Completed | N=40 --> 8 | Trial completion date: Jul 2024 --> May 2023
Trial completion • Enrollment change • Trial completion date • Metastases
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CLDN18 (Claudin 18)
|
CLDN18.2 expression
|
osemitamab (TST001)
11ms
Claudin 18.2 expression in resected gastric cancer (ESMO 2023)
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.
PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
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HER-2 positive • MSI-H/dMMR • CLDN18.2 expression
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PD-L1 IHC 28-8 pharmDx • VENTANA CLDN18 (43-14A) Assay
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Vyloy (zolbetuximab)