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Completed

NCT Number: NCT03001882

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)

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).

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution - 0017, La Louvière, Hainaut, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nivolumab

Biological

Specified dose on specified days

Other names: Opdivo, BMS-936558

Ipilimumab

Biological

Specified dose on specified days

Other names: Yervoy, BMS-734016

Primary outcomes

  1. Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (TMB Cut-point = 16 Mutations/MB)

    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)

    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.

  2. Objective Response Rate (ORR) Per Investigator by Blood TMB (bTMB) Within PD-L1 Subgroup (Blood TMB Cut-point = 21-mutations/MB)

    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)

    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.

  3. Objective Response Rate (ORR) Per Investigator by Tissue TMB Within PD-L1 Subgroup (Tissue TMB Cut-point = 10-mutations/MB)

    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)

    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.

Secondary outcomes

  1. Objective Response Rate (ORR) for All Treated Participants by Investigator Per RECIST 1.1

    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)

    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.

  2. Disease Control Rate (DCR) for Part 1

    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)

    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.

  3. Duration of Response (DOR) for Part 1

    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)

    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.

  4. Time to Response (TTR) for Part 1

    Time frame: From first dose to the time the criteria for Complete Response/Partial Response are first met (Up to approximately 67 months)

    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.

  5. Progression Free Survival (PFS)

    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)

    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.

  6. Overall Survival (OS)

    Time frame: From first dose to the date of death (Assessed up to approximately 67 months)

    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.

  7. Number of Participants With Adverse Events (AEs) for Study Part 2

    Time frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)

    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.

  8. Number of Participants With Serious Adverse Events (SAEs) for Study Part 2

    Time frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)

    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.

  9. Number of Participants With Select Adverse Events (AEs) for Study Part 2

    Time frame: From first dose to 30 days after last dosing date (up to approximately 27 months)

    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.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Collaborators

  • Yale University

Registry information

Official study 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)

Acronym: CheckMate 592

Important dates

Study start
2017
Primary completion
2022
Study completion
2023
First posted
Dec 23, 2016
Registry last updated
May 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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