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.

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 ≥6months (6-month EFS) and determine toxicity of trebananib at a dose and schedule of 15mg/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 ≤2cycles. 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.

• Authors: Kathleen N Moore, Michael W Sill, Meaghan E Tenney, Christopher J Darus, David Griffin, Theresa L Werner, Peter G Rose, Robert Behrens
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 138 Issue 3 Pg. 513-8 (Sep 2015) ISSN: 1095-6859 [Electronic] United States
• PMID: 26171911 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• ANGPT1 protein, human
• ANGPT2 protein, human
• Angiogenesis Inhibitors
• Angiopoietin-1
• Angiopoietin-2
• Recombinant Fusion Proteins
• trebananib

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Angiopoietin-1 (antagonists & inhibitors, metabolism)
• Angiopoietin-2 (antagonists & inhibitors, metabolism)
• Endometrial Neoplasms (blood supply, drug therapy, metabolism)
• Female
• Humans
• Middle Aged
• Recombinant Fusion Proteins (adverse effects, therapeutic use)