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

Study Overview
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Brief Summary
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A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival/ resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.

Official Title
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Early Rebiopsy to Identify Mechanisms and Biomarkers of Tumor Cell Survival Following Targeted Therapy in Patients With EGFR, ALK, ROS1 or BRAF Mutations.

Conditions
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Non-Small Cell Carcinoma of Lung, TNM Stage 4, Non-Small Cell Lung Cancer, EGFR Gene Mutation, ALK Gene Mutation, ROSE Cluster 1, BRAF V600E

Participation Criteria
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Eligibility Criteria
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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: erlotinib, gefitinib, rociletinib (CO-1686), afatinib, or 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: intracranial, pleural effusion or any lesion that is deemed unsafe to biopsy by the treating physician or, interventional radiology.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gene expression changes | change from baseline of tumor gene expression profile at 2 weeks. Global gene expression data will be collected using RNAseq | baseline and 2 weeks (+/- 1 week) for each patient. | 
| protein expression change | change from baseline of protein gene expression profile at 2 weeks as measured by multiplex protein assay (proteins to be assayed include: e-cadherin, vimentin, fibronectin, CD4, CD8, CD14, CD16, CD206, PDL1, and CSF1R) | baseline and 2 weeks (+/- 1 week) for each patient. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depth of Response | Correlation between the depths of tumor response (by RECIST v1.1) (percentage decrease in tumor size) with the presence of an EMT signature. | Study startup through 36 months |