Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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)
Brief Summary: 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.


Options:
A: Core Inclusion Criteria:

* Histologically confirmed PD-L1 status defined NSCLC. Biopsy must be within 70 days of first treatment with pembrolizumab.
* Eastern Cooperative Oncology Group (ECOG) performance status 2.
* Life expectancy \> 12 weeks.
* Uni-dimensionally measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
* Computerised Tomography (CT) scan of chest and abdomen within 28 days of starting pembrolizumab.
* Adequate haematological function:

  * Platelet count ≥100 x 109 /L.
  * Neutrophils ≥1.5 x 109/L.
  * Haemoglobin ≥ 90 g/L.
* Adequate hepatic function:

  * Serum bilirubin ≤1.5 x upper limit of normal (ULN).
  * Serum transaminases ≤2.5 x ULN.
* Adequate renal function: Creatinine clearance \<1.5 times ULN concurrent with creatinine clearance \>50 ml/min.
* Provision of signed and dated, written informed consent prior to any trial specific procedures, sampling and analyses.

Core Exclusion Criteria:

* Patients who do not meet the criteria of performance status = 2 on the ECOG Performance scale.
* Untreated symptomatic brain or leptomeningeal metastatic disease.
* Medical or psychiatric conditions compromising informed consent.
* Any medical condition which in the opinion of the investigator would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol.
* Radiotherapy within 28 days of trial treatment.
* Active autoimmune disease that has required systemic treatment in past 2 years
* Chronic usage of steroids or other immunosuppressant medication.
* Previous history of pneumonitis.
* Any evidence of clinical autoimmunity.
B: 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
C: Inclusion Criteria:

* Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer \[AJCC\] 7th edition) squamous NSCLC.
* Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
* Has not received prior systemic treatment for metastatic NSCLC.
* Has provided tumor tissue from locations not radiated prior to biopsy.
* Has a life expectancy of at least 3 months.
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
* Has adequate organ function.
* If female of childbearing potential, is willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of study drug.
* If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria:

* Has non-squamous histology NSCLC.
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
* Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (\<3 weeks prior to first dose).
* Received radiation therapy to the lung that is \> 30 Gy within 6 months of the first dose of study drug.
* Completed palliative radiotherapy within 7 days of the first dose of study drug.
* Is expected to require any other form of antineoplastic therapy while on study.
* Has received a live-virus vaccination within 30 days of planned treatment start.
* Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
* Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
* Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
* Has active autoimmune disease that has required systemic treatment in past 2 years.
* Is on chronic systemic steroids.
* Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.
* Has participated in any other pembrolizumab trial and has been treated with pembrolizumab.
* Has an active infection requiring therapy.
* Has known history of Human Immunodeficiency Virus (HIV).
* Has known active Hepatitis B or C. Active Hepatitis B.
* Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).
* Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
D: Inclusion Criteria:

* Signed written informed consent
* Cytologically or histologically proven NSCLC (adenocarcinoma, squamous cell carcinoma, large-cell carcinoma)
* Stage IV or non-treatable by radiotherapy or surgery stage III (7th classification)
* No previous systemic chemotherapy for lung cancer, except in case of relapse after adjuvant treatment for localized disease with 6 months or more between end of previous chemotherapy and relapse
* Patients less than 70 years old and PS 2 or 70 years older PS 0 to 2
* Judged fit enough to receive a carboplatin based doublet according to ESMO guidelines
* Presence of at least one measurable target lesion (RECIST 1.1 rules) in a non-irradiated region and analysable by CT
* Life expectancy superior at 12 weeks
* Prior radiation therapy is authorized if it involved less than 25% of the total bone marrow volume and finished 14 days before D1 of planned treatment
* Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration WBC superior or equal at at 2000/μL Neutrophils superior or equal at at 1500/μL Platelets superior or equal at at 100 x103/μL Hemoglobin superior at 10.0 g/dL Serum creatinine inferior or equal at 1.5 x ULN or creatinine clearance (CrCl) superior or equal at at 45 mL/min (if using the Cockcroft-Gault formula ) AST/ALT inferior or equal at 3 x ULN Total Bilirubin inferior or equal at 1.5 x ULN (except Patients with Gilbert Syndrome, who can have total bilirubin inferior at 3.0 mg/dL)
* Availability of adequate FFPE tumor-derived material (tumor blocks or slides) from a biopsy, surgery or fine needle aspirate for analysis of PD-L1 testing by IHC

Age and Reproductive Status

• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during treatment.

WOCBP should use an adequate method to avoid pregnancy :

* For 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab + ipilimumab,
* For 4 weeks after the last dose of carboplatine + pemetrexed,
* For 5 weeks after the last dose of carboplatine + paclitaxel.

  * Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of treatment
  * Women must not be breastfeeding
  * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during treatment Men will be instructed to adhere to contraception for a period of 31 weeks after the last dose of nivolumab + ipilimumab and with carboplatine +pemetrexed or carboplatine + paclitaxel up to 6 months thereafter.

Exclusion Criteria:

* Patients with other severe concurrent disorders that occurred during the prior six months before enrollment (myocardial infection, severe or unstable angor, coronarian or peripheric arterial bypass operation, NYHA class 3 or 4 congestive heart failure, transient or constituted cerebral ischemic attack, at least grade 2 peripheral neuropathy, psychiatric or neurological disorders preventing the patient from understanding the trial, uncontrolled infections) are not eligible.
* Serious or uncontrolled systemic disease judged as incompatible with the protocol by the investigator
* Another previous or concomitant cancer, except for basocellular cancer of the skin or treated cervical cancer in situ, or appropriately treated localized low-grade prostate cancer (Gleason score inferior at 6), unless the initial tumor was diagnosed and definitively treated more than 5 years previously, with no evidence of relapse.
* Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation
* Superior at caval syndrome
* Uncontrolled infectious status
* All concurrent radiotherapy
* Concurrent administration of one or several other anti-tumor therapies.
* Psychological, familial, social or geographic difficulties preventing follow-up as defined by the protocol.
* Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor),
* Concurrent participation in another clinical trial
* Patients are excluded if they have active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for \[lowest minimum is 4 weeks or more\] after treatment is complete and within 28 days prior to the first dose of nivolumab and ipilimumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (superior at 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
* Patients should be excluded if they have an active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
* Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (superior at 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses superior at 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
* Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Patients should be excluded if they have a lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
* Allergies and Adverse Drug Reaction
* History of allergy to study drug components
* Severe spinal hypoplasia and / or hemorrhagic tumors

Answer: B