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

  • Gynecol Oncol. 2015 Sep;138(3):513-8. doi: 10.1016/j.ygyno.2015.07.006.
Kathleen N Moore  1 ,  Michael W Sill  2 ,  Meaghan E Tenney  3 ,  Christopher J Darus  4 ,  David Griffin  5 ,  Theresa L Werner  6 ,  Peter G Rose  7 ,  Robert Behrens  8
Affiliations
  • 1. Stephenson Oklahoma Cancer Center, 800 NE 10th Street, Oklahoma City, OK 73104, United States. Electronic address: [email protected].
  • 2. NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States. Electronic address: [email protected].
  • 3. University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, United States. Electronic address: [email protected].
  • 4. Maine Medical Center, 102 Campus Drive Unit 116, Scarborough, ME 04074, United States. Electronic address: [email protected].
  • 5. Upstate Carolina CCOP Oncology Research, 101 East Wood Street, Spartanburg, SC 29303, United States. Electronic address: [email protected].
  • 6. Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, United States. Electronic address: [email protected].
  • 7. Cleveland Clinic Foundation, 9500 Euclid Avenue, A81, Cleveland, OH 44106, United States. Electronic address: [email protected].
  • 8. Cancer Center of Iowa, Iowa Wide Oncology Research Coalition, 1221 Pleasant Street, Suite 450, Des Moines IA 50309, United States. Electronic address: [email protected].
PMID: 26171911 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 ≥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.

Keywords
Angiogenesis; Endometrial cancer; NCT01210222; Trebananib.
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