The objective of this study was to evaluate circulating hepatocyte growth factor 
(cHGF) as a pharmacodynamic biomarker of Met inhibition for onartuzumab (MetMAb, 
OA5D5v2) in a phase I trial in patients with advanced cancers and a phase II 
trial in non-small cell lung cancer (NSCLC). The phase I study was a dose 
escalation trial with onartuzumab administered i.v. once every three weeks. The 
phase II study was a randomized two-arm trial in which onartuzumab or placebo 
was administered in combination with erlotinib in 137 patients with second and 
third line (2/3L) NSCLC. cHGF levels were evaluated by ELISA at multiple time 
points over the treatment period. Onartuzumab administration resulted in an 
acute and sustained rise in cHGF in both the phase I and phase II studies. 
Elevation in cHGF was independent of dose or drug exposure and was restricted to 
onartuzumab treatment. Neither higher baseline nor elevated change in cHGF 
levels upon treatment could simply be attributed to tumor burden or number of 
liver metastasis. We have shown that elevated cHGF can consistently and 
reproducibly be measured as a pharmacodynamic biomarker of onartuzumab activity. 
The elevation in cHGF is independent of tumor type, dose administered, or dose 
duration. Although these studies were not powered to directly address the 
contribution of cHGF as a predictive, on-treatment, circulating biomarker, these 
data suggest that measurement of cHGF in future expanded studies is warranted.