HGF as a Circulating Biomarker of Onartuzumab Treatment in Patients with Advanced Solid Tumors

E. Penuel, C. Li, V. Parab, L. Burton, K. J. Cowan, M. Merchant, R. L. Yauch, P. Patel, A. Peterson, G. M. Hampton, M. R. Lackner, P. S. Hegde
2013 Molecular Cancer Therapeutics  
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 intravenously once every three weeks. The Phase II study was a randomized two-arm trial in which onartuzumab or placebo was administered in
more » ... was administered in combination with erlotinib in 137 patients with second and third line (2/3L) NSCLC. Circulating HGF (cHGF) levels were evaluated by enzyme-linked immunosorbent assay (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 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. While these studies were not powered to directly address the contribution of cHGF as a predictive, ontreatment, circulating biomarker, these data suggest that measurement of cHGF in future expanded studies is warranted.
doi:10.1158/1535-7163.mct-13-0015 pmid:23536720 fatcat:m6hqnoj7vja3hpbjrgy2apsvva