title: A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.
abstract: BACKGROUND
  Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.
  
  
  METHODS
  This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics.
  
  
  RESULTS
  Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib).
  
  
  CONCLUSIONS
  The toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: dshong@mdanderson.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Pinnacle Oncology Hematology, Scottsdale, AZ.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.affiliation: Comprehensive Cancer Centers of Nevada and US Oncology, Las Vegas, NV.
authors.forename: Wolfram E
authors.initials: WE
authors.lastname: Samlowski
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Nizar
authors.initials: N
authors.lastname: Tannir
authors.affiliation: Hillman Cancer Center, Pittsburgh, PA.
authors.forename: David
authors.initials: D
authors.lastname: Friedland
authors.affiliation: Pinnacle Oncology Hematology, Scottsdale, AZ.
authors.forename: David S
authors.initials: DS
authors.lastname: Mendelson
authors.affiliation: Comprehensive Cancer Centers of Nevada and US Oncology, Las Vegas, NV.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Erik
authors.initials: E
authors.lastname: Rasmussen
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wu
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bass
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Zhandong D
authors.initials: ZD
authors.lastname: Zhong
authors.affiliation: Amgen Inc, Thousand Oaks, CA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Friberg
authors.affiliation: Hillman Cancer Center, Pittsburgh, PA.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Appleman
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib; C551398:trebananib
keywords: Angiogenesis; Angiopoietins; Targeted therapies; Tie2 receptor; Vascular growth factor receptor