title: Alliance A091103 a phase II study of the angiopoietin 1 and 2 peptibody trebananib for the treatment of angiosarcoma.
abstract: BACKGROUND
  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: Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA, dangelos@mskcc.org.
authors: Sandra P
authors: SP
authors: D' Angelo
authors: Michelle R
authors: MR
authors: Mahoney
authors: Brian A
authors: BA
authors: Van Tine
authors: Douglas R
authors: DR
authors: Adkins
authors: Maria T Grosse
authors: MT
authors: Perdekamp
authors: Mercedes M
authors: MM
authors: Condy
authors: Jason J
authors: JJ
authors: Luke
authors: Eliza Woodward
authors: EW
authors: Hartley
authors: Cristina R
authors: CR
authors: Antonescu
authors: William D
authors: WD
authors: Tap
authors: Gary K
authors: GK
authors: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006394:Hemangiosarcoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D011993:Recombinant Fusion Proteins; C551398:trebananib