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Synonyms: claudiximab | GC-182 | IMAB-362 | IMAB362 | Vyloy® | zolbetuximab-clzb
zolbetuximab is an approved drug (Japan PMDA, EMA & FDA (2024))
Compound class:
Antibody
Comment: Zolbetuximab (IMAB362) is an investigational, first-in-class monoclonal antibody targeting the cell surface molecule claudin18.2 (CLDN18.2), a pan-cancer drug target [5,9]. Claudin-18 is a tight-junction protein. Splice variant 2 is reported to be a highly selective cell lineage marker of gastric mucosal cells, and it is an active molecular target for tumour-targeted immunotherapy [1-2,4]. CLDN18.2 is retained on malignant transformation and is expressed in a significant proportion of primary gastric cancers and their metastases, and ectopic expression of CLDN18.2 is identified in distinct histologic subtypes of pancreatic (primary tumour and metastases) [10], esophageal, ovarian, and lung tumours [5]. Zolbetuximab binds to the first extracellular N-terminal domain which is unique to the CLDN18.2 splice variant [5,10].
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| No information available. |
Summary of Clinical Use  |
| Zolbetuximab (IMAB362) was progressed to clinical evaluation for advanced, claudin 18.2+ve gastric and gastroesophageal cancers. In November 2010 the EMA granted orphan drug (OD) designation as a treatment for claudin 18.2+ve gastric cancers, and FDA OD was issued in September 2013 for pancreatic cancers. First approval was granted in Japan in March 2024, for the treament of HER2-ve, CLDN18.2+ve unresectable, advanced/recurrent gastric cancer (including gastroesophageal junction tumours) [3]. EMA approval for this indication followed in September 2024, and FDA approval was granted in October 2024. |
| Mechanism Of Action and Pharmacodynamic Effects |
| IMAB362 inhibits tumour growth and kills cancer cells by indirect (complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity) and direct (antiproliferative and proapoptotic) mechanisms. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT01630083 | Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer | Phase 2 Interventional | Astellas Pharma Inc | 6 | |
| NCT03816163 | A Study to Assess the Efficacy and Safety of IMAB362 in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma | Phase 2 Interventional | Astellas Pharma Inc | ||
| NCT03505320 | A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab (IMAB362) in Participants With Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma | Phase 2 Interventional | Astellas Pharma Inc | ||
| NCT01197885 | Efficacy and Safety Study of Multiple Doses of IMAB362 in Patients With Advanced Gastroesophageal Cancer | Phase 2 Interventional | Astellas Pharma Inc | 8 | |
| NCT03504397 | A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer | Phase 3 Interventional | Astellas Pharma Inc | Zolbetuximab treament significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 (compared to placebo + mFOLFOX6) in patients with previously untreated CLDN18.2+ve, HER2-ve, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. [mFOLFOX6 = modified folinic acid [or levofolinate], fluorouracil, and oxaliplatin regimen] | 7 |
| External links |
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For extended ADME data see the following: European Medicines Agency (EMA) |
