A phase Ib dose-escalation study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A) in combination with bevacizumab with or without paclitaxel in patients with advanced solid tumors.

2514 Background: Epidermal growth factor-like domain 7 (EGFL7), is a vascular-restricted, tumor selective, extracellular matrix protein that forms perivascular tracks and promotes endothelial cell adhesion and survival, especially under stress. Anti-EGFL7 (MEGF0444A) is a huMAb that inhibits these activities of EGFL7. In combination with an anti-VEGF antibody, anti-EGFL7 significantly enhances the anti-tumor activity of anti-VEGF in multiple murine tumor models. Methods: A standard 3+3 dose escalation design was used to study safety, PK, PD and anti-tumor activity in 40 patients (pts) with advanced solid tumors. In Arm A, MEGF0444A was given IV at doses of 2, 5 or 10 mg/kg followed by bevacizumab IV at 10 mg/kg on Days 1 and 15 of each 28-day cycle. Pts in Arm B also received paclitaxel (90 mg/m2) on Days 1, 8 and 15 of each 28 day cycle. PD biomarkers including circulating progenitor cells (CPC) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) were assessed. Results: The combination of ...