title: A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  • To evaluate the efficacy and safety of single-agent AMG 102, an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), in renal cell carcinoma (RCC).
  
  
  METHODS
  • This open-label phase II study included patients ≥ 18 years old with histologically confirmed, advanced or metastatic RCC (mRCC) and Eastern Cooperative Oncology Group performance status 0 to 2. AMG 102 was administered i.v. at 10 or 20 mg/kg once every 2 weeks. • A two-stage design was used at each dose level and the primary endpoint was objective best confirmed response (by Response Evaluation Criteria in Solid Tumours) at any time.
  
  
  RESULTS
  • Sixty-one patients with mRCC enrolled and received AMG 102 (40 at 10 mg/kg; 21 at 20 mg/kg). Overall, 70.5% were men, median age was 59 years (range, 39 to 84 years), and 92% had received previous anti-vascular endothelial growth factor therapy. RCC histologies were: clear cell (75.4%), papillary (11.5%), chromophobe (4.9%) and unclassified (8.2%). • One confirmed partial response occurred at 10 mg/kg, maintained for over 2.5 years; 26 patients (43%) had stable disease, 10 (16%) for ≥ 32 weeks. The median profression-free survival was 3.7 months at 10 mg/kg and 2.0 months at 20 mg/kg. The commonest adverse events were oedema (45.9%), fatigue (37.7%) and nausea (27.9%). Grade 3 or 4 adverse events occurred in 33% of patients, the most common being oedema (9.8%). • Baseline levels of plasma HGF/SF and soluble c-Met as well as archival-tumour c-Met did not correlate with measures of efficacy.
  
  
  CONCLUSIONS
  • Single-agent AMG 102 was tolerable, but it is unclear if AMG 102 was growth inhibitory in this population of patients with mRCC.
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium. patrick.schoffski@uz.kuleuven.be
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Thierry
authors.initials: T
authors.lastname: Gil
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Melanie
authors.initials: M
authors.lastname: Smitt
authors.forename: Xinqun
authors.initials: X
authors.lastname: Yang
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.forename: Abraham
authors.initials: A
authors.lastname: Anderson
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C066855:HGF protein, human; C524459:rilotumumab; D017228:Hepatocyte Growth Factor