Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma

A Phase I Dose Escalation Study of BMS-982470 (Recombinant Interleukin 21, rIL-21) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Melanoma

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

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: BMS-982470 (recombinant interleukin-21); Biological: BMS-982470 (recombinant interleukin-21); Biological: BMS-982470 (recombinant interleukin-21); Biological: BMS-982470 (recombinant interleukin-21); Biological: Ipilimumab; Biological: Ipilimumab; Biological: Ipilimumab

Detailed Description

Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Local Institution
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Oncology Research Associates, Pllc D/B/A
  • California
    • Los Angeles, California, United States, 90095
      • Ucla Hematology/Oncology.
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Inst, Inc
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville Medical Center, Inc., Dba
  • Oregon
    • Portland, Oregon, United States, 97213
      • Portland Providence Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Can Cnt
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab; Dose Escalation	Biological: BMS-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; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response; Biological: Ipilimumab; Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®
Experimental: Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab; Dose Escalation	Biological: BMS-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; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response; Biological: Ipilimumab; Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®
Experimental: Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab; Cohort Expansion	Biological: BMS-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; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response; Biological: Ipilimumab; Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®
Experimental: Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab; Cohort Expansion	Biological: BMS-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; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response; Biological: BMS-982470 (recombinant interleukin-21); Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response; Biological: Ipilimumab; Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®
Active Comparator: Part 2 - Arm 3: Ipilimumab monotherapy; Cohort Expansion	Biological: Ipilimumab; Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®; Biological: Ipilimumab; Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response; Other Names: Yervoy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab	Based on the dose-limiting toxicity (DLT) rate	Within the first 63 days
Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules	Based on medical review of AE reports and the results of vital sign measurements, physical examinations, medical history, and clinical laboratory tests	84 days on treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: December 7, 2011
• First Submitted That Met QC Criteria: December 7, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Estimate): August 29, 2014
• Last Update Submitted That Met QC Criteria: August 28, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: CA220-007