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

Abstract Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222). Patients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV). Oxaliplatin was given for 8-12 cycles; other agents were continued until disease progression, unacceptable toxicity, or death. The primary endpoint was progression-free survival (PFS) in the intent-to-treat (ITT) and MET immunohistochemistry (IHC) expression-positive populations. Between September 2011 and November 2012, 194 patients were enrolled. In September 2013, an interim analysis recommended stopping onartuzumab treatment due to lack of efficacy. At the time of the final analysis in February 2014, no significant improvement in PFS was seen with onartuzumab versus placebo in either the ITT or MET IHC-positive populations. An improvement in PFS was noted in the MET IHC-negative population. Neither overall survival nor response rate was improved with onartuzumab. The incidence of fatigue, peripheral edema, and deep vein thrombosis was increased with onartuzumab relative to placebo.