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
- Conditions
- Non-Small-Cell Lung Cancer
- Interventions
- Registration Number
- NCT02659059
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 324
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nivolumab+Ipilimumab Nivolumab Part 1 Specified Dose on Specified Days Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy Nivolumab Part 2 Specified Dose on Specified Days Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy Ipilimumab Part 2 Specified Dose on Specified Days Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy Platinum Doublet Chemotherapy Part 2 Specified Dose on Specified Days Nivolumab+Ipilimumab Ipilimumab Part 1 Specified Dose on Specified Days
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) - Part 2 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.
Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2 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.
Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1 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.
Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2 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.Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2 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
Name Time Method Progression Free Survival (PFS) - Part 2 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.
Objective Response Rate (ORR) - Part 1 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.Objective Response Rate (ORR) - Part 2 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.Overall Survival (OS) - Part 2 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.
Progression Free Survival (PFS) - Part 1 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.
Overall Survival (OS) by PD-L1 Expression Levels - Part 1 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)Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1 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 megabaseOverall Survival (OS) - Part 1 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.
Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1 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)Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1 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 megabaseObjective Response Rate (ORR) by PD-L1 Expression Levels-Part 1 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)Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1 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
Trial Locations
- Locations (32)
Local Institution - 0010
🇺🇸Mineola, New York, United States
Local Institution - 0022
🇨🇦Kingston, Ontario, Canada
Local Institution - 0015
🇺🇸Lincoln, Nebraska, United States
Johns Hopkins Cancer Center
🇺🇸Baltimore, Maryland, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Cancer Center Of Central Connecticut
🇺🇸Plainville, Connecticut, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Csss De St-Jerome
🇨🇦St. Jerome, Quebec, Canada
Local Institution - 0023
🇨🇦Sault Ste Marie, Ontario, Canada
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Duke University
🇺🇸Durham, North Carolina, United States
Tennessee Oncology, PLLC - SCRI - PPDS
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Winship Cancer Institute.
🇺🇸Atlanta, Georgia, United States
Summit Cancer Care
🇺🇸Savannah, Georgia, United States
Cancer Center Of Kansas
🇺🇸Wichita, Kansas, United States
Local Institution - 0030
🇺🇸Boston, Massachusetts, United States
Local Institution - 0029
🇺🇸Boston, Massachusetts, 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
The Cancer Center at Presbyterian
🇺🇸Albuquerque, New Mexico, United States
New Mexico Cancer Care Center
🇺🇸Albuquerque, New Mexico, 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
University Of Louisville Medical Center, Inc., Dba
🇺🇸Louisville, Kentucky, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Novant Health Oncology Specialists
🇺🇸Winston-Salem, North Carolina, United States
Charleston Hematology Oncology Associates, Pa
🇺🇸Charleston, South Carolina, United States