zolbetuximab   Click here for help

GtoPdb Ligand ID: 9209

Synonyms: claudiximab | GC-182 | IMAB-362 | IMAB362 | VYLOY® (Japan)
Approved drug
zolbetuximab is an approved drug (Japan (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].
No information available.
Summary of Clinical Use Click here for help
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]. Zolbetuximab is under regulatory review in jurisdictions including the US, China, Australia and the EU.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
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