An Open-Label Pharmacokinetic and Safety Study of MDX-010 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
Group A: Six to 12 subjects will be treated with transfectoma-derived MDX-010 at 2.8 or 5
mg/kg/dose, or with hybridoma-derived MDX-010 at 3 mg/kg/dose administered on Days 1, 57,
and 85. The 2.8, 3, and 5 mg/kg dosage cohorts may be initiated concurrently. Additionally,
6 subjects per cohort will receive single doses of transfectoma-derived MDX-010 at 7.5, 10,
15, and 20 mg/kg.
Dose escalation from the 5 mg/kg cohort to the 7.5 mg/kg cohort will depend on the safety
profile following a single dose of 5 mg/kg. Once all subjects are enrolled in the 5 mg/kg
cohort and 4 weeks have elapsed since the sixth subject in the cohort has received the first
infusion, dose escalation to the 7.5 mg/kg cohort may occur if ≤1 DLT has occurred in the 5
mg/kg cohort. Dose escalation to the 10 mg/kg cohort may occur 4 weeks after the sixth
subject in the 7.5 mg/kg/dose cohort has received the first infusion (with ≤1 DLT). Dose
escalation to the 15 and 20 mg/kg cohorts may occur 4 weeks after the sixth subject in the
previous cohort has received the first infusion (with ≤1 DLT). Up to six additional subjects
may be enrolled in the MTD dose cohort or in the 20 mg/kg dose cohort if MTD is not
Group B: If single-dose administration of MDX-010 at 10 mg/kg is well tolerated (≤1 DLT in
the cohort in Group A), then an additional 12 to 20 subjects will be enrolled and treated
with MDX-010 at 10 mg/kg/dose administered on Days 1, 22, 43, and 64.
Subjects who respond to therapy will be followed until disease progression or a maximum of
approximately 1 year. Subjects with a response of SD ≥ 3 months, PR, or CR to their initial
treatment cycle who subsequently relapse may be eligible for retreatment with the same
regimen or an alternate regimen considered to be more effective at the time of retreatment.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety and pharmacokinetic profile of single and multiple doses of MDX-010.
up to approximately 1 year
United States: Institutional Review Board
|Arizona Cancer Center||Tucson, Arizona 85724|
|USC/Norris Comprehensive Cancer Center||Los Angeles, California 90033-0800|
|Providence Portland Medical Center||Portland, Oregon 97213-3635|
|Piedmont Oncology Specialists||Charlotte, North Carolina 28207|