Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies
Florian Heil, Galina Babitzki, Alice Julien-Laferrière, Chia-Huey Ooi, Manuel Hidalgo, Christophe Massard, Maria Martinez‐García, Christophe Le Tourneau, Mark Kockx, Peter Arne Gerber, Simona Rossomanno, Oliver Krieter, Angelika Lahr, Norbert Wild, Suzana Vega Harring, Katharina Lechner
Abstract
Vanucizumab is a novel bispecific antibody inhibiting vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2) that demonstrated safety and anti-tumor activity in part I of a phase I study of 42 patients with advanced solid tumors. Part II evaluated the pharmacodynamic effects of vanucizumab 30 or 15 mg/kg every 2 weeks in 32 patients. Serial plasma samples, paired tumor, and skin-wound-healing biopsies were taken over 29 days to evaluate angiogenic markers. Vanucizumab was associated with marked post-infusion reductions in circulating unbound VEGF-A and Ang-2. By day 29, tumor samples revealed mean reductions in density of microvessels (-32.2%), proliferating vessels (-47.9%) and Ang-2 positive vessels (-62.5%). Skin biopsies showed a mean reduction in density of microvessels (-49.0%) and proliferating vessels (-25.7%). Gene expression profiling of tumor samples implied recruitment and potential activation of lymphocytes. Biopsies were safely conducted. Vanucizumab demonstrated a consistent biological effect on vascular-related biomarkers, confirming proof of concept. Skin-wound-healing biopsies were a valuable surrogate for studying angiogenesis-related mechanisms.