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

将 EFIRM 液体活检 (eLB) 升级为 CLIA 认证的实验室开发测试 (eLB-LDT)，用于检测 NSCLC 患者中可操作的 EGFR 突变

• 批准号: 9922667
• 负责人: DAVID S. CHIA
• 金额: $ 39万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-06 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922667
• 关键词: Accreditation; Adenocarcinoma; American; American Society of Clinical Oncology; Asia; Biological Assay; Biopsy; Blinded; Cancer Detection; Cancer Patient; Clinic; Clinical; Clinical Laboratory Improvement Amendments; Clinical Research; Consumption; Country; Data; Decision Making; Detection; Development; Diagnosis; Disease Progression; EGFR gene; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Gefitinib; Gene Mutation; Genes; Genotype; Goals; Health; Healthcare Systems; Human; Human Resources; Intervention; Laboratories; Liquid substance; Los Angeles; Lung diseases; Malignant - descriptor; Malignant neoplasm of lung; Measurement; Medical; Medical center; Molecular; Molecular Profiling; Morbidity - disease rate; Mutation; National Comprehensive Cancer Network; Non-Small-Cell Lung Carcinoma; Normal Cell; Oncogenes; Oncogenic; Pathologist; Patients; Performance; Phase; Physicians; Progression-Free Survivals; Public Health; Resources; Sampling Errors; Specimen; Technology; Testing; Therapeutic; Time; Tissues; Tyrosine Kinase Domain; Tyrosine Kinase Inhibitor; actionable mutation; base; cancer care; cancer cell; chemotherapy; clinical development; clinical practice; clinical research site; college; cost; digital; electric field; equipment training; improved; liquid biopsy; molecular diagnostics; molecular pathology; mortality; mutational status; neoplastic cell; next generation sequencing; novel; targeted treatment; tumor; tumor DNA; validation studies

Project Summary/Abstract: 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 eLB- LDT 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).

项目摘要/摘要： 正常细胞的恶性转化是由关键细胞基因的致癌突变驱动 正在积极开发治疗以靶向这些突变以用于改善发病率的干预措施 和/或死亡率。当前询问这些“可行突变”的临床实践是肿瘤活检 其次是基因分型，这是侵入性的，有时会访问限制性，挑战，但要遵守抽样错误 并且可能根本不可能。液体活检是一个快速新兴领域，可在肿瘤中访问可起作的突变 基于循环肿瘤DNA（CTDNA），在体液中的最小/非侵入性。 该UH2/UH3应用程序对PAR-15-095的响应有助于推进翻译和临床开发 在成熟的学术实验室测定中，EFIRM-Liquid活检（ELB） 在UCLA分子诊断中，修订”（CLIA）认证实验室开发的测试（ELB-LDT） 实验室（MDL），美国病理学家（CAP）认可的实验室。 ELB- LDT将在用于询问NSCLC的EGFR基因的临床环境中评估。 VA大洛杉矶医疗保健系统（VA GLA）的患者。 重要的是要推进癌症检测，诊断和治疗的学术评估以调节临床 将为医生影响患者健康的新功能的测定方法。我们的建议是 推进成熟的学术评估，EFIRM-Liquid活检（ELB），可提供最佳性能技术 为了检测致癌突变，成为经过CLIA认证的实验室开发的测试（LDT），Efirm-liquid 活检实验室开发了测试（ELB-LDT）。 ELB检测NSCLC患者的可起作用EGFR突变 与基于活检的基因分型合作100％一致，优于液体活检的当前技术。这 临床验证研究将在UCLA医疗中心和VA大洛杉矶医疗保健 系统（VA GLA）中有20％的非小细胞肺癌腺癌亚型患者 （NSCLC）EGFR基因中的TKI响应突变。 ELB-LDT技术如果已验证，可以替换 当前的液体活检实践用于EGFR基因分型，因为它具有最佳性能，最低或无创的， 快速，廉价和独立的允许检测最常见的EGFR基因突变 可以用TKI（例如Gefitinib或Erlotinib）治疗，以有效地延长肺的前进生存率 癌症患者。 实现这些目标的两个具体目标。 AIM 1/UH2是适应学术效率 - 液体 活检（ELB）技术成为UCLA诊断学分子病理中的CLIA认证测定法 实验室并确定分析和临床性能。 AIM 2/UH3是在分析和临床上 在临床部位（UCLA和VA GLA）验证ELB-LDT。