Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Multicenter, Randomized, Phase 2 Study of a Recombinant Human Anti-VEGFR-2 Monoclonal Antibody, IMC-1121B in Combination With Platinum-based Chemotherapy Versus Platinum-based Chemotherapy Alone as First-line Treatment of Patients With Recurrent or Advanced Non-small Cell Lung Cancer (NSCLC)
Brief Summary: The purpose of this study is to determine if participants with Stage IV NSCLC have a better outcome when treated with IMC-1121B in combination with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin than when treated with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin alone.


Options:
A: Inclusion Criteria:

* Histologic or cytologic new diagnosis of NSCLC, Stage IIIB with a cytologically positive pleural or pericardial effusion or Stage IV.
* No prior chemotherapy, including adjuvant or neoadjuvant therapy, for the treatment of NSCLC.
* ECOG Performance Status of 2 .
* Patients must be at least 3 weeks since major surgery. Patients must be at least 1 week since surgery, such as 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 greater than or equal to 20 mm with conventional techniques or as greater than 10 mm with spiral CT scan.

Exclusion Criteria:

* Any prior radiation therapy to the thoracic area.
* Active and ongoing systemic infection.
* Prior radiation to greater than 25% of the bone marrow.
* ECOG PS other than 2
* Patients with a known hypersensitivity to gemcitabine and carboplatin.
B: 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)
C: Inclusion Criteria:

1. Patients must be \>=18 years of age.
2. Non-squamous NSCLC (adenocarcinoma or large cell carcinoma). Mixed tumors with small cell anaplastic elements are not eligible. Mixed tumors with squamous histology are acceptable as long as the squamous element is not the dominant histology.
3. Unresectable stage IIIB or stage IV disease. Stage IIIB disease should be ineligible for combined modality therapy (i.e., pleural effusions, pericardial effusions).
4. ECOG performance status of 2.
5. No prior systemic therapy for stage IIIB or stage IV lung cancer.
6. Life expectancy of at least 12 weeks.
7. Patients must have measurable disease per RECIST version 1.1 (see Section 8).
8. Laboratory values as follows:

   * Absolute neutrophil count (ANC) ≥1500/μL
   * Hemoglobin (Hgb) ≥10 g/dL
   * Platelets ≥100,000/μL (≤7 days prior to treatment)
   * AST or ALT and alkaline phosphatase (ALP) must be \<2.5 x ULN, or \<5 x ULN in patients with liver metastases.
   * Total bilirubin \<1.5 x the institutional ULN
   * Calculated creatinine clearance ≥45 mL/min
9. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
10. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
11. Patient must be accessible for treatment and follow-up.
12. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient will be ineligible; sputum cytology alone is unacceptable.
2. Patients with active brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Ideally, patients should not still require use of seizure medication or steroids.
3. Patients who have had major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury within 4 weeks of beginning treatment; or, the anticipation of the need for major surgical procedure during the course of the study.
4. Women who are pregnant or lactating.
5. Minor surgical procedures (with the exception of the placement of portacath or other central venous access) must be completed at least 7 days prior to beginning protocol treatment.
6. History of hypersensitivity to active or inactive excipients of any component of treatment (pemetrexed, bevacizumab, and/or carboplatin).
7. Pulmonary carcinoid tumors.
8. Patients with proteinuria at screening as demonstrated by either:

   * urine protein creatinine (UPC) ratio ≥1.0 at screening OR
   * urine dipstick for proteinuria ≥2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection, and must demonstrate ≤1 g of protein/24 hours to be eligible) (see Appendix B)
9. Patients with a serious non healing wound, active ulcer, or untreated bone fracture.
10. Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
11. Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) within 1 month prior to study enrollment.
12. History of myocardial infarction or unstable angina within 6 months of beginning treatment.
13. Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and /or diastolic blood pressure \>100 mmHg while on antihypertensive medications).
14. New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF) (see Appendix C).
15. Serious cardiac arrhythmia requiring medication.
16. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of treatment.
17. History of stroke or transient ischemic attack ≤ 6 months prior to beginning treatment.
18. Any prior history of hypertensive crisis or hypertensive encephalopathy.
19. History of abdominal fistula or gastrointestinal perforation ≤ 6 months prior to Day 1 of beginning treatment.
20. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
21. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
22. Use of any non-approved or investigational agent ≤ 30 days of administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
23. Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a DFS ≥5 years.
D: 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

Answer: D