A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Cetuximab (Erbitux®) in Patients With Non-small Cell Lung Cancer With Progression Following Prior Erlotinib (Tarceva®)

Inclusion Criteria

Inclusion criteria:

1. Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or
recurrent disease following locoregional treatment

2. Either or both of the following:

1) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be
associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from
previous tumor biopsy or surgery 2) Objective clinical benefit from treatment with an
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) as defined by either

1. Documented partial or complete response (Response Evaluation Criteria in Solid
Tumors, RECIST), or

2. Stable disease >=6 months as defined by RECIST in absence of radiographic progression
after initiation of gefitinib or erlotinib.

3. Systemic progression of disease (RECIST v1.1) while on continuous treatment with
erlotinib or gefitinib within the last 30 days. Patients whose disease progresses only in
the central nervous system (CNS) are not eligible 4. No intervening systemic therapy
between cessation of gefitinib or erlotinib and initiation of the treatment in the study
5. Adequate tumor-derived material such as fresh or archived tumor tissue or pleural fluid
from malignant pleural effusion after disease progression on erlotinib/gefitinib prior to
the study entry must be made available for EGFR mutation analyses 6. Patients aged 18
years or older 7. Life expectancy of at least three (3) months 8. Eastern Cooperative
Oncology Group (ECOG) performance score 0-2 9. Written informed consent that is consistent
with ICH-GCP guidelines

Exclusion criteria:

1. Prior treatment with EGFR targeting antibodies; prior severe infusion reaction to a
monoclonal antibody

2. Adverse events due to major surgery (at least 28 days after) or minor surgery not
recovered to CTC grade 1 or less. Surgical wounds must be healing without clinical
evidence of infection prior to study treatment to be eligible.

3. Radiotherapy less than two weeks prior to the start of the study treatment

4. Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved
proteins/antibodies (except erlotinib/gefitinib) <=30 days before study treatment

5. Less than three days from prior treatment with gefitinib or erlotinib. Patients with
adverse events related to gefitinib or erlotinb must recover to CTC AE grade 1 or
less to be eligible.

6. Brain metastases, which are symptomatic. Patients with treated, asymptomatic brain
metastases are eligible if there has been no change in brain disease status for at
least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4)
weeks. Anticonvulsant therapy will be allowed if patient is stable on anticonvulsant
treatment.

7. Other malignancies diagnosed within the past five (5) years (other than non
melanomatous skin cancer, ductal carcinoma in situ and in situ cervical cancer)

8. Known pre-existing interstitial lung disease

9. Significant or recent acute gastrointestinal disorders with diarrhea as a major
symptom e.g., Crohns disease, malabsorption, or Common Toxicity Criteria for Adverse
Events (CTCAE) grade >2 diarrhea of any etiology

10. Women of childbearing potential (WOCBP), or men who are able to father a child,
unwilling to use a medically acceptable method of contraception during the trial;
pregnancy or breast-feeding