An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV 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 show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.

Official Title
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An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Gemcitabine
* Drug: Pemetrexed
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria Exclusion Criteria: Subjects with untreated Central nervous system (CNS) metastases are excluded Subjects with an active, known or suspected autoimmune disease are excluded Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection Other protocol defined inclusion/exclusion criteria 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 |
| --- | --- |
| Experimental: Arm A: Nivolumab<br>Nivolumab intravenously (IV) as specified | Drug: Nivolumab<br> <br> * Other names: Opdivo;|
| Experimental: Arm B: Nivolumab + Ipilimumab<br>Nivolumab + Ipilimumab IV as specified | Drug: Nivolumab<br> <br> * Other names: Opdivo;Drug: Ipilimumab<br> <br> * Other names: Yervoy;|
| Experimental: Arm C: Nivolumab + Platinum doublet chemotherapy<br>Nivolumab + Platinum doublet chemotherapy (IV) dose as specified | Drug: Nivolumab<br> <br> * Other names: Opdivo;Drug: Carboplatin<br> <br> Drug: Cisplatin<br> <br> Drug: Gemcitabine<br> <br> Drug: Pemetrexed<br> <br> Drug: Paclitaxel<br> <br> |
| Experimental: Arm D: Platinum doublet chemotherapy<br>Chemotherapy administered on specified days of IV chemotherapy | Drug: Carboplatin<br> <br> Drug: Cisplatin<br> <br> Drug: Gemcitabine<br> <br> Drug: Pemetrexed<br> <br> Drug: Paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | approximately 48 months | 
| Progression-free Survival (PFS) as determined by blinded independent central review (BICR) |  | approximately 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer | Up to 48 months | 
| Disease related symptom improvement as measured by the Lung Cancer Symptom Score (LCSS) in all subjects | Disease related symptom improvement assessed at each dosing for 6 months, then every 6 weeks while on treatment | Up to 48 months |