Onartuzumab

Onartuzumab is a humanized monovalent monoclonal antibody directed against the hepatocyte growth factor receptor (c-Met) with potential antineoplastic activity

Onartuzumab binds to the extracellular domain of c-Met and thus prevents the ligand from binding. This inhibits the activation of the c-Met signalling pathway. This leads to cell death in c-Met-expressing tumor cells.

c-Met is a transmembrane receptor tyrosine kinase that is overexpressed on the cell surfaces of a large number of tumor cells. C-Met activates the hepatocyte growth factor (HGF) through its ligand and plays a role in embryonic development and wound healing. Aberrant MET signals can be triggered by autocrine production of HGF, overexpression of MET and amplification of MET. This results in an oncogenic situation which plays a role in several human malignant diseases.

Advanced non-small cell lung cancer; solid gastrointestinal carcinoma.

An approval of the preparation is still pending.

1. Bendell JC et al (2017) A Phase II Randomized Trial (GO27827) of First-Line FOLFOX Plus Bevacizumab with or Without the MET Inhibitor Onartuzumab in Patients with Metastatic Colorectal Cancer. Oncologist 22:264-271.
2. Nishio M et al (2015) Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors and MET-positive lung cancer. Invest New Drugs 33:632-640.
3. Rolfo C et al (2015) Onartuzumab in lung cancer: the fall of Icarus? Expert Rev Anticancer Ther 15:487-489.
4. Sano Y et al (2015) Combining onartuzumab with erlotinib inhibits growth of non-small cell lung cancer with activating EGFR mutations and HGF overexpression. Mol Cancer Ther 14:533-541.
5. Shah MA et al (2017) Effect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET- Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial. JAMA Oncol 3:620-627.