TY - JOUR
T1 - Phase I/II study of ipilimumab for patients with metastatic melanoma
AU - Weber, Jeffrey S.
AU - O'Day, Steven
AU - Urba, Walter
AU - Powderly, John
AU - Nichol, Geoff
AU - Yellin, Michael
AU - Snively, Jolie
AU - Hersh, Evan
PY - 2008/12/20
Y1 - 2008/12/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2008.16.1927
DO - 10.1200/JCO.2008.16.1927
M3 - Article
C2 - 19018089
AN - SCOPUS:58049202334
SN - 0732-183X
VL - 26
SP - 5950
EP - 5956
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -