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

NCT ID: NCT01783938

Last Updated: 2021-08-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2020-08-12

Brief Summary

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

Detailed Description

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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.

Conditions

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Advanced or Metastatic Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Interventions

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Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Other Intervention Names

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BMS-936558 Yervoy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

Indiana University Health Melvin And Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

University Of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

University Of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 32303612 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27269740 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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CA209-064

Identifier Type: -

Identifier Source: org_study_id

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