title: A Pharmacokinetic and Safety Study of Trebananib, an Fc-Fusion Peptibody, in Patients With Advanced Solid Tumors and Varying Degrees of Renal Dysfunction.
abstract: Clearance of trebananib (AMG 386), a 64-kD antiangiogenic peptibody, has been associated with estimated glomerular filtration rate (eGFR). We prospectively evaluated trebananib pharmacokinetics and safety/tolerability in advanced solid tumor patients with varying degrees of renal function. Patients were assigned to normal renal function, mild, moderate, or severe renal dysfunction cohorts based on eGFR, received trebananib 15 mg/kg i.v. weekly, and underwent week 1 and week 5 pharmacokinetic and weekly safety assessments. For 28 patients, trebananib clearance decreased from normal renal function (1.52 mL/hr/kg), to mild (1.20 mL/hr/kg), moderate (0.79 mL/hr/kg), and severe (0.53 mL/hr/kg) renal dysfunction (P ≤ 0.001). Treatment-related adverse events showed no association with clearance. Trebananib clearance was proportional to eGFR and unrelated to pretreatment protein excretion. These data confirm a role for renal clearance of a recombinant peptibody with molecular weight <69 kD and support a longer dosing interval for patients with severe renal dysfunction.
authors.affiliation: Amgen Inc, Thousand Oaks, California, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Medicine, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Lewis
authors.affiliation: Emory University, Winship Cancer Institute, Atlanta, Georgia, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Harvey
authors.affiliation: Amgen Inc, Thousand Oaks, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Rasmussen
authors.affiliation: Amgen Inc, Thousand Oaks, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
authors.affiliation: Amgen Inc, Thousand Oaks, California, USA.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Sun
authors.affiliation: Amgen Inc, Thousand Oaks, California, USA.
authors.forename: G
authors.initials: G
authors.lastname: Friberg
authors.affiliation: University of Chicago Medicine, Chicago, Illinois, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Case Western Reserve University and University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dowlati
authors.affiliation: University of Chicago Medicine, Chicago, Illinois, USA.|Inova Schar Cancer Institute and Center for Personalized Health, Falls Church, Virginia, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Maitland
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C551398:trebananib