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.
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 melanomapatients. 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.
Authors: Jianda Yuan; Matthew Adamow; Brian A Ginsberg; Teresa S Rasalan; Erika Ritter; Humilidad F Gallardo; Yinyan Xu; Evelina Pogoriler; Stephanie L Terzulli; Deborah Kuk; Katherine S Panageas; Gerd Ritter; Mario Sznol; Ruth Halaban; Achim A Jungbluth; James P Allison; Lloyd J Old; Jedd D Wolchok; Sacha Gnjatic Journal: Proc Natl Acad Sci U S A Date: 2011-09-20 Impact factor: 11.205
Authors: Brian A Ginsberg; Humilidad F Gallardo; Teresa S Rasalan; Matthew Adamow; Zhenyu Mu; Sapna Tandon; Barrett B Bewkes; Ruth-Ann Roman; Paul B Chapman; Gary K Schwartz; Richard D Carvajal; Katherine S Panageas; Stephanie L Terzulli; Alan N Houghton; Jianda D Yuan; Jedd D Wolchok Journal: Clin Cancer Res Date: 2010-07-20 Impact factor: 12.531
Authors: Peter A Prieto; James C Yang; Richard M Sherry; Marybeth S Hughes; Udai S Kammula; Donald E White; Catherine L Levy; Steven A Rosenberg; Giao Q Phan Journal: Clin Cancer Res Date: 2012-01-23 Impact factor: 12.531
Authors: Xiaosong Li; Mark F Naylor; Henry Le; Robert E Nordquist; T Kent Teague; C Anthony Howard; Cynthia Murray; Wei R Chen Journal: Cancer Biol Ther Date: 2010-12-01 Impact factor: 4.742