Inclusion Criteria:

1. The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or
fine-needle aspiration.

2. The patient has a diagnosis of either stage IIIB, stage IV, or advanced, incurable
NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen.
(Patients who have failed adjuvant or locally advanced therapy within 6 months are
also eligible to participate in study).

3. The patient has uni-dimensionally measurable NSCLC.

4. Karnofsky performance status >/= 60 or ECOG performance status 0-2

5. The patient has biopsy accessible tumor.

6. The patient has adequate hematologic function as defined by an absolute neutrophil
count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, white blood count (WBC)
>/= 3,000/ mm^3, and hemoglobin >/= 9 g/dL.

7. The patient has adequate hepatic function as defined by a total bilirubin level 1.5 * the upper limit of normal, and alkaline phosphatase, AST or ALT upper limit of normal.

8. The patient has adequate renal function as defined by a serum creatinine level 1.5 mg/dL or a calculated creatinine clearance of >/= 60cc/minute.

9. The patient has Prothrombin time (PT) < 1.5 * upper limit of normal

10. If patient has brain metastasis, they must have been stable (treated or asymptomatic)
for at least 4 weeks after radiation if treated with radiation and not have used
steroids for at least 1 week. Re-imaging performed after 2 weeks, upon completion of
radiation therapy.

11. The patient is >/= 18 years of age.

12. The patient has signed informed consent.

13. The patient is eligible if disease free from a previously treated malignancy, other
than a previous NSCLC, for greater than two years. Patients with a history of prior
basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are exempt
from exclusion.

14. Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation.Childbearing potential will be defined as women who
have had menses within the past 12 months,who have not had tubal ligation or
bilateral oophorectomy.Should a woman become pregnant or suspect that she is pregnant
while participating in this study,she should inform her treating physician
immediately.The patient,if a man,agrees to use effective contraception or abstinence.

15. Subject must be considered legally capable of providing his or her own consent for
participation in this study.

Exclusion Criteria:

1. The patient has received prior investigational therapy, chemotherapy, surgery, or
radiotherapy within 4 weeks of initiating study drug

2. The patient has undergone prior thoracic or abdominal surgery within 28 days of study
entry, excluding prior diagnostic biopsy.

3. The patient has received radiation therapy to the measurable tumor within 6 months.
Patients are allowed to have local irradiation for the management of tumor-related
symptoms (bones, brain). However, if a patient has active new disease growing in the
previously irradiated site, the patient will be eligible to participate in the study.

4. The patient has a significant medical history or unstable medical condition (unstable
systemic disease: congestive heart failure (New York Heart Association Functional
Classification class II or worse), recent myocardial infarction within 3 months,
unstable angina, active infection (i.e. currently treated with antibiotics),
uncontrolled hypertension). Patients with controlled diabetes will be allowed.
Patient must be able to undergo procedure for tissue acquisition.

5. The patient has uncontrolled seizure disorder, active neurologic disease, or
neuropathy >/= grade 2. Patients with meningeal or central nervous System (CNS)
involvement by tumor are eligible for the study if the above exclusion criteria are
not met.

6. The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.

7. Any condition that is unstable or could jeopardize the safety of the patient and its
compliance in the study, in the investigator's judgment.

8. The patient is actively taking herbal remedies or over-the-counter biologics (e.g.,
shark cartilage, high dose antioxidants).

9. Patients will be allowed to have prior biologic (i.e. Vascular endothelial growth
factor (VEGF), epidermal growth factor family (EGFR), etc.) therapy. However, the
patient will be excluded from a given study if he/she has received the same therapy
as the clinical trial (i.e. If a patient has been previously treated with
bevacizumab, they are allowed to enroll in any of the 4 studies. If a patient has
been previously treated with erlotinib, they are excluded from the clinical trials
with erlotinib). In addition, if a patient has been previously treated with gefitinib
(Iressa), they are excluded from the clinical trials with erlotinib.

10. Prior hemoptysis or bleeding diathesis.

11. Hypertension not controlled by medical therapy (systolic blood pressure greater than
160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

12. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B
or C.

13. History of seizure disorder requiring medication (such as steroids or
anti-epileptics).

14. History of organ allograft and bone marrow transplant

15. Previous malignancy (except for cervical carcinoma in situ, adequately treated basal
cell carcinoma, or superficial bladder tumors [Ta, Tis & T1] or other malignancies
curatively treated > 3 years prior to entry).

16. Patients with clinically significant bleeding (e.g., gastrointestinal bleeding)
within the past month prior to study entry are ineligible.

17. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 48 hours of the start of treatment. Both men
and women enrolled in this trial must use adequate barrier birth control measures
(e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral
birth control methods alone will not be considered adequate on this study, because of
the potential pharmacokinetic interaction between BAY 43-9006 and oral
contraceptives.

18. Substance abuse, medical, psychological or social conditions that, in the judgment of
the investigator, is likely to interfere with the patient's participation in the
study or evaluation of the study results.

19. Known allergy to the investigational agent or any agent given in association with
this trial.

20. Concurrent use of St. John's Wort, Rifampicin, and/or ritonavir.