Advancing EFIRM-Liquid Biopsy (eLB) to a CLIA-Certified Laboratory Developed Test (eLB-LDT) for Detection of Actionable EGFR Mutations in NSCLC Patients

Malignant transformation of normal cells are driven by oncogenic mutations of key cellular genes where therapeutics are actively being developed to target these mutations for interventions that will improve morbidity and/or mortality. The current clinical practice to interrogate these “actionable mutations” is by tumor biopsy followed by genotyping which is invasive and at times access restrictive, challenging, subject to sampling errors and may simply not possible. Liquid biopsy is a rapidly emerging field to access actionable mutations in tumors minimal/non-invasively in bodily fluids based on circulating tumor DNA (ctDNA). This UH2/UH3 application is responsive to the PAR-15-095 to advance the translational and clinical development of a matured academic laboratory assay, the EFIRM-Liquid Biopsy (eLB) to a “Clinical Laboratory Improvement Amendment” (CLIA)-certified laboratory developed test (eLB-LDT), in the UCLA Molecular Diagnostic Laboratories (MDL), a CLIA-certified/ College of American Pathologists (CAP)-accredited Laboratory. The eLBLDT will be evaluated in a clinical context of use to interrogate actionable mutations in the EGFR gene of NSCLC patients at the VA Greater Los Angeles Healthcare System (VA GLA). It is important to advance academic assays for cancer detection, diagnosis and treatment to regulated clinical assays that will provide novel capabilities to physicians to impact health of their patients. Our proposal is to advance a matured academic assay, EFIRM-Liquid Biopsy (eLB) that delivers the best performance technology to detect oncogenic mutations, to become a CLIA-certified laboratory developed test (LDT), the EFIRM-Liquid Biopsy laboratory developed test (eLB-LDT). eLB detects actionable EGFR mutations in NSCLC patients with 100% concordance with biopsy-based genotyping, outperforms current technologies for liquid biopsy. The clinical validation study will be conducted at the UCLA Medical Center and VA Greater Los Angeles Healthcare System (VA GLA) where 20% of patients with adenocarcinoma subtype of non-small cell lung carcinoma (NSCLC) harbor TKI-responsive mutations in the EGFR gene. The eLB-LDT technology if validated, may replace current practice of liquid biopsy for EGFR genotyping as it has the best performance, minimal or non-invasive, rapid, inexpensive and self-contained permitting the detection of the most common EGFR gene mutations that are treatable with TKI such as Gefitinib or Erlotinib to effectively extend the progression free survival of lung cancer patients. Two Specific Aims are in place to achieve these goals. Aim 1/UH2 is to adapt the academic EFIRM-Liquid Biopsy (eLB) technology to become a CLIA-certified assay in the UCLA Diagnostics Molecular Pathology Laboratory and to determine analytical and clinical performance. Aim 2/UH3 is to analytically and clinically validate eLB-LDT at the clinical sites (UCLA and VA GLA).