Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer

Exclusion Criteria

• •Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or NSCLC NOS
• •Prior therapy with pemetrexed
• •Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids
• •Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long half-life) or for 2 days (short half-life, if CrCL \<80 mL/min) before pemetrexed dosing and until 2 days after pemetrexed dosing
• •Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the following criteria are met:
• •* brain metastases are stable and have been previously treated with either whole-brain radiotherapy or gamma-knife surgery
• •* steroids are currently not required and more than 14 days since last steroid treatment
• •Symptomatic pleural effusion (\> CTCAE Grade 1 dyspnea) that is not amenable to drainage
• •Treatment with other systemic anticancer therapy within 4 weeks prior to the first dose of study medication
• •Treatment with full field radiation therapy within 4 weeks or limited field radiation therapy within 2 weeks prior to the first dose of study medication
• •Major surgery within 4 weeks or minor surgery within 2 weeks prior the first dose of study medication
• •Elective or a planned major surgery while on study treatment
• •Radiation therapy to greater than 25% of the bone marrow
• •Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)
• •Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct
• •Concurrent active malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• •Pregnant or breast feeding
• •Patients who are taking medications that prolong QT interval and have a risk of Torsades de Pointes (Appendix F) or who have a history of long QT syndrome
• •Patients who are taking medications that are strong inducers or inhibitors of CYP3A4