A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours.

British Journal of Cancer
U LassenSteven Glazer

Abstract

TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid tumours. Patients in sequential dose groups received either weekly doses of 1.25, 5.0, or 10 mg kg(-1) or doses of 20 or 30 mg kg(-1) every third week. Twenty-three patients were enrolled and received TB-403. The most common adverse events (AEs) were fatigue, constipation, pyrexia, dyspnoea, and nausea. One serious AE, a lung embolus in a patient with non-small cell lung cancer treated with 10 mg kg(-1) weekly, was deemed possibly related to TB-403. No dose-limiting toxicities were observed, and a maximum-tolerated dose was not reached. The PK parameters were dose linear and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg(-1) weekly, remained stable for 12 months. TB-403 treatment in this patient population is well tolerated, with a safety profile distinct from that of vascular e...Continue Reading

References

Jul 1, 1992·Immunology Today·A MantovaniL Ruco
Apr 4, 2003·International Journal of Cancer. Journal International Du Cancer·Alice P TaylorRosalyn D Blumenthal
Jun 5, 2003·Nature Medicine·Peter Carmeliet
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Nov 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher G WillettGregory Y Lauwers
Dec 16, 2005·Nature·Napoleone Ferrara, Robert S Kerbel
Mar 28, 2006·Cell·J Wade Harper, Brenda A Schulman
Sep 13, 2006·Cancer Metastasis Reviews·Alberto MantovaniAntonio Sica
Nov 14, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ferry A L M Eskens, Jaap Verweij
Jan 12, 2007·The New England Journal of Medicine·Bernard EscudierUNKNOWN TARGET Study Group
Apr 26, 2007·Nature Reviews. Cancer·Thomas ForceRichard A Van Etten
May 25, 2007·Nature Reviews. Cancer·Henk M W Verheul, Herbert M Pinedo
Oct 16, 2007·Drug Discovery Today·Francesco BertoliniRobert S Kerbel
Mar 14, 2008·The New England Journal of Medicine·Vera EreminaSusan E Quaggin
May 9, 2008·The New England Journal of Medicine·Robert S Kerbel
Jul 18, 2008·Nature Reviews. Cancer·Craig MurdochClaire E Lewis
Aug 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian I RiniDaniel J George
Sep 17, 2008·Cancer Research·Mark KerberMarcia Regina Machein
Nov 26, 2008·Nature Reviews. Cancer·Christian FischerPeter Carmeliet
May 1, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M Dror MichaelsonM R Smith
May 28, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sonja LogesPeter Carmeliet
May 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher G WillettRakesh K Jain
Jul 28, 2009·The Annals of Thoracic Surgery·Eugenio PompeoTommaso C Mineo
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott KopetzJohn V Heymach

❮ Previous
Next ❯

Citations

Dec 24, 2013·Cancer Treatment Reviews·Gabriel Limaverde-SousaCarlos Gil Ferreira
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jenny YaoCarlos Bais
Sep 6, 2013·International Journal of Molecular Sciences·Karin ZinsDietmar Abraham
Dec 11, 2014·The Journal of Investigative Dermatology·Ichiro YajimaMasashi Kato
Oct 10, 2014·Expert Opinion on Therapeutic Targets·Mieke Dewerchin, Peter Carmeliet
Apr 18, 2012·Expert Opinion on Biological Therapy·Dorte Lisbet Nielsen, Lisa Sengeløv
Oct 13, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sarah RaevensIsabelle Colle
Mar 7, 2013·Endocrine-related Cancer·Georg HilfenhausChristian Fischer
May 8, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sarah Raevens, Michael B Fallon
Mar 20, 2015·Journal of the American Society of Nephrology : JASN·Masaru MatsuiUNKNOWN NARA-CKD Investigators
Jul 30, 2015·The Cancer Journal·Ana BatistaRakesh K Jain
Apr 28, 2017·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Hamid Reza NejabatiMohammad Nouri
Jul 10, 2012·The Oncologist·Sabine TejparMassimiliano Mazzone
Jun 21, 2019·International Journal of Molecular Sciences·Loredana AlboniciRoberto Bei
Apr 30, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Thijs H Oude MunninkElisabeth G E de Vries

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
ELISA
flow cytometry

Clinical Trials Mentioned

NCT00702494

Software Mentioned

WinNonLinPro

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.