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 - 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
VL - 75
SP - 629
EP - 638
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 3
ER -