• Efficacy- overall response rate (CR & PR) according to the RECIST criteria
  
• Safety- drug exposure, adverse events, laboratory tests, vital signs, ECG, and physical examinations
  

• Secondary Efficacy
  
• - compare number of patients who achieve complete response, partial response, or stable disease (CR, PR, SD) between the two treatment groups
  
• - duration of overall response (CR, PR), survival time, and time to disease progression.
  
• - Karnofsky performance status (KPS)
  

Eligible patients will be randomized in a ratio of 2:1 to receive either chemotherapy (a taxane and a platinum compound) plus CPG 7909 Injection or chemotherapy alone. Protocol therapy will be administered until disease progression or intolerable toxicity. CpG 7909 Injection will be administered subcutaneously, on Weeks 2 and 3 of each three-week cycle (days 8 and 15) and chemotherapy will be administered on Week 1 (Day 1). Patients will undergo complete disease evaluation at the end of every other treatment cycle until disease progression.

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer that is beyond surgical cure or that is metastatic (Stage IIIB or IV according to AJCC, Appendix D)
• Patients must have measurable disease according to the RECIST criteria (Appendix F)
• Age > 18 years
• Karnofsky Performance Status of > 70
• Adequate bone marrow reserve as evidenced by WBC > 3,000/mL, ANC > 1,500/mL, and PLT > 100,000/mL
• Adequate renal function as evidenced by serum creatinine < 2.0 mg/dL
• Adequate hepatic function as evidenced by serum total bilirubin < 2.0 mg/dL, AST < 5 X ULN for the reference lab
• Patients must be recovered from the effects of any prior surgery or radiotherapy
• Patients or their legal representatives must be able to understand and provide informed consent to participate in the trial

Exclusion Criteria:

• Patients with active infection or with a fever >38.50 C within three days prior to the first scheduled day of dosing
• Prior treatment with chemotherapy; patients may have received prior radiotherapy
• Patients with suspected or known CNS metastases
• Prior treatment with etanercept, anakinra, leflunomide, or tacrolimus for any reason
• The need for pharmacologic doses of systemic steroids will be excluded; replacement doses, topical or inhalation glucocorticoids are permitted.
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, etc.
• Chloroquine and related compounds within 12 weeks of study entry (1st dose of protocol therapy)
• History of other prior malignancy within the past 5 years other than basal cell carcinoma of the skin or cervical intra-epithelial neoplasia, or cured, early prostate cancer in a patient with PSA < 10 ng/mL
• Patients with known hypersensitivity to any of the components of CpG 7909 Injection or to any of the components of the taxane or platinum drugs
• Patients who have received an investigational therapy within 30 days of study entry (1st dose of protocol therapy)
• Serious medical or psychiatric condition, which would hinder the patient's ability to fully comply with the protocol
• Grade 2 peripheral neuropathy
• Patients who are pregnant or lactating
• Adults of reproductive potential and their partners must agree to use effective contraceptive measures
• History of allogeneic transplant
• Known HIV
• Treatment with hematopoietic growth factors within 4 weeks of the first CpG 7909 Injection