Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy
Brief Summary: This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group \[ECOG\] performance status of 2-3).


Options:
A: 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)
B: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following stage criteria:

  * Stage IIIB disease\* that is not suitable for radical radiotherapy
  * Stage IV disease\* NOTE: \*Radiographically verified
* At least 1 measurable lesion by clinical examination or radiography
* No mixed histologies of small cell lung cancer and NSCLC
* No clinically apparent brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* WBC ≥ 3,000/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL

Hepatic

* AST \< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Alkaline phosphatase \< 3 times ULN
* Bilirubin \< 1.5 times ULN

Renal

* Creatinine clearance ≥ 60 mL/min (by Wright equation) OR ≥ 70 mL/min (by \^51Cr-EDTA clearance)

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able and willing to participate in the quality of life assessment
* No pre-existing neuropathy \> grade 2
* No other malignancy that would preclude study treatment or study comparisons
* No evidence of severe or uncontrolled systemic disease, significant clinical disorder, or laboratory finding that would preclude study participation
* No psychiatric disorder that would preclude study participation
* No other condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy, including neoadjuvant or adjuvant chemotherapy
* No other concurrent cytotoxic chemotherapy

Endocrine therapy

* No concurrent hormonal therapy except contraceptives or replacement steroids

Radiotherapy

* No prior radiotherapy

Surgery

* Recovered from prior surgery
* Prior surgical resection for NSCLC allowed

Other

* More than 12 weeks since prior investigational agents and recovered
* No other concurrent specific antitumor therapy
* No other concurrent investigational agents
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:

* 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

Answer: A