Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

The goal of this protocol is to determine mechanisms of resistance to epidermal growth
factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A
number of trials have shown small molecule kinase inhibitors to be active agents in the
treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but
infrequent responses. Mutations in the epidermal growth factor receptor have been shown to
correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most
patients who have initial responses to EGFR-TKI eventually progress. The mechanism of
acquired clinical resistance to these inhibitors in patients incompletely understood.

This is a protocol to study clinical characteristics and biopsy tissue of patients with
non-small cell lung cancer who have had previous clinical response to small molecule kinase
inhibitors and subsequently experience progression of disease. The tissues and other
specimens will be used to carry out laboratory studies to explore the molecular basis of
sensitivity and resistance to small molecule kinase inhibitors.

Inclusion Criteria:

Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and
who fulfill the following eligibility criteria will be considered eligible for this study.

- Patient must have previously received treatment with small molecule kinase inhibitors
targeting at least, in part, EGFR patients may have received other treatments since
treatment with small molecule kinase inhibitors including radiation or chemotherapy)

- Development of disease progression while actively receiving tyrosine kinase inhibitor

- Signed informed consent

Exclusion Criteria: