title: A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.
abstract: OBJECTIVE
  This phase Ib study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 102, a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in combination with bevacizumab or motesanib in patients with advanced solid tumors.
  
  
  METHODS
  Patients with treatment-refractory advanced solid tumors were sequentially enrolled into four cohorts (3, 10, or 20 mg/kg AMG 102 plus 10 mg/kg bevacizumab i.v. every 2 weeks, or 3 mg/kg AMG 102 i.v. every 2 weeks plus 75 mg motesanib orally once daily).
  
  
  RESULTS
  Fourteen patients were enrolled and received AMG 102. The combination of AMG 102 with bevacizumab (n = 12) seemed to have acceptable toxicity. The number of patients (n = 2) who received AMG 102 plus motesanib was insufficient to adequately assess safety. No dose-limiting toxicities were reported. Enrollment in the motesanib cohort was suspended because of reports of cholecystitis in other motesanib studies. Treatment-emergent adverse events among patients receiving AMG 102 plus bevacizumab were generally mild and included fatigue (75%), nausea (58%), constipation (42%), and peripheral edema (42%). No anti-AMG 102 antibodies were detected. Bevacizumab did not seem to affect AMG 102 pharmacokinetics. Circulating total HGF/SF increased from baseline throughout the study. Eight of 10 evaluable patients had reductions in tumor dimensions, and stable disease at > or =8, > or =16, and > or =24 weeks occurred in 9, 7, and 4 patients, respectively. Progression-free survival ranged from 7.9 to 121.9 weeks.
  
  
  CONCLUSIONS
  AMG 102 in combination with bevacizumab was well tolerated. Further evaluation of AMG 102 in combination with antiangiogenic agents is warranted.
authors.affiliation: Tower Cancer Research Foundation, Beverly Hills, California 90210, USA. rosenp@toweroncology.com
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rosen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Park
authors.forename: Darrin M
authors.initials: DM
authors.lastname: Beaupre
authors.forename: Hongjie
authors.initials: H
authors.lastname: Deng
authors.forename: Ian M
authors.initials: IM
authors.lastname: Leitch
authors.forename: Poornima
authors.initials: P
authors.lastname: Shubhakar
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.forename: Abraham
authors.initials: A
authors.lastname: Anderson
authors.forename: Lorrin K
authors.initials: LK
authors.lastname: Yee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D000068258:Bevacizumab; D015331:Cohort Studies; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009841:Oligonucleotides; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; D000068258:Bevacizumab; C524459:rilotumumab; D017228:Hepatocyte Growth Factor; C519562:imetelstat