TY - JOUR
T1 - Alliance A091103 a phase II study of the angiopoietin 1 and 2 peptibody trebananib for the treatment of angiosarcoma
AU - D'Angelo, Sandra P.
AU - Mahoney, Michelle R.
AU - Van Tine, Brian A.
AU - Adkins, Douglas R.
AU - Perdekamp, Maria T.Grosse
AU - Condy, Mercedes M.
AU - Luke, Jason J.
AU - Hartley, Eliza Woodward
AU - Antonescu, Cristina R.
AU - Tap, William D.
AU - Schwartz, Gary K.
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2015 Springer-Verlag Berlin Heidelberg.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
KW - Angiopoietin system
KW - Angiosarcoma
KW - Trebananib
UR - http://www.scopus.com/inward/record.url?scp=84925497823&partnerID=8YFLogxK
U2 - 10.1007/s00280-015-2689-8
DO - 10.1007/s00280-015-2689-8
M3 - Article
C2 - 25672915
AN - SCOPUS:84925497823
SN - 0344-5704
VL - 75
SP - 629
EP - 638
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 3
ER -