First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study

Cancers
Christoph SchliemannWolfgang E Berdel

Abstract

Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. MTD was 3 mg/m2 tTF-NGR/day × 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumo...Continue Reading

Associated Clinical Trials

References

Apr 17, 2003·Journal of the National Cancer Institute·Yukito IchinoseUNKNOWN NK421 Lung Cancer Surgery Group
Oct 11, 2005·Medicinal Research Reviews·Brigitte Bauvois, Daniel Dauzonne
Jul 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takahiro TokuharaMasayuki Miyake
Oct 3, 2006·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·P SurowiakH Lage
Jun 10, 2008·Current Drug Discovery Technologies·Torsten KesslerRolf M Mesters
Oct 8, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Manuela SchmidingerHerwig Schmidinger
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alok A Khorana, Gregory C Connolly
Apr 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Vanesa GregorcClaudio Bordignon
May 15, 2010·Thrombosis Research·Christian SchwöppeWolfgang E Berdel
Jan 6, 2011·Cancer Science·Malin WickströmJoachim Gullbo
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Nov 23, 2011·Circulation·Vinay S Mahajan, Petr Jarolim
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Liliana Guzman-RojasRenata Pasqualini
Feb 15, 2013·Thrombosis and Haemostasis·Josef EhlingFabian Kiessling
Mar 19, 2013·Journal of Medicinal Chemistry·Christian SchwöppeWolfgang E Berdel
Jun 8, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Angelo CortiVanesa Gregorc
Aug 28, 2013·Nature Reviews. Cardiology·Evangelos Giannitsis, Hugo A Katus
Feb 1, 2014·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·B L FaintuchA M Moro
Jan 15, 2015·Journal of Labelled Compounds & Radiopharmaceuticals·Dae-Weung KimChang Guhn Kim
Jan 17, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Gábor MátéGyörgy Trencsényi
Dec 29, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alok A KhoranaAgnes Y Y Lee
Jun 13, 2017·PloS One·Lars Henning SchmidtWolfgang Hartmann
Nov 8, 2017·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Lars Henning SchmidtWolfgang Hartmann
Feb 6, 2019·Nature Reviews. Clinical Oncology·Mirjam GerwingMoritz Wildgruber
May 17, 2019·Seminars in Thrombosis and Hemostasis·Araci M R RondonJeroen T Buijs
Sep 22, 2019·Science Immunology·Claudine GrafWolfram Ruf

❮ Previous
Next ❯

Methods Mentioned

BETA
contraception
enzyme-linked immunosorbent assay
ELISA
dissection
xenograft

Clinical Trials Mentioned

NCT02902237

Software Mentioned

IntelliSpace
VueBox ® Quantification Toolbox
PKSolver
BRACCO

Related Concepts

Related Feeds

Cancer Imaging

Imaging techniques, including CT and MR, have become essential to tumor detection, diagnosis, and monitoring. Here is the latest research on cancer imaging.