Brief Summary
The purpose of this study is to explore the possible links between participant characteristics and their cancer, with how effective the combination of nivolumab with ipilimumab is, in participants with Stage IV or recurrent Non-Small Cell Lung Cancer (NSCLC).
Brief Title
An Exploratory Study of the Effects of Nivolumab Combined With Ipilimumab in Patients With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically confirmed, stage IV or recurrent non-small cell lung cancer with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease
* Measurable disease by CT or MRI
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Exclusion Criteria:
* Participants with untreated central nervous system metastases
* Participants with active, known or suspected autoimmune disease
* Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)
Other protocol defined inclusion/exclusion criteria apply
* Histologically confirmed, stage IV or recurrent non-small cell lung cancer with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease
* Measurable disease by CT or MRI
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Exclusion Criteria:
* Participants with untreated central nervous system metastases
* Participants with active, known or suspected autoimmune disease
* Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)
Other protocol defined inclusion/exclusion criteria apply
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed, stage IV or recurrent non-small cell lung cancer with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease
* Measurable disease by CT or MRI
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
inclusion/
* Histologically confirmed, stage IV or recurrent non-small cell lung cancer with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease
* Measurable disease by CT or MRI
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03001882
Org Class
Industry
Org Full Name
Bristol-Myers Squibb
Org Study Id
CA209-592
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
An Exploratory Study of the Biologic Effects and Biomarkers of Nivolumab in Combination With Ipilimumab in Subjects With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
Primary Outcomes
Outcome Description
Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.
CR+PR, confidence interval based on the Clopper and Pearson method.
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.
CR+PR, confidence interval based on the Clopper and Pearson method.
Outcome Measure
Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (TMB Cut-point = 16 Mutations/MB)
Outcome Time Frame
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)
Outcome Description
Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.
CR+PR, confidence interval based on the Clopper and Pearson method.
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum.
CR+PR, confidence interval based on the Clopper and Pearson method.
Outcome Measure
Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (Blood TMB Cut-point = 21-mutations/MB)
Outcome Time Frame
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)
Outcome Description
Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Tissue tumor mutational burden (tTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in tumor tissue samples.
CR+PR, confidence interval based on the Clopper and Pearson method.
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
Tissue tumor mutational burden (tTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in tumor tissue samples.
CR+PR, confidence interval based on the Clopper and Pearson method.
Outcome Measure
Objective Response Rate (ORR) Per Investigator by Tissue TMB Within PD-L1 Subgroup (Tissue TMB Cut-point = 10-mutations/MB)
Outcome Time Frame
From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)
Secondary Ids
Secondary Id
2018-000462-11
Secondary Outcomes
Outcome Description
Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
CR+PR, confidence interval based on the Clopper and Pearson method.
Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm.
CR+PR, confidence interval based on the Clopper and Pearson method.
Outcome Time Frame
From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)
Outcome Measure
Objective Response Rate (ORR) for All Treated Participants by Investigator Per RECIST 1.1
Outcome Description
Disease control rate (DCR) is the percent of treated participants with a best overall response of a complete response (CR), partial response (PR), or stable disease (SD), assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1).
PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking smallest sum diameters as reference. PD is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also demonstrate an absolute increase of at least 5 mm. (one or more new lesions is also considered progression). CR+PR, confidence interval based on the Clopper and Pearson method.
PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking smallest sum diameters as reference. PD is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also demonstrate an absolute increase of at least 5 mm. (one or more new lesions is also considered progression). CR+PR, confidence interval based on the Clopper and Pearson method.
Outcome Time Frame
From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)
Outcome Measure
Disease Control Rate (DCR) for Part 1
Outcome Description
DOR is the time between first confirmed response (Complete/Partial Response) and first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who don't progress or die are censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy without prior reported progression were censored at the last evaluable tumor assessment prior to or on the date of subsequent anti-cancer therapy.
PR is at least 30% decrease in the sum of diameters of target lesions, using baseline sum diameters as reference. CR is disappearance of all target lesions and reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). Progressive Disease (PD) is at least 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression). Median computed using Kaplan-Meier method.
PR is at least 30% decrease in the sum of diameters of target lesions, using baseline sum diameters as reference. CR is disappearance of all target lesions and reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). Progressive Disease (PD) is at least 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression). Median computed using Kaplan-Meier method.
Outcome Time Frame
From first dose to the date of the first documented tumor progression or death due to any cause (Up to approximately 67 months)
Outcome Measure
Duration of Response (DOR) for Part 1
Outcome Description
TTR is the time taken from first dosing date to the time the criteria for Complete Response (CR)/Partial Response (PR) are first met.
Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.
Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.
Outcome Time Frame
From first dose to the time the criteria for Complete Response/Partial Response are first met (Up to approximately 67 months)
Outcome Measure
Time to Response (TTR) for Part 1
Outcome Description
PFS is defined as the time from first dosing date to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause.
Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on the date of initiation of subsequent anti-cancer therapy.
Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression).
Median calculated using Kaplan-Meier estimates.
Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on the date of initiation of subsequent anti-cancer therapy.
Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression).
Median calculated using Kaplan-Meier estimates.
Outcome Time Frame
From first dose to the date of the first documented tumor progression or death due to any causes (Assessed up to approximately 67 months)
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
OS is defined as the time from first dosing date to the date of death. If a participant didn't die, OS will be censored on the last date the participant was known to be alive.
Median based on Kaplan-Meier estimates.
Median based on Kaplan-Meier estimates.
Outcome Time Frame
From first dose to the date of death (Assessed up to approximately 67 months)
Outcome Measure
Overall Survival (OS)
Outcome Description
An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment.
An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
Outcome Time Frame
From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Outcome Measure
Number of Participants With Adverse Events (AEs) for Study Part 2
Outcome Description
A Serious Adverse Event (SAE) results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), or requires inpatient hospitalization or causes prolongation of existing hospitalization.
Outcome Time Frame
From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Outcome Measure
Number of Participants With Serious Adverse Events (SAEs) for Study Part 2
Outcome Description
An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment.
An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.
Outcome Time Frame
From first dose to 30 days after last dosing date (up to approximately 27 months)
Outcome Measure
Number of Participants With Select Adverse Events (AEs) for Study Part 2
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone