title: A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours.
abstract: BACKGROUND
  TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid tumours.
  
  
  METHODS
  Patients in sequential dose groups received either weekly doses of 1.25, 5.0, or 10 mg kg(-1) or doses of 20 or 30 mg kg(-1) every third week.
  
  
  RESULTS
  Twenty-three patients were enrolled and received TB-403. The most common adverse events (AEs) were fatigue, constipation, pyrexia, dyspnoea, and nausea. One serious AE, a lung embolus in a patient with non-small cell lung cancer treated with 10 mg kg(-1) weekly, was deemed possibly related to TB-403. No dose-limiting toxicities were observed, and a maximum-tolerated dose was not reached. The PK parameters were dose linear and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg(-1) weekly, remained stable for 12 months.
  
  
  CONCLUSIONS
  TB-403 treatment in this patient population is well tolerated, with a safety profile distinct from that of vascular endothelial growth factor-axis inhibitors.
authors.affiliation: Department of Oncology 5073, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ulrik.lassen@rh.regionh.dk
authors.forename: U
authors.initials: U
authors.lastname: Lassen
authors.forename: D L
authors.initials: DL
authors.lastname: Nielsen
authors.forename: M
authors.initials: M
authors.lastname: Sørensen
authors.forename: L
authors.initials: L
authors.lastname: Winstedt
authors.forename: T
authors.initials: T
authors.lastname: Niskanen
authors.forename: Y
authors.initials: Y
authors.lastname: Stenberg
authors.forename: S
authors.initials: S
authors.lastname: Pakola
authors.forename: J-M
authors.initials: JM
authors.lastname: Stassen
authors.forename: S
authors.initials: S
authors.lastname: Glazer
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000276:immunology*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C569915:TB-403