Melanoma
Conditions
Brief summary
The purpose of this study is to determine whether the combination of interleukin-21 (IL-21) and Ipilimumab in subjects with melanoma is safe, and provide preliminary information on the clinical benefits of the combination compared with Ipilimumab alone
Detailed description
Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized
Interventions
BIOLOGICALBMS-982470 (recombinant interleukin-21)
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
BIOLOGICALIpilimumab
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Unresectable Stage III or Stage IV melanoma * Part 1 Dose Escalation: Prior melanoma treatment allowed except for the following: ipilimumab, BMS-982470 (rIL-21), anti-Programmed Death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2 or anti-CD137 * Part 2 Cohort expansion: Prior treatment for melanoma is not allowed, except for adjuvant therapy with interferon alpha or melanoma vaccines which are permitted * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) * Normal liver function tests
Exclusion criteria
* Part 1 Dose escalation: subjects with ≤ 2 brain metastases of stable size, ≥ 4 weeks post-radiation treatment, and off steroids are allowed * Part 2 Cohort expansion: subjects with known or suspected brain metastases and uveal melanoma are excluded * Autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab | Within the first 63 days | Based on the dose-limiting toxicity (DLT) rate |
| Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules | 84 days on treatment | Based on medical review of AE reports and the results of vital sign measurements, physical examinations, medical history, and clinical laboratory tests |
Secondary
| Measure | Time frame |
|---|---|
| The time of maximum observed serum concentration (Tmax) of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Serum half-life (T-HALF) of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Apparent total body clearance (CLT) of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Efficacy of BMS-982470 in combination with Ipilimumab as measured by objective response | Baseline (Day 1), End of Treatment (EOT) [3 weeks after last dose of Ipilimumab], 3 and 6 months Follow-up |
| Area under the serum concentration-time curve from time zero to the last quantifiable concentration [AUC(0-T)] of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| The maximum observed serum concentration (Cmax) of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab | 1 time point each 3-week Cycle |
| Apparent volume of distribution at steady state (Vss) of BMS-982470 and Ipilimumab | 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 |
| Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies | Up to 6 months following last dose |
Countries
Puerto Rico, United States
Outcome results
None listed