Back to resultsStudy of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)
Primary Purpose
Advanced or Metastatic Melanoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced or Metastatic Melanoma
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- H. Lee Moffitt Cancer Center & Research Institute
- Indiana University Health Melvin And Bren Simon Cancer Center
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute
- Dana-Farber Cancer Institute
- Massachusetts General Hospital
- Lehigh Valley Health Network
- University Of Pennsylvania
- Vanderbilt-Ingram Cancer Center
- Vanderbilt-Ingram Cancer Center
- University Of Virginia Health System
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A: Nivolumab followed by Ipilimumab
Cohort B: Ipilimumab followed by Nivolumab
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2)
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
Investigator-Assessed Response Rate at 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)
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01783938
Brief Title
Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)
Official Title
An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
April 30, 2013 (Actual)
Primary Completion Date
April 3, 2015 (Actual)
Study Completion Date
August 12, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced or Metastatic Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: Nivolumab followed by Ipilimumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B: Ipilimumab followed by Nivolumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2)
Description
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
Time Frame
From Day 1 to up to Week 25
Secondary Outcome Measure Information:
Title
Investigator-Assessed Response Rate at Week 25
Description
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.
Time Frame
Week 25
Title
Investigator-Assessed Duration of Response (DOR)
Description
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.
Time Frame
From week 25 to up to date of disease progression or death (Up to 6 years)
Title
Investigator-Assessed Rate of Progression
Description
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.
Time Frame
Week 13 and Week 25
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Indiana University Health Melvin And Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Lehigh Valley Health Network
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6307
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University Of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32303612
Citation
Yoshida T, Ichikawa J, Giuroiu I, Laino AS, Hao Y, Krogsgaard M, Vassallo M, Woods DM, Stephen Hodi F, Weber J. C reactive protein impairs adaptive immunity in immune cells of patients with melanoma. J Immunother Cancer. 2020 Apr;8(1):e000234. doi: 10.1136/jitc-2019-000234. Erratum In: J Immunother Cancer. 2020 May;8(1):
Results Reference
derived
PubMed Identifier
27269740
Citation
Weber JS, Gibney G, Sullivan RJ, Sosman JA, Slingluff CL Jr, Lawrence DP, Logan TF, Schuchter LM, Nair S, Fecher L, Buchbinder EI, Berghorn E, Ruisi M, Kong G, Jiang J, Horak C, Hodi FS. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Lancet Oncol. 2016 Jul;17(7):943-955. doi: 10.1016/S1470-2045(16)30126-7. Epub 2016 Jun 4. Erratum In: Lancet Oncol. 2016 Jul;17 (7):e270.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource
Learn more about this trial
Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)
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