Alliance A091103 a phase II study of the angiopoietin 1 and 2 peptibody trebananib for the treatment of angiosarcoma

作者：D'Angelo Sandra P^*; 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 D; Schwartz Gary K

来源：Cancer Chemotherapy and Pharmacology, 2015, 75(3): 629-638.

DOI：10.1007/s00280-015-2689-8

• Angiosarcoma
• Trebananib
• Angiopoietin system

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.
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.
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.
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.

• 出版日期2015-3