A Dose Frequency Optimization,Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received Up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks

Study Overview
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Brief Summary
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The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).

Official Title
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A Dose Frequency Optimization, Phase IIIB/IV Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD) Measurable disease before start of pre-study nivolumab treatment Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2 Exclusion Criteria: Carcinomatous meningitis Untreated, symptomatic Central nervous system (CNS) metastases Symptomatic interstitial lung disease Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nivolumab 240 mg<br>Nivolumab 240 mg Every 2 Weeks | Biological: Nivolumab<br> <br> |
| Experimental: Nivolumab 480 mg<br>Nivolumab 480 mg Every 4 Weeks | Biological: Nivolumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Rate (PFSR) at 6 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression. | At 6 Months | 
| Progression Free Survival Rate (PFSR) at 12 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression. | At 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Rate (PFSR) at 24 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression. | At 24 Months | 
| Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months | The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression. | At 12 Months | 
| Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months | The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | At 12 Months | 
| Overall Survival (OS) Rate at 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. | At 12 Months | 
| Overall Survival (OS) Rate up to 60 Months | The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. | From randomization to the date of death, Up to 60 Months | 
| Overall Survival Rate by Histology at 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization. | at 12 Months | 
| Overall Survival Rate by Response Criteria at 12 Months | The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. Complete Response (CR): 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): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization. | 12 Months | 
| Percentage of Participants With an Adverse Events (AEs) | Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants With an Serious Adverse Events (SAEs) | Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death is life-threatening (defined as an event in which the subject 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) requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity is a congenital anomaly/birth defect is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) | Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) | Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants With an Select Adverse Events | Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine. | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants With an Event of Special Interest (ESI) | Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD). | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Percentage of Participants Who Experienced Death | Percentage of Participants who experienced Death due to any cause | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) | 
| Number of Participants With Laboratory Test Abnormalities | Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined) | Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) |