BACKGROUND: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway is 
associated with poor prognosis, more aggressive biological characteristics of 
the tumor, and shortened survival in patients with metastatic colorectal cancer 
(mCRC). Onartuzumab (MetMAb) is a recombinant humanized monovalent monoclonal 
antibody directed against MET. We present the treatment rationale and protocol 
for an ongoing randomized multicenter placebo-controlled phase II study designed 
to evaluate the efficacy and safety of MetMAb combined with bevacizumab and 
mFOLFOX-6 (5-fluoruracil, leucovorin, and oxaliplatin).
PATIENTS AND METHODS: Eligible patients with previously untreated mCRC are 
randomized 1:1 to either mFOLFOX-6 combined with bevacizumab and placebo 
followed by 5-fluorouracil/leucovorin plus bevacizumab and placebo or mFOLFOX6, 
bevacizumab plus MetMAb followed by 5 FU/LV, bevacizumab, and MetMAb. The 
primary end point of this study is progression-free survival (PFS) in the 
intent-to-treat (ITT) population. Secondary end points include overall survival 
(OS), objective response rate, and safety. Subanalyses will be performed to 
evaluate the effect of MET receptor expression on study primary and secondary 
end points. Correlative studies will be performed on tissue- and blood-derived 
biomarkers related to both HGF/MET signaling and other associated pathway 
markers.