title: Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
abstract: OBJECTIVE
  This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma.
  
  
  METHODS
  Patients with refractory/relapsed melanoma received 15 mg/kg tremelimumab every 90 days. After 4 doses, patients with tumor response or stable disease were eligible to receive < or =4 additional doses. Primary endpoint was best overall tumor response assessed by an independent endpoint review committee, and secondary endpoints included duration of response, overall survival, progression-free survival, and safety.
  
  
  RESULTS
  Of 251 patients enrolled, 246 (241 response-evaluable) received tremelimumab. Objective response rate was 6.6% (16 partial responses); duration of response was 8.9 to 29.8 months. Eight (50%) objective responses occurred in patients with stage IV M(1c) disease, and 11 (69%) were ongoing at last tumor assessment. Eight (3.3%) patients achieved responses in target lesions (Response Evaluation Criteria in Solid Tumors) despite progressive disease within the first cycle. All 8 survived for >20 months; 5 (63%) remained alive. Clinical benefit rate (overall response + stable disease) was 21% (16 partial responses and 35 stable disease), and median overall survival was 10.0 months. Progression-free survival at 6 months was 15%, and survival was 40.3% at 12 months and 22% at 24 months. Common treatment-related adverse events were generally mild to moderate, and grade 3/4 adverse events included diarrhea (n = 28, 11%), fatigue (n = 6, 2%), and colitis (n = 9, 4%). There were 2 (0.8%) treatment-related deaths.
  
  
  CONCLUSIONS
  Tremelimumab showed an objective response rate of 6.6%, with all responses being durable > or =170 days since enrollment, suggesting a potential role for tremelimumab in melanoma.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. kirkwoodjm@upmc.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: David
authors.initials: D
authors.lastname: McDermott
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Marshall
authors.forename: Jesus
authors.initials: J
authors.lastname: Gomez-Navarro
authors.forename: Jane Q
authors.initials: JQ
authors.lastname: Liang
authors.forename: Cecile A
authors.initials: CA
authors.lastname: Bulanhagui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D012008:Recurrence; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C520704:tremelimumab