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)

Non-Small Cell Lung Cancer Clinical Trial

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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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03001882
• Other study ID #: CA209-592
• Secondary ID: 2018-000462-11
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2017
• Est. completion date: April 24, 2023

Study information

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

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: April 24, 2023
• Est. primary completion date: February 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Locations

Country	Name	City	State
Belgium	Local Institution - 0018	Gent
Belgium	Local Institution - 0028	Gent
Belgium	Local Institution - 0017	La Louvière	Hainaut
Belgium	Local Institution - 0027	Liege
Belgium	Local Institution - 0016	Sint-Niklaas
France	Local Institution - 0036	Paris Cedex 5
France	Local Institution - 0033	Pierre Benite
France	Local Institution - 0034	Strasbourg Cedex
France	Local Institution - 0039	Toulon
Germany	Local Institution - 0015	Essen
Germany	Local Institution - 0014	Immenstadt
Germany	Local Institution - 0013	Loewenstein
Germany	Local Institution - 0012	Stuttgart
Italy	Local Institution - 0023	Bergamo
Italy	Local Institution - 0025	Catania
Italy	Local Institution - 0026	Parma
Italy	Local Institution - 0024	Perugia
Netherlands	Local Institution - 0021	Amsterdam
Netherlands	Local Institution - 0022	Nijmegen
Romania	Local Institution - 0011	Cluj-Napoca	Cluj
Romania	Local Institution - 0010	Craiova
Spain	Local Institution - 0031	Barcelona
Spain	Local Institution - 0029	Madrid
Spain	Local Institution - 0030	Madrid
Spain	Local Institution - 0032	Sevilla
United States	Local Institution - 0009	Atlanta	Georgia
United States	Local Institution - 0038	Bronx	New York
United States	Local Institution - 0002	Cleveland	Ohio
United States	Local Institution - 0008	Cleveland	Ohio
United States	Local Institution - 0007	Greenville	South Carolina
United States	Local Institution - 0005	Jacksonville	Florida
United States	Local Institution - 0004	Nashville	Tennessee
United States	Local Institution - 0001	New Haven	Connecticut
United States	Local Institution - 0003	Saint Louis	Missouri
United States	Local Institution - 0006	Springdale	Arkansas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Yale University

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Netherlands,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (TMB Cut-point = 16 Mutations/MB)	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.	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)
Primary	Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (Blood TMB Cut-point = 21-mutations/MB)	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.	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)
Primary	Objective Response Rate (ORR) Per Investigator by Tissue TMB Within PD-L1 Subgroup (Tissue TMB Cut-point = 10-mutations/MB)	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.	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	Objective Response Rate (ORR) for All Treated Participants by Investigator Per RECIST 1.1	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.	From first dose up to approximately 58 months
Secondary	Disease Control Rate (DCR) for Part 1	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.	From first dose up to approximately 58 months
Secondary	Duration of Response (DOR) for Part 1	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.	From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 58 months)
Secondary	Time to Response (TTR) for Part 1	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.	From first dose to the time the criteria for Complete Response/Partial Response are first met (up to approximately 58 months)
Secondary	Progression Free Survival (PFS)	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.	From first dose to the date of the first documented tumor progression or death due to any causes (assessed up to approximately 58 months)
Secondary	Overall Survival (OS)	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.	From first dose to the date of death (assessed up to approximately 58 months)
Secondary	Number of Participants With Adverse Events (AEs) for Study Part 2	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.	From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Secondary	Number of Participants With Serious Adverse Events (SAEs) for Study Part 2	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.	From first dose to 30 days after last dosing date (assessed up to approximately 27 months)
Secondary	Number of Participants With Select Adverse Events (AEs) for Study Part 2	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.	From first dose to 30 days after last dosing date (up to approximately 27 months)

External Links

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