Purpose Bevacizumab regimens are approved for the treatment of recurrent 
glioblastoma in many countries. Aberrant mesenchymal-epithelial transition 
factor (MET) expression has been reported in glioblastoma and may contribute to 
bevacizumab resistance. The phase II study GO27819 investigated the monovalent 
MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus 
bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence 
after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly 
assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once 
every 3 weeks) or Pla + Bev until disease progression. The primary end point was 
progression-free survival by response assessment in neuro-oncology criteria. 
Secondary end points were overall survival, objective response rate, duration of 
response, and safety. Exploratory biomarker analyses correlated efficacy with 
expression levels of MET ligand hepatocyte growth factor, O6-methylguanine-DNA 
methyltransferase promoter methylation, and glioblastoma subtype. Results Among 
129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline 
characteristics were balanced. The median progression-free survival was 3.9 
months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% 
CI, 0.72 to 1.56; P = .7444). The median overall survival was 8.8 months for Ona 
+ Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37; P 
= .1389). Grade ≥ 3 adverse events were reported in 38.5% of patients who 
received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory 
biomarker analyses suggested that patients with high expression of hepatocyte 
growth factor or unmethylated O6-methylguanine-DNA methyltransferase may benefit 
from Ona + Bev. Conclusion There was no evidence of further clinical benefit 
with the addition of onartuzumab to bevacizumab compared with bevacizumab plus 
placebo in unselected patients with recurrent glioblastoma in this phase II 
study; however, further investigation into biomarker subgroups is warranted.