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

July 22, 2021 updated by: Bristol-Myers Squibb

An Open-Label, Randomized, Phase 2 Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma

The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

138

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health Melvin and Bren Simon Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • 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
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Health Network
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37232-6307
        • Vanderbilt-Ingram Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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 Names:
  • BMS-936558
Biological: Ipilimumab
Other Names:
  • 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 Names:
  • BMS-936558
Biological: Ipilimumab
Other Names:
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From Day 1 to up to Week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 25
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.
From week 25 to up to date of disease progression or death (Up to 6 years)
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.
Week 13 and Week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2013

Primary Completion (Actual)

April 3, 2015

Study Completion (Actual)

August 12, 2020

Study Registration Dates

First Submitted

February 1, 2013

First Submitted That Met QC Criteria

February 1, 2013

First Posted (Estimate)

February 5, 2013

Study Record Updates

Last Update Posted (Actual)

August 13, 2021

Last Update Submitted That Met QC Criteria

July 22, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-064

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced or Metastatic Melanoma

Clinical Trials on Nivolumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe