Inclusion Criteria:

• Age = 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Life expectancy of at least 12 weeks at the pre-treatment evaluation
• Patients with metastatic, measurable, histologically or cytologically documented NSCLC (includes squamous, large cell or adenocarcinoma). In case of unique metastatic site, histological confirmation is required in order to ensure proper diagnosis prior to study entry
• Patients must have progressive NSCLC
• No more than 2 prior systemic agent or regimen at least 28 days prior to study entry. (Prior therapy with gefitinib is allowed but not mandatory)
• Patients must be considered appropriate for systemic anti-cancer therapy by the Investigator
• Patients with at least one uni-dimensional measurable lesion by CT scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Adequate bone marrow, liver and renal function, as assessed by the following laboratory:
• Hemoglobin = 9.0 g/dl
• Absolute granulocytes = 1.5 x 10E9/L
• Platelet count = 100 x 10E9/L
• Total bilirubin < 1.5 x the upper limit of normal
• ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
• PT or INR and PTT < 1.5 x upper limit of normal (except in patients who are on warfarin or heparin. Patients who receive anti-coagulation treatment with an agent such as warfarin or heparin, prophylactically or therapeutically, will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)
• Serum creatinine = 2.0 x upper limit of normal
• Amylase and lipase < 1.5 x the upper limit of normal

Exclusion Criteria:

• Cardiac arrhythmia requiring anti-arrhythmics (excluding beta-blockers or digoxin), symptomatic CAD or ischemia (MI within the last 6 months) or CHF > NYHA Class II
• Uncontrolled hypertension
• Complete renal shut-down requiring hemo- or peritoneal dialysis
• Mixed histologies
• Active clinically serious infections (> grade 2 NCI-CTCAE v3.0)
• Known history of HIV infection or chronic hepatitis B or C
• Known metastatic brain or meningeal tumors, unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. A head CT or MRI must be conducted to rule out brain metastasis or meningeal tumors. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable, provided that the dose is stable for one month prior to and following screening radiographic studies)
• History of seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft and bone marrow transplant
• 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)
• Patients with clinically significant bleeding (e.g., gastrointestinal bleeding) within the past month prior to study entry are ineligible
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days 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
• Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patients participation in the study or evaluation of the study results
• Known allergy to the investigational agent or any agent given in association with this trial
• Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment
• Anti cancer chemotherapy, immunotherapy, vaccines or investigational therapy during the study or within 4 weeks of study entry.
• Radiotherapy during the study or within 4 weeks of study entry. Patients must have recovered from radiation-induced toxicity. However, palliative is allowed for local pain control.
• Any surgical procedure within 4 weeks prior to the start of study drug. Autologous and/or allogenic including mini-allogenic bone marrow transplant or stem cell rescue. Use of biologic response modifiers, such as G-CSF or GM-CSF, during or within 3 weeks of study entry. G-CSF and other hematopoietic growth factors may only be used in the management of acute toxicity, when medically indicated, or at the discretion of the investigator. Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study. Use of St. John's Wort. Use of rifampicin. Prior use of Raf-Kinase inhibitors, MEK or Farnesyl Transferase Inhibitors. Prior use of Bevacizumab and all other drugs that target VEGF/VEGF-Receptors Use of any investigational drug therapy outside of this during or within 4 weeks of study entry.