Nivolumab in Combination With Ipilimumab (Part 1); Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (CheckMate 568)

March 7, 2023 updated by: Bristol-Myers Squibb

A Study of Nivolumab in Combination With Ipilimumab (Part 1); and Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)

The purpose of part 1 of this study is to determine the objective response rate (ORR) in stage IV NSCLC subjects treated with nivolumab in combination with ipilimumab as first line therapy.

The purpose of part 2 of this study is to determine the safety and tolerability of nivolumab and ipilimumab combined with a short course of chemotherapy in first line stage IV NSCLC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

324

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

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Local Institution - 0022
      • Sault Ste Marie, Ontario, Canada, P6B 0A8
        • Local Institution - 0023
    • Quebec
      • St. Jerome, Quebec, Canada, J7Z 5T3
        • Csss De St-Jerome
  • United States
    • California
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
    • Connecticut
      • Plainville, Connecticut, United States, 06062
        • Cancer Center of Central Connecticut
    • Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute.
      • Savannah, Georgia, United States, 31405
        • Summit Cancer Care
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University Of Louisville Medical Center, Inc., Dba
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02114-2621
        • Local Institution - 0029
      • Boston, Massachusetts, United States, 02114-2621
        • Local Institution - 0030
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Local Institution - 0015
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • New Mexico Cancer Care Alliance
      • Albuquerque, New Mexico, United States, 87131
        • Lovelace Cancer Care
      • Albuquerque, New Mexico, United States, 87131
        • New Mexico Cancer Care Center
      • Albuquerque, New Mexico, United States, 87131
        • The Cancer Center at Presbyterian
      • Albuquerque, New Mexico, United States, 87106
        • Local Institution - 0036
    • New York
      • Mineola, New York, United States, 11501
        • Local Institution - 0010
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Oncology Specialists
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2412
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • Local Institution - 0006
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Charleston Hematology Oncology Associates, PA
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6307
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC - SCRI - PPDS

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

Inclusion Criteria:

  • Men and Women ≥ 18 years of age
  • Diagnosed with stage IV Non-Small Cell Lung Cancer
  • Diagnosed with recurrent stage IIIB non-small cell lung cancer and failed previous concurrent chemoradiation with no further curative options.

Exclusion Criteria:

  • Subjects with untreated CNS metastases are excluded.
  • Subjects with carcinomatous meningitis
  • Subjects with an active, known or suspected autoimmune disease.
  • Subjects with a condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
  • Women who are pregnant, plan to become pregnant, and/or breastfeed during the study.

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nivolumab+Ipilimumab

Part 1

Specified Dose on Specified Days
Biological: Nivolumab
Specified Dose on Specified Days
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified Dose on Specified Days
Other Names:
  • BMS-734016
  • Yervoy
Experimental: Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy

Part 2

Specified Dose on Specified Days
Biological: Nivolumab
Specified Dose on Specified Days
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified Dose on Specified Days
Other Names:
  • BMS-734016
  • Yervoy
Drug: Platinum Doublet Chemotherapy
Other Names:
  • Carboplatin + Paclitaxel
  • Cisplatin + pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1
Time Frame: From first dose to database lock (Up to 18 months)
Objective response rate (ORR) in PD-L1 positive (PD-L1 ≥1%) and PD-L1 negative (PD-L1 <1%) participants was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.
From first dose to database lock (Up to 18 months)
Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2
Time Frame: 9 weeks after first dose

Dose limiting toxicities (DLTs) were defined as any of the items listed below.

  1. Any Grade 2 drug-related uveitis or eye pain that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment.
  2. Any Grade 2 drug-related pneumonitis or interstitial lung disease that does not resolve to dose delay and systemic steroids in 14 days.
  3. Any Grade 3 non-skin drug-related adverse event with the exception of laboratory abnormalities that cannot be alleviated or controlled by appropriate care within 14 days.
  4. Any Grade 4 drug-related adverse event including laboratory abnormalities except Grade 4 leukopenia or neutropenia lasting < 14 days and asymptomatic amylase/lipase elevation.
  5. Drug-related hepatic function laboratory abnormalities.
9 weeks after first dose
Number of Participants With Adverse Events (AEs) - Part 2
Time Frame: Deaths are from first dose to database lock (Up to 24 months). AEs and SAEs are from first dose to 30 days post last dose
Number of participants with adverse events (AEs) including serious adverse events (SAEs) and deaths graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
Deaths are from first dose to database lock (Up to 24 months). AEs and SAEs are from first dose to 30 days post last dose
Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2
Time Frame: From first dose to 30 days post last dose
Number of participant with specific liver laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
From first dose to 30 days post last dose
Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2
Time Frame: From first dose to 30 days post last dose
Number of participants with specific thyroid laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
From first dose to 30 days post last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) - Part 1
Time Frame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Overall survival (OS) was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.
From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Overall Survival (OS) - Part 2
Time Frame: From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)
Overall survival (OS) was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.
From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)
Progression Free Survival (PFS) - Part 1
Time Frame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Progression Free Survival (PFS) - Part 2
Time Frame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months)
Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by investigator (per RECIST 1.1), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months)
Objective Response Rate (ORR) - Part 1
Time Frame: From first dose up to approximately 72 months

Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From first dose up to approximately 72 months
Objective Response Rate (ORR) - Part 2
Time Frame: From first dose up to approximately 59 months

Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on investigator assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From first dose up to approximately 59 months
Overall Survival (OS) by PD-L1 Expression Levels - Part 1
Time Frame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

Overall survival (OS) by PD-L1 expression levels was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)
From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1
Time Frame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)

Progression Free Survival (PFS) by PD-L1 expression levels was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)
From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1
Time Frame: From first dose up to approximately 72 months

Objective response rate (ORR) by PD-L1 expression levels was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)
From first dose up to approximately 72 months
Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1
Time Frame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

Overall survival (OS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.

High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase
From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1
Time Frame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)

Progression Free Survival (PFS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase
From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1
Time Frame: From first dose up to approximately 72 months

Objective response rate (ORR) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase
From first dose up to approximately 72 months

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)

February 15, 2016

Primary Completion (Actual)

June 22, 2018

Study Completion (Actual)

March 7, 2022

Study Registration Dates

First Submitted

January 15, 2016

First Submitted That Met QC Criteria

January 15, 2016

First Posted (Estimate)

January 20, 2016

Study Record Updates

Last Update Posted (Actual)

April 5, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-568

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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