PURPOSE: 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.
PATIENTS AND 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.
CONCLUSION: Ipilimumab has activity in patients with metastatic melanoma. Late 
responses were observed in patients with prolonged SD.