onartuzumab   

GtoPdb Ligand ID: 8966

Synonyms: MetMAb | OA-5D5 | OA5D5 | PRO 143966
Compound class: Antibody
Comment: Onartuzumab is an investigational, humanized monoclonal antibody targeting the MET receptor tyrosine kinase, a proto-oncogene which acts as a hepatocyte growth factor receptor. The protein is a monovalent (single-armed) construct, as opposed to bi-valent intact antibody structures.
Peptide sequence information for this antibody is available from its IMGT/mAb-DB record.
BLAST peptide analysis reveals identical match with sequences deposited with patent US7615529 [4], which relate to the monoclonal isolated from hybridoma 5D5.11.6 therein.
No information available.
Summary of Clinical Use
In early 2014, a phase III study of onartuzumab (in combination with erlotinib; NCT01456325) in patients with MET-positive non-small cell lung cancer was terminated due to a lack of clinically meaningful efficacy [1,7]. Additional Phase III studies evaluating onartuzumab's antineoplastic activity in MET-positive lung, gastric and other solid cancers are ongoing [6]. Click here to link to ClinicalTrials.gov's list of Phase III onartuzumab trials.
Mechanism Of Action and Pharmacodynamic Effects
MET proteins dimerise upon hepatocyte growth factor (HGF) binding. This triggers a signalling cascade that promotes cell growth, division and migration. Activation of the MET pathway has been proposed as a mechanism of tumour growth and metastasis [3,5].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01456325 A Study of Onartuzumab (MetMAb) in Combination With Tarceva (Erlotinib) in Participants With Met Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Chemotherapy For Advanced or Metastatic Disease (MetLung) Phase 3 Interventional Genentech, Inc.