Clinical Trial Profiles: MetMAb and ARQ 197 in Non–Small Cell Lung Cancer
Published Online: Thursday, June 21, 2012
David Spigel, MD
Both MetMAb (onartuzumab; Genentech), a monoclonal antibody, and ARQ 197 (tivantinib; ArQule and Daiichi Sankyo), a small-molecule inhibitor, are targeted therapies that block signaling pathways in cancer cells. Specifically, they inhibit c-MET, a cell membrane receptor molecule implicated in both tumor progression and metastasis in several cancers, including NSCLC.
“It’s an oncogenic pathway that drives cancer growth. The goal is to shut this pathway down,” said David Spigel, MD, director of Lung Cancer Research at the Sarah Cannon Research Institute in Nashville, Tennessee, and the principal investigator for the MetMAb trial.
The drugs, which are being tested in late-stage patients who have already received one or two lines of standard therapy, represent a paradigm shift in lung cancer treatment. (Related: MET Inhibitors in Cancer Therapy)
Alan Sandler, MD
In each trial, the drugs are being tested in combination with another targeted cancer treatment, erlotinib (Tarceva; Genentech). Erlotinib is a receptor tyrosine kinase inhibitor that blocks the signaling pathway of the epidermal growth factor receptor (EGFR), a cell surface receptor implicated in cancer cell growth. MET has been implicated in part in erlotinib resistance.
Reinhard von Roemeling, MD
“Each drug has anticancer properties, and when we combine them there may be at least additive activity. It’s not clear how additive, although there appears to be a benefit in preclinical models,” Spigel noted of the MetMAb/erlotinib combination.
MetMAb TrialMetMAb is being tested in a randomized, double-blind, phase III study that will assign nearly 500 patients who have already been treated with standard chemotherapy for advanced or metastatic disease into two groups. One group will take MetMAb in combination with erlotinib. The other group will take erlotinib with a placebo.
The study, which began in January 2012, has an estimated completion date of December 2015. The primary outcome measure is overall survival, while secondary endpoints are progression-free survival, overall response rate, and safety.
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