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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)

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: NCT02659059
Recruitment Status : Active, not recruiting
First Posted : January 20, 2016
Results First Posted : July 22, 2021
Last Update Posted : April 18, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Non-Small-Cell Lung Cancer Biological: Nivolumab Biological: Ipilimumab Drug: Platinum Doublet Chemotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 324 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : February 15, 2016
Actual Primary Completion Date : June 22, 2018
Estimated Study Completion Date : April 20, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Part 1 up to 18 months and Part 2 up to 24 months ]
    Overall survival (OS) was defined as the time from date of first treatment to the date of death for part 1 and part 2. A participant who has not died will be censored at the last known date alive.

  2. Progression Free Survival (PFS) - Part 1 [ Time Frame: Up to 18 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.

  3. Progression Free Survival (PFS) - Part 2 [ Time Frame: Up to 24 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.

  4. Objective Response Rate (ORR) - Part 1 [ Time Frame: Up to 18 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.

  5. Objective Response Rate (ORR) - Part 2 [ Time Frame: Up to 24 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.

  6. Overall Survival (OS) by PD-L1 Expression Levels - Part 1 [ Time Frame: Up to 18 months ]
    Overall survival (OS) by PD-L1 expression levels was defined as the time from date of first treatment to the date of death. A participant who has not died will be censored at the last known date alive.

  7. Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1 [ Time Frame: Up to 18 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.

  8. Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1 [ Time Frame: Up to 18 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.

  9. Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1 [ Time Frame: Up to 18 months ]
    Overall survival (OS) by tumor mutational burden (TMB) using DNA derived from tumor specimens. High TMB is >= 10 mutations per megabase and Low TMB is < 10 mutations per megabase.

  10. Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1 [ Time Frame: Up to 18 months ]
    Progression free survival (PFS) by tumor mutational burden (TMB) using DNA derived from tumor specimens. High TMB is >= 10 mutations per megabase and Low TMB is < 10 mutations per megabase.

  11. Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1 [ Time Frame: Up to 18 months ]
    Objective response rate (ORR) by tumor mutational burden (TMB) using DNA derived from tumor specimens. High TMB is >= 10 mutations per megabase and Low TMB is < 10 mutations per megabase.



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 Bristol-Myers Squibb (BMS) Clinical Trial participation, please visit www.BMSStudyConnect.com

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 could apply


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): NCT02659059


Locations
Show Show 32 study locations
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] January 11, 2018
Statistical Analysis Plan  [PDF] April 25, 2019

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: NCT02659059    
Other Study ID Numbers: CA209-568
First Posted: January 20, 2016    Key Record Dates
Results First Posted: July 22, 2021
Last Update Posted: April 18, 2022
Last Verified: April 2022

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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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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Cisplatin
Carboplatin
Nivolumab
Pemetrexed
Ipilimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors