A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1/2 neutralizing peptibody, in patients with persistent/recurrent carcinoma of the endometrium: An NRG/Gynecologic Oncology Group trial

• Published in: Gynecologic oncology 2015-09, Vol.138 (3), p.513-518
• Main Authors: Moore, Kathleen N, Sill, Michael W, Tenney, Meaghan E, Darus, Christopher J, Griffin, David, Werner, Theresa L, Rose, Peter G, Behrens, Robert
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Angiopoietin-1 - antagonists & inhibitors; Angiopoietin-1 - metabolism; Angiopoietin-2 - antagonists & inhibitors; Angiopoietin-2 - metabolism; Endometrial cancer; Endometrial Neoplasms - blood supply; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - metabolism; Female; Hematology, Oncology and Palliative Medicine; Humans; Middle Aged; NCT01210222; Obstetrics and Gynecology; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - therapeutic use; Trebananib
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2015.07.006

Abstract Objectives Ang1 & 2 (angiopoietin-1; − 2) interact with Tie2 receptors on endothelial cells to mediate vascular remodeling in an angiogenesis signaling pathway distinct from the VEGF axis. Trebananib is a peptide Fc fusion protein that binds Ang1 and 2 and prevents interaction with Tie2. The efficacy of trebananib in recurrent/persistent endometrial cancer (EC) was studied. Methods The primary objective was to determine the frequency of patients with objective tumor responses (ORR) and event-free survival for ≥ 6 months (6-month EFS) and determine toxicity of trebananib at a dose and schedule of 15 mg/kg, IV QW. Recurrent/persistent EC, measurable disease, and ≤ 2 prior chemotherapy lines were required. Results Thirty-two patients were eligible and treated. The most common histologies were G1/2 endometrioid (31%), G3 endometrioid (28%) and serous (31.3%). 78% of patients had 1 prior regimen. Patients received 1–9 + cycles of trebananib; 24 patients (75%) received ≤ 2 cycles. One patient had a partial response (3.1%); 8 patients had stable disease (25%) and 5 patients (15.6%) had 6 month EFS. Median progression-free survival and overall-survival were 1.97 months (90% CI 1.77–2.1) and 6.6 months (90% CI 4.01–14.75), respectively. Most common adverse events (AEs) were fatigue, anemia, and GI issues. Grade 3 and 4 AEs were: GI 31 and 0%; vascular 22 and 0%; metabolism/nutrition 19 and 3%; and general (including edema) 16 and 0%. Conclusions Trebananib has insufficient single agent activity in recurrent EC to warrant further investigation at this dose/schedule.