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

2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 36 Linguagem: Inglês

10.1200/jco.2008.16.1927

1527-7755

Jeffrey S. Weber, Steven O’Day, Walter J. Urba, John D. Powderly, Geoff Nichol, Michael Yellin, Jolie Snively, Evan M. Hersh,

vaccines and immunoinformatics approaches

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.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.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.Ipilimumab has activity in patients with metastatic melanoma. Late responses were observed in patients with prolonged SD.