title: A Phase I study of MEDI-575, a PDGFRα monoclonal antibody, in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  MEDI-575 is a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor alpha (PDGFRα). This open-label Phase I study assessed the safety and tolerability of MEDI-575 in Japanese patients with advanced solid tumors.
  
  
  METHODS
  The study comprised two parts: Part A, dose escalation; Part B, dose expansion in patients with hepatocellular cancer. In Part A, patients were enrolled into three cohorts: MEDI-575 was administered intravenously over a 21-day treatment cycle at doses of 9 and 15 mg/kg/week (cohorts 1, 2) and 35 mg/kg/3-weekly (cohort 3). In Part B, MEDI-575 25 mg/kg/3-weekly was administered. Secondary measures included assessment of the maximum tolerated dose, pharmacokinetics, immunogenicity and anti-tumor activity.
  
  
  RESULTS
  Ten and 12 patients were treated in Parts A and B, respectively. There were no dose-limiting toxicities; the maximum tolerated dose was not determined. Common treatment-related adverse events were fatigue (30%) and decreased appetite (20%) in Part A and decreased appetite (33.3%) in Part B. All treatment-related adverse events were grade 1 or 2 in severity. No patients discontinued MEDI-575 because of an adverse event and there were no patient deaths due to adverse events. MEDI-575 binding with PDGFRα resulted in a dose-dependent increase in PDGF-AA ligand, with plateau levels observed within 2 days and sustained during the dosing interval. None of the patients in Part A or B experienced complete or partial responses to treatment.
  
  
  CONCLUSIONS
  MEDI-575 once weekly and 3-weekly was well tolerated with a favorable pharmacokinetic profile in Japanese patients with advanced solid tumors.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01102400.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho Sunto-Gun, Shizuoka, 411-8777, Japan, ha.murakami@scchr.jp.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
authors.forename: Katsuro
authors.initials: K
authors.lastname: Yagawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C000594804:Tovetumab; D020796:Receptor, Platelet-Derived Growth Factor alpha