title: 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: OBJECTIVE
  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.affiliation: Stephenson Oklahoma Cancer Center, 800 NE 10th Street, Oklahoma City, OK 73104, United States. Electronic address: Kathleen-Moore@ouhsc.edu.
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
authors.affiliation: NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States. Electronic address: msill@gogstats.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, United States. Electronic address: mtenney@babies.bsd.uchicago.edu.
authors.forename: Meaghan E
authors.initials: ME
authors.lastname: Tenney
authors.affiliation: Maine Medical Center, 102 Campus Drive Unit 116, Scarborough, ME 04074, United States. Electronic address: darusc@mmc.org.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Darus
authors.affiliation: Upstate Carolina CCOP Oncology Research, 101 East Wood Street, Spartanburg, SC 29303, United States. Electronic address: david_griffin@bshsi.org.
authors.forename: David
authors.initials: D
authors.lastname: Griffin
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, United States. Electronic address: theresa.werner@hci.utah.edu.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Werner
authors.affiliation: Cleveland Clinic Foundation, 9500 Euclid Avenue, A81, Cleveland, OH 44106, United States. Electronic address: rosep@ccf.org.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.affiliation: Cancer Center of Iowa, Iowa Wide Oncology Research Coalition, 1221 Pleasant Street, Suite 450, Des Moines IA 50309, United States. Electronic address: rbehrens@cancercenterofiowa.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Behrens
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D042683:Angiopoietin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D011993:Recombinant Fusion Proteins; C551398:trebananib
keywords: Angiogenesis; Endometrial cancer; NCT01210222; Trebananib