The primary objective of this study is to determine safety and activity of a novel anticancer agent in patients with metastatic non-small cell lung cancer who failed 2 or 3 prior systemic treatments.

Inclusion Criteria:

• presence of measurable, metastatic non-small cell lung cancer (histologically or cytologically confirmed at the time of original diagnosis)
• treatment failure (recurrence, disease progression, or intolerable toxicity) of 2 or 3 prior systemic treatments. (Note: no more than 3 prior systemic regimens for non-small cell lung cancer including adjuvant chemotherapy)
• capable of understanding the nature of the trial and willing to give written informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• hemoglobin level of >=9 g/dL, absolute granulocyte count of >=1.5 × 109/L, and platelet count of >=100 × 109/L
• adequate renal function, as documented by a serum creatinine level of <=1.5 times the institutional upper limit of normal (ULN) and a measured or calculated creatinine clearance of >=60 mL/min
• adequate liver function, as demonstrated by a total bilirubin level of <=1.5 times ULN; levels of serum glutamate oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) <=2 times ULN. If the patient has liver involvement then AST and ALT should be <=5 times ULN
• for men with partners of child-bearing potential and all women of childbearing potential, willingness to use adequate contraception or practice abstinence during the course of the study at least 18 years of age
• life expectancy estimated at greater than 12 weeks

Exclusion Criteria:

• history of blood transfusion within the last 14 days
• need of concurrent administration of allopurinol
• history of radiotherapy or chemotherapy within 4 weeks (nitrosourea or mitomycin C within 6 weeks) of the anticipated first day of dosing (patient must be fully recovered from the acute effects of any prior chemotherapy or radiotherapy)
• any psychological or sociological condition, addictive disorder, or family problems that might preclude compliance with the protocol
• any unstable or severe intercurrent medical condition that in the opinion of the investigator might interfere with achievement of study objectives
• receipt of an investigational agent within 28 days before the anticipated first day of dosing (patient must have recovered from all acute effects of previously administered investigational agents)
• pregnant or breast-feeding
• previous treatment with GARFT inhibitors
• history of radiation therapy to more than 40% of the marrow space
• history of a malignancy (other than non-small cell lung cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years
• active brain metastases (requiring treatment or progressing)