Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

Inclusion Criteria:

- Carry a diagnosis of stage IV lung adenocarcinoma with an activating mutation
determined to respond to an estimated glomerular filtration rate (EGFR) TKI, alkaline
phosphatase (ALK) or ROS Proto-Oncogene 1 (ROS1) fusion or BRAF V600E.

- Aged 18 - 85 years or older

- ECOG 0-2

- Have a histologically confirmed diagnosis of lung adenocarcinoma harboring an EGFR
sensitizing mutation (including, but not limited to: G719X, del exon 19, or L858R).

- No prior therapy for metastatic disease.

- Planned treatment with a single agent EGFR TKI including but not limited to:

1. erlotinib,

2. gefitinib,

3. rociletinib (CO-1686),

4. afatinib, or

5. osimertinib (AZD-9291).

- Patients must have at least one site of measurable disease ≥ least 2cm.

- Primary disease site or site of metastatic disease must be amenable to biopsy.

- Patients must have the ability to understand and willingness to sign an informed
consent document.

- Patients must be willing to undergo an initial pre-treatment biopsy of tumor tissue
(or have previously collected frozen tissue) and a follow-up biopsy 2 weeks (+/- 1
week) after treatment start

Exclusion Criteria:

- Concurrent health problem which would preclude tissue biopsy (eg hemophilia or other
bleeding predisposition).

- Patients whose only source of biopsiable disease is:

1. intracranial,

2. pleural effusion or any lesion that is deemed unsafe to biopsy by the treating
physician or,

3. interventional radiology.