Phase IIb/III Randomized, Double-blind Trial of BIBW 2992 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Inclusion Criteria

Inclusion criteria:

1. Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or
Stage IV adenocarcinoma who have failed at least one but not more than two lines of
cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy
regimens must have been platinum-based.

2. Progressive disease following at least 12 weeks of treatment with erlotinib
(Tarceva®) or gefitinib (Iressa®)

3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2

4. Patients with at least one tumor lesion that can accurately be measured by magnetic
resonance imaging (MRI), or computed tomography (CT) in at least one dimension with
longest diameter to be recorded as >20 mm using conventional techniques or >10 mm
with spiral CT scan

5. Male and female patients age >18 years

6. Life expectancy of at least three (3) months

7. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria:

1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1

2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance
non-cancer therapy) or immunotherapy within the past 4 weeks

3. Active brain metastases

4. Significant or recent acute gastrointestinal disorders with diarrhea

5. Patients who have any other life-threatening illness or organ system dysfunction,

6. Other malignancies diagnosed within the past five (5) years

7. Radiotherapy within the past 2 weeks prior to treatment

8. History of clinically significant or uncontrolled cardiac disease

9. Adequate ANC and platelet count

10. Adequate liver and kidney function

11. Patients with any serious active infection including known HIV, active hepatitis B or
active hepatitis C