|
Synonyms: claudiximab | GC-182 | IMAB-362 | IMAB362
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 [4,8]. 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 [1-3]. 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) [9], esophageal, ovarian, and lung tumours [4]. Zolbetuximab binds to the first extracellular N-terminal domain which is unique to the CLDN18.2 splice variant [4,9].
|
| No information available. |
Summary of Clinical Use  |
| Zolbetuximab (IMAB362) has progressed to clinical evaluation (max phase 3) for advanced, claudin 18.2-positive gastric and gastroesophageal cancers. In November 2010 the EMA granted orphan drug (OD) designation as a treatment for claudin 18.2-positive gastric cancers, and FDA OD was issued in September 2013 for pancreatic cancers. |
| 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 | 5 | |
| 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 | 7 | |
| 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] | 6 |
