title: A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors.
abstract: OBJECTIVE
  A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507-a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor.
  
  
  METHODS
  Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease.
  
  
  RESULTS
  In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors.
  
  
  CONCLUSIONS
  R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW.
authors.affiliation: Department of Investigational Cancer Therapeutics, M.D. Anderson Cancer Center, Houston, TX 77030, USA. rkurzroc@mdanderson.org
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
authors.forename: Joseph
authors.initials: J
authors.lastname: Aisner
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.forename: Stephen
authors.initials: S
authors.lastname: Leong
authors.forename: Robert
authors.initials: R
authors.lastname: Benjamin
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Eid
authors.forename: Gerard
authors.initials: G
authors.lastname: Greig
authors.forename: Kai
authors.initials: K
authors.lastname: Habben
authors.forename: Cinara D
authors.initials: CD
authors.lastname: McCarthy
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017526:Receptor, IGF Type 1; C551399:teprotumumab