Alliance A091103 a phase II study of the angiopoietin 1 and 2 peptibody trebananib for the treatment of angiosarcoma. Academic Article uri icon

Overview

abstract

  • INTRODUCTION: Angiosarcomas are rare malignant endothelial cell tumors which have up-regulation of the angiopoietin system [e.g., Tie2 and Angiopoietin 2 (Ang2)]. Trebananib is a novel agent targeting Angiopoietin 1 and Angiopoietin 2. METHODS: Trebananib 30 mg/kg was administered weekly until progressive disease or unacceptable toxicity. The primary endpoint was response rate by RECIST v1.1. Correlatives included: (1) baseline tumor expression of Ang2/Tie2 by immunohistochemistry, (2) serum levels of Ang1 and Ang2, (3) pre- and post-treatment phospho-receptor tyrosine kinase and (4) MYC/FLT-4 amplification status. RESULTS: Sixteen patients were enrolled [median age 68 years (24-91), 38 % male, median number of prior therapies 2.5 (1-7)]. No responses were observed in 12 evaluable patients. Estimated median and 12-week progression-free survival rate were 7 weeks (95 % 6-8) and 25 % (95 % CI 11-58 %), respectively. Median overall survival was 28 weeks (95 % CI 17-48). There were two (12.5 %) patients who experienced grade 3 adverse event and one (6.3 %) patient who experienced grade 4 adverse event that was considered at least possibly related to treatment. CONCLUSIONS: Trebananib was well tolerated. Lack of response in the first stage of a Simon 2 stage design led to closure of this study. Prolonged PFS was observed in four pts, lasting 3.4-5.5 months.

authors

  • D'Angelo, Sandra
  • Mahoney, Michelle R
  • Van Tine, Brian A
  • Adkins, Douglas R
  • Perdekamp, Maria T Grosse
  • Condy, Mercedes M
  • Luke, Jason J
  • Hartley, Eliza Woodward
  • Antonescu, Cristina R
  • Tap, William
  • Schwartz, Gary K

publication date

  • February 12, 2015

Research

keywords

  • Angiogenesis Inhibitors
  • Angiopoietin-1
  • Angiopoietin-2
  • Hemangiosarcoma
  • Recombinant Fusion Proteins

Identity

PubMed Central ID

  • PMC4699670

Scopus Document Identifier

  • 84925497823

Digital Object Identifier (DOI)

  • 10.1007/s00280-015-2689-8

PubMed ID

  • 25672915

Additional Document Info

volume

  • 75

issue

  • 3