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Role of MetMAb (OA-5D5) in c-MET active lung malignancies
Mosmi Surati1, Premal Patel, Amy Peterson
1University of Chicago, Pritzker School of Medicine, Chicago, IL 60637, USA.
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.
Insights
MetMAb (OA-5D5) shows promise in treating MET-driven cancers like NSCLC, improving survival in Phase II trials. This monoclonal antibody is well-tolerated and undergoing Phase III validation for targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The c-MET receptor tyrosine kinase and its ligand HGF are implicated in various cancers.
- MetMAb (OA-5D5) is a novel monoclonal antibody targeting the c-MET pathway.
- Dysregulation of c-MET signaling drives tumor growth and progression in certain malignancies.
Purpose of the Study:
- To review the structure and function of the c-MET/HGF signaling axis.
- To provide an overview of targeted therapies interfering with MET-HGF signaling.
- To discuss preclinical and clinical data for MetMAb and offer expert opinion.
Main Methods:
- Literature review of c-MET pathway and MetMAb.
- Analysis of preclinical studies investigating MetMAb.
- Evaluation of clinical trial data, including Phase II results in NSCLC.
Main Results:
- MetMAb demonstrates inhibition of c-MET receptor tyrosine kinase.
- Phase II trials in NSCLC suggest improved overall survival in MET-diagnostic-positive patients.
- MetMAb has shown good tolerability as monotherapy and in combination regimens.
Conclusions:
- MetMAb is well-tolerated and may improve survival in advanced NSCLC patients with c-MET-driven disease.
- Combination therapy with erlotinib is being investigated.
- Phase III studies are ongoing to validate efficacy and identify optimal patient populations for MetMAb treatment.
