Genomic Landscape of Ceritinib

Further improvements in therapy can only be achieved with a better understanding of the
genomic landscape of ALK rearranged non-small cell lung cancer (NSCLC), specifically at the
time of disease progression following treatment with ALK inhibitors. Recently, secondary ALK
mutations, L1196M and G1269A have been described in patients with acquired resistance to
crizotinib. A small subset of ALK positive lung cancer patients who progressed after
treatment with ceritinib had tumors available for molecular analysis. Secondary mutations
found included G1202R, F1174C, and F1174V. While this is interesting, an unbiased genomic
study (exome or whole genome sequencing) using massively parallel sequencing at the time of
disease progression is critical to fully understand the clonal evolution and the molecular
mechanisms underpinning treatment resistance. To the best of the investigators' knowledge,
such a study has not yet been reported.

The investigators believe the time is ripe now to comprehensively characterize genomic
alterations using massively parallel sequencing technology of ALK driven adenocarcinoma of
the lung to fully understand the clonal heterogeneity before therapy and fully understand the
clonal evolution and the molecular mechanisms underpinning treatment resistance. A better
understanding of genomic alterations through an unbiased comprehensive approach likely would
lead to rationally designed therapy to augment response to ALK inhibitors.

Inclusion Criteria

- Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma.

- Presence of known ALK gene rearrangement.

- Consented to HRPO# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and
Collection of Health Information from Patients with Thoracic Malignancies, Suspected
Thoracic Malignancies, or Mesothelioma") with an existing specimen prior to initiation
of treatment with ceritinib.

- At least 18 years of age.

- Received treatment with standard of care ceritinib