Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)
Brief Summary: The purpose of the study is to compare the overall survival of BMS-936558 (Nivolumab) as compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy


Options:
A: Inclusion Criteria:

* Newly diagnosed NSCLC in stage IIIB (with a cytologically positive pleural or pericardial effusion) or stage IV, according to the sixth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual37;
* Age \> 18 years;
* No prior chemotherapy, including adjuvant or neoadjuvant therapy, for the treatment of NSCLC;
* Histological confirmation of any non-squamous histological type of NSCLC, given the recent findings of treatment benefit in this population44;
* ECOG performance status of 2;
* At least 3 weeks must have elapsed since major surgery, and at least 1 week since mediastinoscopy, pleuroscopy, or thoracostomy;
* Patients must have measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scan) or as ≥ 10 mm with spiral CT scan;
* Adequate organ function as indicated by the following:

  * White blood cell (WBC) count ≥ 3500/mm3
  * Absolute neutrophil count (ANC) ≥1500/mm3
  * Hemoglobin ≥ 9.0 g/dL
  * Platelet count ≥ 100,000/ mm3
  * Total bilirubin ≤ 2 times the upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times the ULN
  * Estimated glomerular filtration rate (GFR) ≥ 45 mL/min
* Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration;
* Fertile patients (male or female) must agree to use an acceptable method of contraception to avoid pregnancy for the duration of the study and for 3 months thereafter;
* Patients must sign an Informed Consent Form;
* Have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol requirements;

Exclusion Criteria:

* ECOG performance status other than 2;
* Prior chemotherapy for the treatment of NSCLC;
* Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated the patient cannot be included;
* Symptomatic central nervous system (CNS) metastases. Prior CNS metastases are allowed if the patient is neurologically stable and not receiving corticosteroids;
* Serious uncontrolled intercurrent medical or psychiatric illness;
* Active and ongoing systemic infection;
* Second primary malignancy (except in situ carcinoma of the cervix, in situ carcinoma of the bladder, adequately treated basal-cell carcinoma of the skin, adequately treated squamous-cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment and without recurrence);
* Known hypersensitivity to pemetrexed;
* known hypersensitivity to carboplatin;
* Pregnancy or lactation;
* Use of any investigational agent within 30 days prior to enrollment into the study;
* Unable to discontinue administration of non-steroidal anti-inflammatory (NSAIDSs) agents for 2 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with short half-life, such as ibuprofen (total of 5 days), in patients with a GFR between 45 and 79 mL/min; and for 5 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with long half-life (total of 8 days, see 7.4.2) in all patients; patients with a GFR ≥ 80 mL/min may receive concomitant study treatment and ibuprofen or aspirin (≤ 1.3 g/day);
* Inability to comply with requirements and procedures of study.
B: Inclusion Criteria:

* Confirmed NSCLC
* Stage IV disease at the time of study entry
* Measurable disease at the time of study entry
* Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia)
* Adequate hematologic function, hepatic function, renal function and coagulation function
* If sexually active, must be post-menopausal, surgically sterile, or using effective contraception; and agrees to use adequate contraception during the study period and for up to 6 months after the last dose of study medication
* Female participants of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

* Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
* Tumor wholly or partially contains small cell lung cancer
* Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
* Concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
* Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)
* Receiving concurrent treatment with other anticancer therapy
* Has received previous chemotherapy for Stage IV NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
* Has radiologically documented evidence of major blood vessel invasion or encasement by cancer
* Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions)
* Ongoing or active infection
* History of significant neurological or psychiatric disorders
* Experienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmia
* Poorly-controlled hypertension
* Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
* Receiving chronic daily treatment with aspirin (\> 325 mg/day) or other known inhibitors of platelet function
* Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
* Major surgery within 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to randomization
* Elective or a planned major surgery
* Pregnant or lactating
* Any other serious uncontrolled medical disorders or psychological conditions
* Allergy / history of hypersensitivity reaction to any of the treatment components
* History of drug abuse
C: Inclusion Criteria:

* Men \& women ≥18 years of age
* Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for advanced disease
* Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
* Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

* Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent)
* Subjects with carcinomatous meningitis
* Subjects with active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
* Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Prior treatment with Docetaxel
* Treatment with any investigational agent within 14 days of first administration of study treatment

Other protocol-defined inclusion/exclusion criteria apply
D: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
* No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
* No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
* Life expectancy greater than or equal to (\>/=) 8 weeks
* Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants \>= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
* Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
* Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
* Adequate hematologic and end organ function
* Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception

Exclusion Criteria:

Cancer-Specific Exclusion Criteria:

* Participants younger than 70 years who have an ECOG performance status of 0 or 1
* Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled or symptomatic hyerpcalcemia (ionized calcium \> 1.5 mmol/L or calcium \>12 mg/dL or corrected serum calcium \>ULN)
* History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
* National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example \[e.g.\], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
* Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy

General Medical Exclusion Criteria:

* History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
* History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
* Known positivity for human immunodeficiency virus (HIV)
* Known active hepatitis B or hepatitis C
* Active tuberculosis
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
* Prior allogeneic bone marrow transplantation or solid organ transplant
* Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
* Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization

Exclusion Criteria Related to Atezolizumab:

* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
* Oral or IV antibiotic treatment
* Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
* Treatment with systemic corticosteroids or other immunosuppressive medications
* Participants not willing to stop treatment with traditional herbal medicines

Exclusion Criteria Related to Chemotherapy:

* Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is \[i.e.\] vinorelbine, oral or intravenous, and gemcitabine, intravenous)

Answer: C