A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF-06439535 PLUS PACLITAXEL-CARBOPLATIN AND BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER

1. Male and female patients age * 18 years of age, or * age of consent in the region.;2. Newly diagnosed Stage IIIB or IV non-small cell lung cancer (according to Revised International System for Staging Lung Cancer criteria of 2010) or recurrent non-small cell lung cancer (NSCLC).;3. Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC.;4. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).;5. For patients with recurrent disease, at least 6 months must have elapsed since completing adjuvant or neoadjuvant treatment.;6. Screening scan (computed tomography [CT] or magnetic resonance imaging [MRI]) of the head, chest, abdomen (with adrenal glands), and other disease sites, as clinically indicated, to assess disease burden.;7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.;8. Screening laboratory values within the following limits (where deviation of up to 10% is acceptable for any single value if in the investigator*s opinion the patient does not have an increased safety risk):;Bone Marrow Function;a. Absolute neutrophil count (ANC) *1.5 x 109 cells/L (1500/mm3);
b. Platelet count *100 x 109 cells/L (100,000/mm3);
c. Hemoglobin *9.0 g/dL (90 g/L); Renal Function
d. Serum or plasma creatinine *1.5 x upper limit of normal (ULN);;e. Urine dipstick proteinuria <2+ (ie, either 0, trace, or 1+). If urine dipstick is
>1+ then a 24 hour urine for protein must have demonstrated urinary excretion of
*500 mg of protein per day, or urine protein to creatinine ratio (UPC) ratio <1;;Liver Function;f. Total bilirubin *1.5 x ULN (<3 ULN if Gilbert*s disease);;g. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
*3 x ULN (*5 x ULN if liver metastases are present).;9. Recovery (to Grade 1 or baseline) from all clinically significant adverse effects of prior therapies (excluding alopecia).;10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.;11. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.;12. Be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin based on local standard of care, for the treatment of advanced or metastatic non-squamous NSCLC.;13. Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for at least 6 months after the receipt of the last dose of assigned study treatment.;Female patients who are not of childbearing potential (ie, meet at least 1 of the following criteria):;* Have undergone a documented hysterectomy and/or bilateral oophorectomy;;* Have medically confirmed ovarian failure; or;* Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the post-menopausal state.;All other female patients, (including females with tubal ligations) will be considered to be of childbearing potential.

1. Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature.;2. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that is likely to bleed.;3. Known sensitizing EGFR mutations (for example, deletion 19 or L858R) or EML4-ALK translocation positive mutations.If mutation testing is performed, results must be reviewed and confirmed as negative for mutations prior to randomization.;4. History of other cancer within 5 years prior to screening for this study, with the exception of adequately treated ductal carcinoma in situ of the breast, cervical carcinoma in situ, or basal or squamous cell skin cancer.;5. Prior systemic therapy for NSCLC; prior neoadjuvant /adjuvant therapy is allowed if surgical resection for primary disease was performed.;6. History of local radiation for painful bone metastases in the last 2 weeks. (Patients with bone metastases are eligible, however those with symptomatic or painful bone metastases should not have received palliative local radiation for at least 2 weeks prior to randomization).;7. History of hemoptysis (>2.5 mL per event) in the last 3 months or severe bleeding. Evidence of current thrombotic or bleeding disorders. Therapeutic anticoagulation and/or coagulation abnormalities (eg, INR >1.5 and aPTT greater than ULN unless on prophylactic anticoagulation).;8. Medically uncontrolled hypertension or systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg.;9. Peripheral motor or sensory neuropathy with value of * grade 2.;10. Major surgery, or any investigational agents, within 4 weeks before the administration of the first dose of study treatment. Planned major surgery during the treatment period.;11. Any unhealed wound or bone fracture.;12. Active infection. Patients must be off anti-infective agents.;13. Comorbities that would increase the risk of toxicity.;14. Concurrent administration of other anticancer therapies. Bisphosphonate or
Rank-Ligand inhibitor therapy for pre-existing bone metastases or osteoporosis is allowed.;15. Known central nervous system (CNS) metastases, as evidenced by appropriate scans, clinical symptoms, cerebral edema, and/or progressive growth (if a suspected CNS lesion is not confirmed by pathology).Treated and stable (asymptomatic; off steroids) brain metastases are allowed.;16. Active uncontrolled cardiac disease, such as cardiomyopathy, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of *3, unstable angina, or myocardial infarction within 12 months before first dose of study treatment. Clinically significant cardiovascular disease, peripheral vascular disease, transient ischemic attack, cerebrovascular accident.;17. History of severe hypersensitivity reaction to any of the products to be administered during the study, including mammalian cell derived drug products, taxanes, bevacizumab, murine proteins, or excipients in their formulations.;18. Clinical contraindication to treatment with steroids preventing use as part of paclitaxel premedication.;19. Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant; patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study, and for at least 6 months after the receipt of the last dose of study treatment. ;Note: For female patients of childbearing potential, to exclude the possibility of pregnancy, a serum or urine pregnancy test with sensitivity of at least 25 mIU/mL will be performed on 2 occasions by the local certified laboratory, and 2 negative tests are required before receiving the first dose of investigational product. The second negative test should be done during the first 5 days of the menstrual period, immediately preceding the first dose of any study treatment. In the absence of regular menstrual bleeding, the patient should have used
2 different methods of contraception for at least 1 month before the second pregnancy test. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.;Please see the protocol for exclusion criterias 20-25.