Role of MetMAb (OA-5D5) in c-MET active lung malignancies

Expert Opin Biol Ther. 2011 Dec;11(12):1655-62. doi: 10.1517/14712598.2011.626762.

Abstract

Introduction: MetMAb (OA-5D5) is a one-armed monoclonal antibody developed to bind to and inhibit c-MET receptor tyrosine kinase. Though only in early clinical testing, this agent holds great promise in diseases thought to be driven by c-MET activation, as evidenced by the Phase II results in NSCLC where a benefit in overall survival was observed in patients with MET-diagnostic-positive disease. Thus far, both alone and in combination with other targeted agents, this drug has been well tolerated and no new significant safety signals have been identified.

Areas covered: This review summarizes the structure and function of the c-MET receptor and its ligand hepatic growth factor (HGF), provides an overview of select targeted monotherapies developed to interfere in the MET-HGF signaling pathway, discusses pre-clinical and clinical data surrounding MetMAb, and concludes with an expert opinion regarding this novel agent.

Expert opinion: MetMAb has been well tolerated and based on Phase II data testing it, in combination with erlotinib in advanced NSCLC, may have a role in improving survival in patients with disease driven by c-MET activation. However, Phase III validation is underway and the results of these studies will help elucidate which patients will benefit most from this novel agent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Ligands
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / immunology
  • Proto-Oncogene Proteins c-met / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ligands
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met