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

Non-Small-Cell Lung Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02659059
• Other study ID #: CA209-568
• Status: Completed
• Phase: Phase 2
• Start date: February 15, 2016
• Est. completion date: March 7, 2022

Study information

• Verified date: March 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: March 7, 2022
• Est. primary completion date: June 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

Biological:
• Nivolumab
Specified Dose on Specified Days
• Ipilimumab
Specified Dose on Specified Days

Drug:
• Platinum Doublet Chemotherapy

Locations

Country	Name	City	State
Canada	Local Institution - 0022	Kingston	Ontario
Canada	Local Institution - 0023	Sault Ste Marie	Ontario
Canada	Csss De St-Jerome	St. Jerome	Quebec
United States	Local Institution - 0036	Albuquerque	New Mexico
United States	Lovelace Cancer Care	Albuquerque	New Mexico
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	New Mexico Cancer Care Center	Albuquerque	New Mexico
United States	The Cancer Center at Presbyterian	Albuquerque	New Mexico
United States	Winship Cancer Institute.	Atlanta	Georgia
United States	Johns Hopkins Cancer Center	Baltimore	Maryland
United States	Local Institution - 0029	Boston	Massachusetts
United States	Local Institution - 0030	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Charleston Hematology Oncology Associates, Pa	Charleston	South Carolina
United States	The Ohio State University	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Local Institution - 0015	Lincoln	Nebraska
United States	University Of Louisville Medical Center, Inc., Dba	Louisville	Kentucky
United States	Local Institution - 0010	Mineola	New York
United States	Tennessee Oncology, PLLC - SCRI - PPDS	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Local Institution - 0006	Pittsburgh	Pennsylvania
United States	Cancer Center Of Central Connecticut	Plainville	Connecticut
United States	Sharp Memorial Hospital	San Diego	California
United States	Summit Cancer Care	Savannah	Georgia
United States	Cleveland Clinic Florida	Weston	Florida
United States	Cancer Center Of Kansas	Wichita	Kansas
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose to database lock (Up to 18 months)
Primary	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.	9 weeks after first dose
Primary	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.	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
Primary	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.	From first dose to 30 days post last dose
Primary	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.	From first dose to 30 days post last dose
Secondary	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.	From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Secondary	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.	From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)
Secondary	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.	From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Secondary	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.	From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months)
Secondary	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.	From first dose up to approximately 72 months
Secondary	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.	From first dose up to approximately 59 months
Secondary	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)	From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Secondary	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)	From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Secondary	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)	From first dose up to approximately 72 months
Secondary	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	From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
Secondary	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	From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
Secondary	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	From first dose up to approximately 72 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form