Inclusion Criteria:

1. Age 18 years or older, of either sex and of any race.
2. Histologically or cytologically confirmed NSCL.
3. Stage IIIB (with malignant pleural effusion) or stage IV or recurrent disease.
4. Subjects that have recurred or progressed following standard therapy or failed standard therapy; or subjects that are not candidates for or unwilling to undergo standard therapy.
5. Disease that is currently not amenable to curative surgical intervention, due to either non-resectability of the tumor or medical contraindications.
6. Prior VEGF directed therapy
7. Prior chemotherapy
8. At least 4 weeks since prior immunotherapy (eg, IL-2, IFN, etc.) or biological therapy (eg, MABs) prior to the first dose of study drug.
9. At least 1 week since prior treatment with warfarin, acenocoumarol, fenprocoumon, or similar agents.
10. At least 4 weeks since prior systemic hormonal therapy.
11. At least 2 weeks since prior use of herbal preparations/supplements.
12. At least 2 weeks since prior treatment with CYP3A4 inducers or inhibitors.
13. At least 2 weeks since prior radiotherapy to ≤25% of bone marrow, or at least 4 weeks since prior radiotherapy to > 25% of bone marrow.
14. Measurable or evaluable disease; subjects enrolled in the Phase 2a study must have measurable disease by RECIST criteria.
15. ECOG performance 0-1 and life expectancy ≥ 3 months.
16. Ability to give written informed consent.

Exclusion Criteria:

1. Subjects with central lung lesions involving major blood vessels.
2. Primary CNS malignancies or symptomatic CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
3. Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma).
4. Hematologic abnormalities:
5. Serum chemistry abnormalities:
6. Significant cardiovascular disease
7. Subjects with delayed healing of wounds, active gastric ulcers, or unhealed bone fractures.
8. Serious/active infection or infection requiring parenteral antibiotics.
9. Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to administration of first dose of study drug.
10. Inability to comply with protocol requirements.
11. History of ≥ Grade 2 hemoptysis within 6 months prior to administration of first dose of study drug; ongoing bleeding (hemoptysis, hematemesis, hematochezia or melena) or history of clinically significant bleeding within 6 months prior to administration of first dose of study drug.
12. Cerebrovascular accident within 12 months prior to administration of first dose of study drug, or peripheral vascular disease with claudication on walking less than 1 block.
13. Deep venous thrombosis or pulmonary embolus within 6 months prior to administration of first dose of study drug.
14. Subjects with a "currently active" second primary malignancy other than non-melanoma skin cancers or nonmetastatic prostate cancer. Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.
15. If female, pregnant or lactating.
16. No childbearing potential or the use of effective contraception by all fertile male and female subjects during the study and for 30 days after the last dose of study drug. All subjects must agree to use a highly effective method of contraception (including their partner).
17. Known concomitant genetic or acquired immune suppression disease such as HIV.
18. Inadequate recovery from prior antineoplastic therapy.
19. Life-threatening illness or organ system dysfunction compromising safety evaluation.
20. Psychiatric disorder, altered mental status precluding informed consent or necessary testing.