A Study of Nivolumab in Advanced Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether nivolumab monotherapy or in combination with Standard of care (SOC) therapies will provide clinical benefit (i.e., PFS, OS, and DOR) without unacceptable toxicity in advanced Non-Small Cell Lung Cancer patients.

Detailed Description
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Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) **Please note that the study is no longer enrolling patients for Groups A, B, C, and E.

Official Title
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A Master Protocol of Phase 1/2 Studies of Nivolumab in Advanced NSCLC Using Nivolumab as Maintenance After Induction Chemotherapy or as First-line Treatment Alone or in Combination With Standard of Care Therapies (CheckMate 370: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 370)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Bevacizumab
* Drug: Pemetrexed
* Other: Best Supportive Care
* Drug: nab-Paclitaxel
* Drug: Paclitaxel
* Drug: Docetaxel
* Drug: Gemcitabine
* Drug: Erlotinib
* Drug: Crizotinib
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Histologically confirmed locally advanced or stage IV NSCLC Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2 Tumor tissue sections must be available for biomarker evaluation Exclusion Criteria: Untreated or active/progressing Central Nervous system (CNS) metastases Active, known or suspected autoimmune disease Known history of testing positive for HIV or AIDS Active or chronic infection of hepatitis B virus or hepatitis C

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 |
| --- | --- |
| Experimental: Group A Nivolumab<br>Opdivo specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;|
| Experimental: Group A Nivolumab + SOC maintenance therapy<br>Opdivo/Bevacizumab specified dose on specified days Opdivo/Pemetrexed specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;Drug: Bevacizumab<br> <br> Drug: Pemetrexed<br> <br> |
| Active Comparator: Group A SOC maintenance therapy<br>Bevacizumab specified dose on specified days Pemetrexed specified dose on specified days | Drug: Bevacizumab<br> <br> Drug: Pemetrexed<br> <br> |
| Experimental: Group B Nivolumab<br>Opdivo specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;|
| Other: Group B Best supportive care<br>Therapy directed against specific symptoms of disease, i.e., palliative radiation or palliative surgery | Other: Best Supportive Care<br>* Palliative radiation, palliative surgery and/or other best supportive care treatments<br>|
| Active Comparator: Group C Investigator's choice chemotherapy<br>Carboplatin/nab-paclitaxel specified dose on specified days Carboplatin/paclitaxel specified dose on specified days Carboplatin/pemetrexed specified dose on specified days Carboplatin/docetaxel specified dose on specified days Carboplatin/gemcitabine specified dose on specified days Paclitaxel specified dose on specified days Docetaxel specified dose on specified days Gemcitabine specified dose on specified days Pemetrexed specified dose on specified days | Drug: Pemetrexed<br> <br> Drug: nab-Paclitaxel<br> <br> Drug: Paclitaxel<br> <br> Drug: Docetaxel<br> <br> Drug: Gemcitabine<br> <br> Drug: Carboplatin<br> <br> |
| Experimental: Group C Nivolumb<br>Opdivo specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;|
| Active Comparator: Group D Erlotinib<br>Erlotinib specified dose on specified days | Drug: Erlotinib<br> <br> |
| Experimental: Group D Nivolumab + Erlotinib<br>Opdivo/Erlotnib specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;Drug: Erlotinib<br> <br> |
| Experimental: Group E Nivolumab + Crizotinib<br>Opdivo/Crizotinib specified dose on specified days | Drug: Nivolumab<br> <br> * Other names: Opdivo;Drug: Crizotinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS), Groups A-D Only | Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. | up to approximately 48 months | 
| Overall Survival (OS), Groups A-C Only | Overall survival (OS) is defined as the time from randomization to the date of death. | up to approximately 60 months | 
| Percentage of Participants With Treatment-related Adverse Events (AEs) Leading to Both Study Drugs Discontinuation, Group E Only | Percentage of participants who experienced a treatment-related AE during the course of the study that lead to discontinuation of both study drugs. | up to approximately 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR), Groups A-D Only | Duration of response (DOR) is defined as the time from first confirmed response (complete response (CR) or partial response (PR)) to the date of the initial objectively documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Median computed using Kaplan-Meier method. | up to approximately 48 months | 
| Objective Response Rate (ORR), Groups A-E | Objective response rate (ORR) is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented tumor progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first. Confidence interval based on the Clopper and Pearson method. | up to approximately 48 months | 
| Overall Survival (OS), Group D Only | Overall survival (OS) is defined as the time from randomization to the date of death. | up to approximately 60 months | 
| Progression-Free Survival (PFS), Group E Only | Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. | up to approximately 48 months |