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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)

Primary Purpose

Non-Small-Cell Lung Cancer

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Nivolumab

Ipilimumab

Platinum Doublet Chemotherapy

About this trial

This is an interventional treatment trial for Non-Small-Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Nivolumab+Ipilimumab

Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy

Arm Description

Part 1 Specified Dose on Specified Days

Part 2 Specified Dose on Specified Days

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1

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.

Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2

Dose limiting toxicities (DLTs) were defined as any of the items listed below. 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. Any Grade 2 drug-related pneumonitis or interstitial lung disease that does not resolve to dose delay and systemic steroids in 14 days. 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. Any Grade 4 drug-related adverse event including laboratory abnormalities except Grade 4 leukopenia or neutropenia lasting < 14 days and asymptomatic amylase/lipase elevation. Drug-related hepatic function laboratory abnormalities.

Number of Participants With Adverse Events (AEs) - Part 2

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.

Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2

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.

Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2

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

Overall Survival (OS) - Part 1

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.

Overall Survival (OS) - Part 2

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.

Progression Free Survival (PFS) - Part 1

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.

Progression Free Survival (PFS) - Part 2

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.

Objective Response Rate (ORR) - Part 1

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.

Objective Response Rate (ORR) - Part 2

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.

Overall Survival (OS) by PD-L1 Expression Levels - Part 1

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)

Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1

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)

Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1

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)

Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1

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

Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1

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

Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1

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

Full Information

NCT ID

NCT02659059

First Posted

January 15, 2016

Last Updated

March 7, 2023

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT02659059

Brief Title

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

Acronym

CheckMate 568

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

February 15, 2016 (Actual)

Primary Completion Date

June 22, 2018 (Actual)

Study Completion Date

March 7, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small-Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

324 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nivolumab+Ipilimumab

Arm Type

Experimental

Arm Description

Part 1 Specified Dose on Specified Days

Arm Title

Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy

Arm Type

Experimental

Arm Description

Part 2 Specified Dose on Specified Days

Intervention Type

Biological

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

BMS-936558, Opdivo

Intervention Description

Specified Dose on Specified Days

Intervention Type

Biological

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

BMS-734016, Yervoy

Intervention Description

Specified Dose on Specified Days

Intervention Type

Drug

Intervention Name(s)

Platinum Doublet Chemotherapy

Other Intervention Name(s)

Carboplatin + Paclitaxel, Cisplatin + pemetrexed

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1

Description

Time Frame

From first dose to database lock (Up to 18 months)

Title

Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2

Description

Time Frame

9 weeks after first dose

Title

Number of Participants With Adverse Events (AEs) - Part 2

Description

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

Title

Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2

Description

Time Frame

From first dose to 30 days post last dose

Title

Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2

Description

Time Frame

From first dose to 30 days post last dose

Secondary Outcome Measure Information:

Title

Overall Survival (OS) - Part 1

Description

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.

Time Frame

From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

Title

Overall Survival (OS) - Part 2

Description

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.

Time Frame

From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)

Title

Progression Free Survival (PFS) - Part 1

Description

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)

Title

Progression Free Survival (PFS) - Part 2

Description

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)

Title

Objective Response Rate (ORR) - Part 1

Description

Time Frame

From first dose up to approximately 72 months

Title

Objective Response Rate (ORR) - Part 2

Description

Time Frame

From first dose up to approximately 59 months

Title

Overall Survival (OS) by PD-L1 Expression Levels - Part 1

Description

Time Frame

From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

Title

Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1

Description

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)

Title

Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1

Description

Time Frame

From first dose up to approximately 72 months

Title

Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1

Description

Time Frame

From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

Title

Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1

Description

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)

Title

Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1

Description

Time Frame

From first dose up to approximately 72 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Sharp Memorial Hospital

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

Cancer Center Of Central Connecticut

City

Plainville

State/Province

Connecticut

ZIP/Postal Code

06062

Country

United States

Facility Name

Cleveland Clinic Florida

City

Weston

State/Province

Florida

ZIP/Postal Code

33331

Country

United States

Facility Name

Winship Cancer Institute.

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Summit Cancer Care

City

Savannah

State/Province

Georgia

ZIP/Postal Code

31405

Country

United States

Facility Name

Cancer Center Of Kansas

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67214

Country

United States

Facility Name

University Of Louisville Medical Center, Inc., Dba

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Johns Hopkins Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Local Institution - 0029

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114-2621

Country

United States

Facility Name

Local Institution - 0030

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114-2621

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Henry Ford Health System

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Local Institution - 0015

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68506

Country

United States

Facility Name

Hackensack University Medical Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Local Institution - 0036

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87106

Country

United States

Facility Name

Lovelace Cancer Care

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

New Mexico Cancer Care Alliance

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

New Mexico Cancer Care Center

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

The Cancer Center at Presbyterian

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

Local Institution - 0010

City

Mineola

State/Province

New York

ZIP/Postal Code

11501

Country

United States

Facility Name

Memorial Sloan Kettering Nassau

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Duke University

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Novant Health Oncology Specialists

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Facility Name

The Ohio State University

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Fox Chase Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111-2412

Country

United States

Facility Name

Local Institution - 0006

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15212

Country

United States

Facility Name

Charleston Hematology Oncology Associates, Pa

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29414

Country

United States

Facility Name

Tennessee Oncology, PLLC - SCRI - PPDS

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-6307

Country

United States

Facility Name

Local Institution - 0022

City

Kingston

State/Province

Ontario

ZIP/Postal Code

K7L 2V7

Country

Canada

Facility Name

Local Institution - 0023

City

Sault Ste Marie

State/Province

Ontario

ZIP/Postal Code

P6B 0A8

Country

Canada

Facility Name

Csss De St-Jerome

City

St. Jerome

State/Province

Quebec

ZIP/Postal Code

J7Z 5T3

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

30785829

Citation

Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, Brahmer J, Rabinowitz I, Reddy PS, Chesney J, Orcutt J, Spigel DR, Reck M, O'Byrne KJ, Paz-Ares L, Hu W, Zerba K, Li X, Lestini B, Geese WJ, Szustakowski JD, Green G, Chang H, Ramalingam SS. First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J Clin Oncol. 2019 Apr 20;37(12):992-1000. doi: 10.1200/JCO.18.01042. Epub 2019 Feb 20.

Results Reference

derived

Links:

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

BMS Clinical Trial Information

URL

https://www.bmsstudyconnect.com/s/US/English/USenHome

Description

BMS Clinical Trial Patient Recruiting

URL

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

Description

FDA Safety Alerts and Recalls

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

Investigator Inquiry Form

Learn more about this trial

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

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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)

Non-Small-Cell Lung Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial