An Exploratory Study of the Effects of Nivolumab Combined With Ipilimumab in Patients With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) (CheckMate 592)

April 22, 2024 updated by: Bristol-Myers Squibb

An Exploratory Study of the Biologic Effects and Biomarkers of Nivolumab in Combination With Ipilimumab in Subjects With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to explore the possible links between participant characteristics and their cancer, with how effective the combination of nivolumab with ipilimumab is, in participants with Stage IV or recurrent Non-Small Cell Lung Cancer (NSCLC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

230

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

  • Belgium
      • Gent, Belgium, 9000
        • Local Institution - 0018
      • Gent, Belgium, 9000
        • Local Institution - 0028
      • Liege, Belgium, 4000
        • Local Institution - 0027
      • Sint-Niklaas, Belgium, 9100
        • Local Institution - 0016
    • Hainaut
      • La Louvière, Hainaut, Belgium, 7100
        • Local Institution - 0017
  • France
      • Paris Cedex 5, France, 75248
        • Local Institution - 0036
      • Pierre Benite, France, 69495
        • Local Institution - 0033
      • Strasbourg Cedex, France, 67091
        • Local Institution - 0034
      • Toulon, France, 83000
        • Local Institution - 0039
  • Germany
      • Essen, Germany, 45136
        • Local Institution - 0015
      • Immenstadt, Germany, 87509
        • Local Institution - 0014
      • Loewenstein, Germany, 74245
        • Local Institution - 0013
      • Stuttgart, Germany, 70174
        • Local Institution - 0012
  • Italy
      • Bergamo, Italy, 24127
        • Local Institution - 0023
      • Catania, Italy, 95123
        • Local Institution - 0025
      • Parma, Italy, 43100
        • Local Institution - 0026
      • Perugia, Italy, 06129
        • Local Institution - 0024
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Local Institution - 0021
      • Nijmegen, Netherlands, 6525 GA
        • Local Institution - 0022
  • Romania
      • Craiova, Romania, 200542
        • Local Institution - 0010
    • Cluj
      • Cluj-Napoca, Cluj, Romania, 400015
        • Local Institution - 0011
  • Spain
      • Barcelona, Spain, 08908
        • Local Institution - 0031
      • Madrid, Spain, 28041
        • Local Institution - 0029
      • Madrid, Spain, 28046
        • Local Institution - 0030
      • Sevilla, Spain, 41009
        • Local Institution - 0032
  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Local Institution - 0006
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Local Institution - 0001
    • Florida
      • Jacksonville, Florida, United States, 32256
        • Local Institution - 0005
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Local Institution - 0009
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Local Institution - 0003
    • New York
      • Bronx, New York, United States, 10461
        • Local Institution - 0038
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Local Institution - 0002
      • Cleveland, Ohio, United States, 44195
        • Local Institution - 0008
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • Local Institution - 0007
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Local Institution - 0004

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

Description

Inclusion Criteria:

  • Histologically confirmed, stage IV or recurrent non-small cell lung cancer with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease
  • Measurable disease by CT or MRI
  • Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work

Exclusion Criteria:

  • Participants with untreated central nervous system metastases
  • Participants with active, known or suspected autoimmune disease
  • Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)

Other protocol defined inclusion/exclusion criteria apply

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination therapy
Nivolumab + Ipilimumab
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (TMB Cut-point = 16 Mutations/MB)
Time Frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to <10 mm.

Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.

CR+PR, confidence interval based on the Clopper and Pearson method.
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)
Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (Blood TMB Cut-point = 21-mutations/MB)
Time Frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to <10 mm.

Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.

CR+PR, confidence interval based on the Clopper and Pearson method.
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)
Objective Response Rate (ORR) Per Investigator by Tissue TMB Within PD-L1 Subgroup (Tissue TMB Cut-point = 10-mutations/MB)
Time Frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to <10 mm.

Tissue tumor mutational burden (tTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in tumor tissue samples.

CR+PR, confidence interval based on the Clopper and Pearson method.
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) for Study Part 2
Time Frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)

An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment.

An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Number of Participants With Serious Adverse Events (SAEs) for Study Part 2
Time Frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
A Serious Adverse Event (SAE) results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), or requires inpatient hospitalization or causes prolongation of existing hospitalization.
From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Number of Participants With Select Adverse Events (AEs) for Study Part 2
Time Frame: From first dose to 30 days after last dosing date (up to approximately 27 months)

An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment.

An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
From first dose to 30 days after last dosing date (up to approximately 27 months)
Objective Response Rate (ORR) for All Treated Participants by Investigator Per RECIST 1.1
Time Frame: From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to <10 mm.

CR+PR, confidence interval based on the Clopper and Pearson method.
From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)
Disease Control Rate (DCR) for Part 1
Time Frame: From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)

Disease control rate (DCR) is the percent of treated participants with a best overall response of a complete response (CR), partial response (PR), or stable disease (SD), assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in short axis to <10 mm of any pathological lymph nodes (target or non-target). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking smallest sum diameters as reference. PD is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also demonstrate an absolute increase of at least 5 mm. (one or more new lesions is also considered progression). CR+PR, confidence interval based on the Clopper and Pearson method.
From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)
Duration of Response (DOR) for Part 1
Time Frame: From first dose to the date of the first documented tumor progression or death due to any cause (Up to approximately 67 months)

DOR is the time between first confirmed response (Complete/Partial Response) and first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who don't progress or die are censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy without prior reported progression were censored at the last evaluable tumor assessment prior to or on the date of subsequent anti-cancer therapy.

PR is at least 30% decrease in the sum of diameters of target lesions, using baseline sum diameters as reference. CR is disappearance of all target lesions and reduction in short axis to <10 mm of any pathological lymph nodes (target or non-target). Progressive Disease (PD) is at least 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also show an overall increase of > 5 mm. (one or more new lesions is also progression). Median computed using Kaplan-Meier method.
From first dose to the date of the first documented tumor progression or death due to any cause (Up to approximately 67 months)
Time to Response (TTR) for Part 1
Time Frame: From first dose to the time the criteria for Complete Response/Partial Response are first met (Up to approximately 67 months)

TTR is the time taken from first dosing date to the time the criteria for Complete Response (CR)/Partial Response (PR) are first met.

Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
From first dose to the time the criteria for Complete Response/Partial Response are first met (Up to approximately 67 months)
Progression Free Survival (PFS)
Time Frame: From first dose to the date of the first documented tumor progression or death due to any causes (Assessed up to approximately 67 months)

PFS is defined as the time from first dosing date to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause.

Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on the date of initiation of subsequent anti-cancer therapy.

Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as reference. The sum must also show an overall increase of > 5 mm. (one or more new lesions is also progression).

Median calculated using Kaplan-Meier estimates.
From first dose to the date of the first documented tumor progression or death due to any causes (Assessed up to approximately 67 months)
Overall Survival (OS)
Time Frame: From first dose to the date of death (Assessed up to approximately 67 months)

OS is defined as the time from first dosing date to the date of death. If a participant didn't die, OS will be censored on the last date the participant was known to be alive.

Median based on Kaplan-Meier estimates.
From first dose to the date of death (Assessed up to approximately 67 months)

Collaborators and Investigators

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

Sponsor

Bristol-Myers Squibb

Collaborators

Yale University

Investigators

  • Study Director: Bristol-Myers Squibb, 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.

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)

March 29, 2017

Primary Completion (Actual)

February 17, 2022

Study Completion (Actual)

April 24, 2023

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

December 22, 2016

First Posted (Estimated)

December 23, 2016

Study Record Updates

Last Update Posted (Actual)

May 20, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-592
  • 2018-000462-11 (EudraCT Number)

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.

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