Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

Inclusion Criteria: 1. Men and women, ≥18 years of age. 2. Subjects with NSCLC with known ALK-rearrangement tested with FDA-approved test (IHQ or FISH). 3. Subjects with sufficient tissue to test for ALK-rearranged using IHQ or FISH. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 5. Karnofsky Performance Status of ≥70 6. Subjects with histologically confirmed Stage 3B (IIIB), 4 (IV) or recurrent NSCLC (per the 8th International Association for the Study of Lung Cancer classification, non-squamous histology, with prior systemic chemotherapy (platinum-based) given as primary therapy for advanced disease. Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration of the prior regimen occurred at least 3 weeks prior to enrollment. Prior treatment with ALK inhibitors is permitted as long as the last administration occurred 3 weeks prior to enrollment. 7. Subjects with CNS metastases are only eligible if the CNS metastases are adequately treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 1 week prior to randomization. 1. Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3 weeks for neurological stabilization before randomization. 2. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 8. Measurable disease by CT as per RECIST 1.1 criteria. a. The target lesions may be located on a previously irradiated field exists if documented progression of disease (radiographic) in that site. 9. At least 12 weeks of life expectancy. 10. Signed written informed consent 1. Patients should have a signed and dated form of written informed consent approved by the institutional committee in accordance with regulatory and institutional guidelines. This must be obtained before performing any procedure related to the protocol that are not part of the normal care of the patient. 2. Patients must be willing and able to comply with scheduled visits, treatment program, laboratory testing including filling of questionnaires the results reported by the patient and other study requirements. 11. Reproductive Status 1. Women with reproductive potential (WOCBP) should use contraceptive methods based on tables found in Appendix 2. When a teratogenic drug test is used, and / or a drug for which there is not enough information to assess teratogenicity (have not been conducted preclinical studies) are required to use a highly effective method of contraception (failure rate less than 1 % per year). Individual methods of contraception should be determined in consultation with the researcher. 2. The WOCBP must have a negative pregnancy test in serum or urine (minimum sensitivity 25 IU / L or equivalent units of HCG) 24 hours before starting the investigational product. 3. Women should not be breastfeeding. 4. Sexually active men WOCBP should use any method of contraception with a failure rate of less than 1% per year. The investigator should review contraceptive methods and the time period during which contraception to use. Men who are sexually active with WOCBP, follow the instructions of birth control for a period of 90 days, plus the time required for the investigational drug is subject to five half-lives Exclusion Criteria: 1. Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included). 2. Subjects with untreated CNS metastases are excluded. 3. Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. 4. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as Vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 5. Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial 6. Radiographical evidence of cavitated or necrotic tumors 7. Centrally located tumors with radiographical evidence (CT or MRI) of local invasion of major blood vessels 8. History of clinically significant hemoptysis within the past 3 months 9. History of major thrombotic or clinically relevant major bleeding event in the past 6 months. 10. Known inherited predisposition to bleeding or thrombosis 11. Medical History and Concurrent Diseases 1. Any medical condition or serious uncontrolled or active infection with hepatitis or HIV that could be reactivated. 2. Other concurrent malignancies requiring intervention. 3. All toxicities attributed to a previous treatment for cancer other than alopecia or fatigue, must have resolved to Grade 1 (NCI CTCAE version 4) or baseline, prior to administration of study drug. 4. Prior treatment with tumor vaccines or other anti-tumor immune stimulating agents. 5. Prior treatment with Alectinib. 6. Prior treatment with Bevacizumab 7. Subjects with a history of interstitial lung disease. 8. Subjects must be recovered from the effects of major surgery, traumatic injury or substantially at least 7 days before the first dose of study treatment. 12. Physical Findings and Laboratory Tests 1. Positive for the surface antigen of hepatitis B virus (HBV HBsAg) or hepatitis C ribonucleic acid (HCV RNA) Evidence indicating acute or chronic infection 2. Known history of positive test for Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS). 13. Allergies and Adverse Drug Reactions to 1. History of severe hypersensitivity to other monoclonal antibodies. 2. Previous history of severe hypersensitivity reaction to paclitaxel. 3. History of allergy or intolerance (unacceptable adverse event) to components of the study drug, or herbal teas that contain Polysorbate 80. 14. Sexual and Reproductive Status 1. WOCBP pregnant or who are nursing 2. Women with a positive pregnancy test in recruitment or prior to administration of the study drug. 15. Other Exclusion Criteria 1. Any other serious medical condition or uncontrolled active infection, findings on physical examination, laboratory findings, altered mental status, or psychiatric condition that, in the investigator's opinion, would limit the ability of an individual to meet the requirements of study, significantly increase the risk to the subject, or which affects the interpretability of the study results. 2. Prisoners or subjects who are involuntarily incarcerated. 3. Subjects who are compulsorily admitted for treatment of a mental or physical illness (eg, infectious disease). Eligibility criteria for this study were carefully considered to ensure the safety of study subjects, and to ensure that the results of the study can be used