HGF as a circulating biomarker of onartuzumab treatment in patients with advanced solid tumors
Menée notamment sur 137 patients atteints d'un cancer du poumon non à petites cellules et inclus dans un essai de phase II de l'onartuzumab, un inhibiteur de Met, cette étude évalue l'association entre le niveau du facteur de croissance des hépatocytes dans la circulation sanguine et la réponse thérapeutique
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 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, on-treatment, circulating biomarker, these data suggest that measurement of cHGF in future expanded studies is warranted.
Molecular Cancer Therapeutics , résumé, 2013