Early Rebiopsy To Identify Mechanisms And Biomarkers Of Tumor Cell Survival Following Epidermal Growth Factor Receptor (Egfr) Tyrosine Kinase Inhibitor (Tki) Therapy.

TPS9100 Background: Significant advances in the clinical outcomes of lung cancer patients have been achieved in part due to the identification of targetable driver mutations. The success of targeting oncogenic drivers with TKIs has allowed for improvements in response rates, progression free survival and overall survival. Despite these improvements, patients ultimately relapse. Acquired resistance has been evaluated in post-progression tumor samples and is caused by a variety of mechanisms including secondary resistance mutations, gene copy number gains, gene amplification, or bypass pathway activation. Residual tumor burden with surviving cancer cells are the origin of the ultimate tumor progression. Studies analyzing signaling pathways and other markers of these tumor cells or microenvironmental cells in tumor samples before clinical resistance develops are needed to determine how best to target this compartment. Methods: Eligible patients will have a new diagnosis of advanced NSCLC with an EGFR TKI sensitizing mutation. Additional inclusion criteria include ECOG 0-2, a tumor measurable by RECIST 1.1 and at least 2cm in one dimension, and tumor site that is accessible and safe to biopsy. Patients will undergo a pretreatment target lesion biopsy, begin treatment with an EGFR TKI then receive a second biopsy of the same target lesion after two weeks of therapy. Our primary objective is to identify differences between pretreatment and early treatment tumor samples. To do this we will be using a combination of RNA seq, multiplex protein expression analysis and proximity ligation assays. Secondary objectives include identification of predictive markers that can be used to determine which tumors will undergo epithelial to mesenchymal transition or activate other survival pathways and determination of the success rate and adverse event rate of repeat biopsy. Patients are currently being enrolled at a single academic institution however, additional clinical site openings are pending. Our goal enrollment for this study is 47 patients to achieve 20 paired biopsy samples. We will present updated enrollment and demographic information. Clinical trial information: NCT03042221.