Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)
- Conditions
- Advanced or Metastatic Melanoma
- Interventions
- Biological: NivolumabBiological: Ipilimumab
- Registration Number
- NCT01783938
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab
- Detailed Description
In order to evaluate the potential synergistic activity of nivolumab and ipilimumab and also because there may be differences in biology between tumors which are stable or responding to therapy and those that are clinically progressing, this study, CA209064, looked at two sequential combination regimens in which the second agent is administered immediately after a pre-specified duration of therapy with the first agent and not delayed until the time of progression after the first agent. This sequential study design looked at pharmacodynamic changes during treatment with one agent which may predict clinical activity to subsequent treatment with the alternate agent. This was done because it has not been scientifically proven whether or not the order in which nivolumab and ipilimumab are given is clinically important.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 138
- Histologically confirmed unresectable Stage III or IV melanoma
- Treatment-naive or experienced disease recurrence or progression during or after one prior systemic regimen for advanced disease
- Measurable disease by Computed Tomography/Magnetic resonance imaging (CT/MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Known BRAF V600 mutation status or consent to BRAF V600 mutation testing
- Sufficient tumor tissue accessible for baseline and post-treatment biopsies.
- Active central nervous system (CNS) metastases
- Carcinomatous meningitis
- Active, known or suspected autoimmune disease
- Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
- Prior therapy with anti-Programmed Death-1 (PD1), anti-Programmed Death-Ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-CTLA-4 (cytotoxic T lymphocyte antigen 4) antibody
- Prior treatment with other immunotherapies
- Prior therapy with BRAF inhibitor within 6 weeks of enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B: Ipilimumab followed by Nivolumab Nivolumab Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period. Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1. Cohort A: Nivolumab followed by Ipilimumab Ipilimumab Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1. Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period. Cohort A: Nivolumab followed by Ipilimumab Nivolumab Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1. Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period. Cohort B: Ipilimumab followed by Nivolumab Ipilimumab Ipilimumab 3 mg/kg solution intravenously every 3 weeks up to 4 doses in Induction period. Nivolumab 3 mg/kg solution intravenously every 2 weeks up to 6 doses in Induction period and 3 mg/kg solution intravenously every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent in Continuation period for a maximum of 2 years from 1st study treatment in Induction Period 1.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2) From Day 1 to up to Week 25 The percentage of participants with treatment-related grade 3-5 adverse events (AEs) is defined as the number of participants who experienced at least 1 treatment related grade 3 - 5 adverse event (AE) per national cancer institute common terminology criteria for adverse events (NCI CTCAE v4.0, any preferred term) with an onset date after or on first day of Induction Period #1 and not later than discontinuation date from Induction Period #2, divided by the total number of treated participants.
Adverse Event (AE) = any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment.
Treatment-related = having certain, probable, possible, or missing relationship to study drug.
Grade (Gr) 3=Severe Gr 4=Potentially Life-threatening or disabling Gr 5=Death
- Secondary Outcome Measures
Name Time Method Investigator-Assessed Response Rate at Week 25 Week 25 Response rate is defined as the number of participants who have a complete response (CR) or partial response (PR) at Week 25 per modified RECIST 1.1 criteria, with confirmation on the scheduled scan at Week 33 (or any subsequent scan performed at least 4 weeks after the Week 25 scan), divided by the total number of treated participants. Results of the tumor assessment at Week 13 or any unscheduled tumor assessment obtained prior to Week 25, except for baseline/screening tumor assessment, were not considered in the assessment of response rate at Week 25.
Investigator-Assessed Duration of Response (DOR) From week 25 to up to date of disease progression or death (Up to 6 years) Duration of response (DOR) is defined as the time between the Week 25 date of response and the date of objectively documented disease progression as defined by modified RECIST 1.1 criteria or death, whichever occurs first. Median computed using Kaplan-Meier method.
Investigator-Assessed Rate of Progression Week 13 and Week 25 Progression rate at a specific timepoint is defined as the number of participants who have Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at that specific timepoint divided by the total number of treated participants. As specified by modified RECIST 1.1, the evaluation of PD at Week 13 and Week 25 used the baseline tumor assessment as reference. A participant who died without a reported prior progression was considered to have progressed on the date of death. Deaths before or at Week 13 are counted as progression outcome. Confidence interval is based on the Clopper and Pearson method.
Trial Locations
- Locations (10)
University Of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Indiana University Health Melvin And Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University Of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States