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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
324
Specified Dose on Specified Days
Specified Dose on Specified Days
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.
Time frame: From first dose to database lock (Up to 18 months)
Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2
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.
Time frame: 9 weeks after first dose
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.
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 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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Sharp Memorial Hospital
San Diego, California, United States
Cancer Center Of Central Connecticut
Plainville, Connecticut, 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
University Of Louisville Medical Center, Inc., Dba
Louisville, Kentucky, United States
Johns Hopkins Cancer Center
Baltimore, Maryland, United States
Local Institution - 0029
Boston, Massachusetts, United States
Local Institution - 0030
Boston, Massachusetts, United States
...and 22 more locations
Time frame: From first dose to 30 days post last dose
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.
Time frame: From first dose to 30 days post last dose
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.
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) - 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.
Time frame: 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
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.
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) - 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.
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)
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.
Time frame: From first dose up to approximately 72 months
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.
Time frame: From first dose up to approximately 59 months
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)
Time frame: 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
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)
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)
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)
Time frame: From first dose up to approximately 72 months
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
Time frame: 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
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
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)
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
Time frame: From first dose up to approximately 72 months