title: Phase I/II study of ipilimumab for patients with metastatic melanoma.
abstract: OBJECTIVE
  The primary objective of this phase I/II study was to determine the safety and pharmacokinetic profile of either transfectoma- or a hybridoma-derived ipilimumab. Secondary objectives included determination of a maximum-tolerated dose and assessment of clinical activity.
  
  
  METHODS
  Eighty-eight patients with unresectable stage III or IV melanoma with at least one measurable lesion were treated. Mean age was 59 years, with 65% male and 35% female patients, and 79% of patients had received prior systemic therapy. Single doses of ipilimumab up to 20 mg/kg (group A, single dose), multiple doses up to 5 mg/kg (group A, multiple dose), and multiple doses up to 10 mg/kg (group B) were administered.
  
  
  RESULTS
  Single dosing up to 20 mg/kg of transfectoma antibody was well tolerated, as were multiple doses up to 10 mg/kg without a maximum-tolerated dose. In group B, dose-limiting toxicity was seen in six of 23 melanoma patients. Grade 3 or 4 immune-related adverse events (irAEs) were observed in 14% of patients (12 of 88 patients), and grade 1 or 2 irAEs were seen in an additional 58%. The half-life of ipilimumab was 359 hours. In group B, there was one partial response (23+ months), one complete response (21+ months), and seven patients with stable disease (SD), for a disease control rate of 39%. Two patients in group B with SD had slow, steady decline in tumor burden that was ongoing at 1 year of observation.
  
  
  CONCLUSIONS
  Ipilimumab has activity in patients with metastatic melanoma. Late responses were observed in patients with prolonged SD.
authors.affiliation: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA. jeffrey.weber@moffitt.org
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Walter
authors.initials: W
authors.lastname: Urba
authors.forename: John
authors.initials: J
authors.lastname: Powderly
authors.forename: Geoff
authors.initials: G
authors.lastname: Nichol
authors.forename: Michael
authors.initials: M
authors.lastname: Yellin
authors.forename: Jolie
authors.initials: J
authors.lastname: Snively
authors.forename: Evan
authors.initials: E
authors.lastname: Hersh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics*; D005123:Eye / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047368:Tumor Burden / Q000187:drug effects; D014820:Vitiligo / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab