Inclusion Criteria:

1. Histologically or cytologically confirmed NSCLC, locally advanced and metastatic
disease stage IIIB and IV. Evidence of disease progression after one or two cytotoxic
treatment regimens which should have included a platinum agent.

2. Complete recovery from prior chemotherapy side effects to < Grade 2.

3. At least one unidimensional measurable lesion meeting RECIST criteria.

4. ECOG PS 0-2.

5. Age > 18 years.

6. Adequate organ function, including:

- Adequate bone marrow reserve: ANC > 1.5 x 109/L, platelets > 100 x 109/L.

- Hepatic: bilirubin <1.5 x ULN, AP, ALT, AST < 1.5 x ULN AP, ALT, and AST <5 x
ULN is acceptable if the liver has tumor involvement

- Renal: calculated creatinin clearance > 40 ml/min based on the Cockcroft-Gault
formula.

7. Estimated life expectancy >12 weeks.

8. Male and female patients with reproductive potential must use an approved
contraceptive method, if appropriate. Female patients with childbearing potential
must have a negative serum pregnancy test within 7 days prior to study enrollment.

9. Signed informed consent.

10. Patient compliance and geographical proximity that allow adequate follow up.

Exclusion Criteria:

1. Pregnant or lactating women.

2. Patients with medical risks because of non-malignant disease as well as those with
active uncontrolled infection.

3. Documented brain metastases unless the patient has completed local therapy for
central nervous system metastases and has been off corticosteroids for at least two
weeks before enrollment.

4. Previous treatment with an EGFR-TKI, or in non-squamous histology earlier treatment
with pemetrexed and in squamous earlier treatment with docetaxel.

5. Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a
5-day period (5 day period for long-acting agents such as piroxicam).

6. Inability or unwillingness to take folic acid, vitamin B-12 supplementation or
dexamethasone.

7. Concomitant treatment with any other experimental drug under investigation.