Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma

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.