A phase I study of ABT-510 plus bevacizumab in advanced solid tumors

Cancer Med. 2013 Jun;2(3):316-24. doi: 10.1002/cam4.65. Epub 2013 Mar 21.

Abstract

Targeting multiple regulators of tumor angiogenesis have the potential to improve treatment efficacy. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor and ABT-510 is a synthetic analog of thrombospondin, an endogenous angiogenesis inhibitor. Dual inhibition may result in additional benefit. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus ABT-510 in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Thirty-four evaluable subjects were enrolled and received study drug. Therapy was well tolerated; minimal treatment-related grade 3/4 toxicity was observed. One patient treated at dose level 1 had a partial response and five other patients treated at the recommended phase II dose had prolonged stable disease for more than 1 year. Biomarker evaluation revealed increased levels of D-dimer, von Willebrand factor, placental growth factor, and stromal-derived factor 1 in response to treatment with the combination of bevacizumab and ABT-510. Data suggest that continued evaluation of combination antiangiogenesis therapies may be clinically useful.

Keywords: ABT-510; advanced solid tumors; bevacizumab; phase I.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bevacizumab
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt
  • Oligopeptides
  • Bevacizumab