Inclusion Criteria:

• Men or women age ≥18 years
• Histologically or cytologically confirmed NSCLC (Recurrent, locally advanced or metastatic, inoperable NSCLC [Stage IIIB/IV]. Patients with Stage IIIB NSCLC must have a cytologically documented pleural effusion.)
• Failed or relapsed after receiving a platinum-containing chemotherapy regimen as first-line therapy for advanced NSCLC
• Measurable disease on computerized tomography (CT) scan
• ECOG Performance Status of 0 or 1
• Expected survival ≥12 weeks
• Provide written informed consent

Exclusion Criteria:

• More than 2 prior chemotherapy regimens
• Progression of disease on prior pemetrexed treatment
• Brain metastases (exception: patients who had a resection and/or completed a course of cranial irradiation, have no worsening CNS symptoms, and have discontinued all corticosteroids for that indication for at least 1 month)
• Serum creatinine ≥2.0mg/dL or creatinine clearance <45mL/min
• Absolute neutrophil count <1500/μL or platelets <100,000/μL
• Any malignancy within 5 years immediately prior to the first dose of study medication (exception: basal cell or non-metastatic squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix)
• Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol
• Patients who are within 28 days of chemotherapy, radiation therapy, immunotherapy, or investigational medication for NSCLC. Patients must have recovered from all of the side effects of treatment.
• Pregnancy or lactation. Women of childbearing potential and non-vasectomized men must agree to use a barrier method of contraception during treatment.