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Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies.

Authors :
Heil F
Babitzki G
Julien-Laferriere A
Ooi CH
Hidalgo M
Massard C
Martinez-Garcia M
Le Tourneau C
Kockx M
Gerber P
Rossomanno S
Krieter O
Lahr A
Wild N
Harring SV
Lechner K
Source :
Translational oncology [Transl Oncol] 2021 Feb; Vol. 14 (2), pp. 100984. Date of Electronic Publication: 2020 Dec 15.
Publication Year :
2021

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.<br />Competing Interests: Declaration of Competing Interest The following authors are employees and shareholders of Roche Diagnostics GmbH: FH, GB, OK, SVH, KL; AJL is an employee of Soladis GmbH; CHO is an employee and shareholder of F. Hoffmann-La Roche AG; PG was an employee of Roche Innovation Center at the time of manuscript preparation, now retired; SR is an employee of F. Hoffmann-La Roche; AL and NW are employees of Roche Diagnostics GmbH; MH has received honoraria for acting as a speaker, consultant or advisory board member (Celgene, Pfizer, Novartis, MSD, EMD, Ipsem, Shire, SOBI, Champions Oncology, Agenus, Erytech, Pharmacyte, Bioline, BioOncotech, Oncomatrix, VCN, Bayer, BMS, Nelum, Eng T Cells), holds stock (Champions Oncology, Pharmacyte, BioOncotech, Nelum, Eng T Cell), and has received royalties (Myriad) and financial support paid to his institution for clinical trials or research grants (Berg, Bioline, Pfizer, EMD, Celgene, ASANA, Bycicle, Oncomatrix, BioExcell, Erytech); CM has acted as principal/sub-investigator of clinical trials (AbbVie, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare AG, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech AG, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech, Inc., Gilead Sciences, Inc, GlaxoSmithKline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, F. Hoffmann-La Roche AG, Incyte Corporation, Innate Pharma, Iris Servier, Janssen Cilag, Kura Oncology, Kyowa Kirin Pharm, Eli Lilly, Loxo Oncology, Lytix Biopharma AS, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology NV, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec GmbH, F. Hoffmann-La Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Inc., Tioma Therapeutics, Inc., Xencor), received research grants (AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, F. Hoffmann-La Roche, Sanofi), received non-financial support (drug supplied) (AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Eli Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche) and received consultant/advisory fees (Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Eli Lilly, MedImmune, Novartis, Pfizer, F. Hoffmann-La Roche, Sanofi, Orion); MMG has acted as consultant/advisory board member (F. Hoffmann-La Roche) and received travel expenses (F. Hoffmann-La Roche, Pfizer); ClT has participated in advisory boards (AstraZeneca, F. Hoffmann-La Roche, MSD, BMS, Merck Serono, GSK, Nanobiotix, Amgen); MK is a co-founder and shareholder of HistoGeneX N.V.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1936-5233
Volume :
14
Issue :
2
Database :
MEDLINE
Journal :
Translational oncology
Publication Type :
Academic Journal
Accession number :
33338877
Full Text :
https://doi.org/10.1016/j.tranon.2020.100984