Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours.

ESMO Open
Walter FiedlerSara De Dosso

Abstract

TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies and to define the safety, pharmacokinetics (PK) and preliminary antitumour activity of TrasGEX. A total of 37 patients with advanced HER2-positive carcinomas and progressive disease received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose. No dose limiting toxicity was observed, and no maximum tolerated dose was reached. Drug-related adverse events were mainly infusion-related reactions occurring during the first infusion in 51% of patients; all but two were mild-to-moderate. Compared with trastuzumab, the PK parameters were dose dependent, with a mean terminal half-life (t1/2) of 263±99 hours for the 720 mg dose. Clinical benefit in 15 out of 30 (50%) evaluable patients included one ongoing complete response, two partial remissions lasti...Continue Reading

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References

Mar 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J BaselgaL Norton
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Sep 26, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian Leyland-JonesParviz Ghahramani
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberto GennariAlberto Costa
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rinpei NiwaKenya Shitara
May 4, 2005·Cancer Chemotherapy and Pharmacology·Rene BrunoPamela Klein
Mar 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eiji SuzukiMasakazu Toi
Jul 6, 2007·The New England Journal of Medicine·Clifford A Hudis
Mar 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonino MusolinoAndrea Ardizzoni
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Nov 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neil L Spector, Kimberly L Blackwell
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert L FerrisSoldano Ferrone
Apr 17, 2012·Journal of the American Academy of Dermatology·Alice P ChenMario E Lacouture
Apr 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sara A HurvitzJohn M Timmerman
Feb 1, 2014·The Lancet Oncology·Giampaolo Bianchini, Luca Gianni

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Methods Mentioned

BETA
glycosylation
genotyping

Clinical Trials Mentioned

NCT01409343

Software Mentioned

SAS

Related Concepts

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