BACKGROUND: Onartuzumab is a monovalent monoclonal antibody that binds with the 
extracellular domain of the MET receptor. Given the role of MET in 
non-small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to 
first-line chemotherapy efficacy in non-squamous NSCLC.
METHODS: Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by 
MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg 
intravenously every 3 weeks) or placebo in combination with either 
paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with 
platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or 
pemetrexed and onartuzumab/placebo as appropriate. Co-primary endpoints of this 
phase II study were progression-free survival (PFS) in all patients and in MET+ 
patients (2+/3+), defined by the Ventana immunohistochemistry assay; secondary 
endpoints included overall survival (OS), objective response rate (ORR), safety, 
and pharmacokinetics.
RESULTS: Efficacy data were available for 139 and 120 patients in the 
bevacizumab and pemetrexed cohorts, respectively. No benefit was seen in the PFS 
endpoint in the intent-to treat population of either cohort, but was numerically 
worse in the onartuzumab arm of the MET+ subgroup of the bevacizumab cohort. The 
onartuzumab and placebo arms had similar ORR and OS results in both cohorts. A 
higher incidence of some adverse events was observed with onartuzumab versus 
placebo, including peripheral edema (30% vs. 3%, bevacizumab cohort; 48% vs. 
14%, pemetrexed cohort) and venous thromboembolic events (bevacizumab cohort 
only, 15% vs. 6%).
CONCLUSION: Onartuzumab does not appear to provide any additional clinical 
benefit when given in combination with current first-line standard-of-care 
chemotherapy for non-squamous NSCLC.