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Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01783938
Recruitment Status : Completed
First Posted : February 5, 2013
Results First Posted : April 11, 2016
Last Update Posted : August 13, 2021
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Melanoma Biological: Nivolumab Biological: Ipilimumab Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma
Actual Study Start Date : April 30, 2013
Actual Primary Completion Date : April 3, 2015
Actual Study Completion Date : August 12, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A: Nivolumab followed by 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.

 Biological: Nivolumab
Other Name: BMS-936558

Biological: Ipilimumab
Other Name: Yervoy
Experimental: Cohort B: Ipilimumab followed by 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.

 Biological: Nivolumab
Other Name: BMS-936558

Biological: Ipilimumab
Other Name: Yervoy


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Treatment-Related Grade 3-5 Adverse Events (AEs) During the Induction Period (Period 1 and 2) [ Time Frame: 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 :
  1. Investigator-Assessed Response Rate at Week 25 [ Time Frame: 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.

  2. Investigator-Assessed Duration of Response (DOR) [ Time Frame: 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.

  3. Investigator-Assessed Rate of Progression [ Time Frame: 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01783938


Locations
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United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University Health Melvin And Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18103
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6307
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
University Of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] March 28, 2013
Statistical Analysis Plan  [PDF] March 12, 2014

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01783938    
Other Study ID Numbers: CA209-064
First Posted: February 5, 2013    Key Record Dates
Results First Posted: April 11, 2016
Last Update Posted: August 13, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
 Nevi and Melanomas
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action