Personal Genome Diagnostics Inc. — Department of Health and Human Services SBIR Phase I: 102

Description

DESCRIPTION provided by applicant Development of a Non Invasive Plasma Based Test to Stratify Non Small Cell Lung Cancer Patients for Targeted Therapies Lung cancer is the most common and lethal cancer worldwide accounting for million new cases and million deaths in www lung org In the United States alone there will be approximately new cases and deaths in Non Small Cell Lung Cancer NSCLC accounts for of lung cancer DeSantis et al More than of NSCLC patients are diagnosed with metastatic disease and receive systemic treatment Targeted therapies developed recently have increased median survival by in metastatic NSCLC patients whose tumors harbor genetic alterations in specific clinically actionable cancer driver genes Kris et al Therefore clinical guidelines for metastatic NSCLC recommend molecular testing of these genes in stage IV patients to inform choice of targeted therapy Lindeman Cagle Beasley Chitale Dacic Giaccone Jenkins Kwiatkowski Saldivar Squire Thunnissen andamp Ladanyi however rely on the availability of adequate tumor tissue which excludes approximately of metastatic NSCLC patients from targeted interventions Travis et al The purpose of this phase I proposal is to develop and validate LungSelect a non invasive plasma based molecular test for the identification of genetic alterations both sequence mutations and structural alterations in clinically actionable cancer driver genes from circulating cell free DNA cfDNA of metastatic NSCLC patients We envision that the LungSelect test will enable approximately metastatic NSCLC patients to be stratified for FDA approved targeted therapies and late stage clinical trials annually while overcoming the need for tumor tissue that is mandatory for existing tissue based molecular tests Circulating cell free DNA fragments cfDNA are shed into the bloodstream by cells in the body A fraction of cfDNA in the plasma of cancer patients is shed from tumor cells and carries genetic alterations specific to tumor cells Crowley Di Nicolantonio Loupakis andamp Bardelli Reliable detection of tumor specific alterations in plasma can help stratify patients for targeted therapies and overcome the need for tumor tissue by traditional molecular tests To achieve this Personal Genome Diagnostics PGDx proposes to develop and validate LungSelect a non invasive plasma based molecular test for the identification of genetic alterations in clinically actionable genes in cfDNA of NSCLC patients The current phase I proposal consists of three specific aims development of the LungSelect test using digital next generation sequencing based approaches analytical validation of LungSelect and preliminary evaluation of concordance between the genetic alterations identified in matched tumor and plasma samples using LungSelect Pending success of the phase I proposal we will apply for phase II funding to further validate the assay and establish its clinical validity by demonstrating the concordance between time matched tissue and plasma samples in a large cohort of cancer patients Additionally we plan to commercialize the assay to afford NSCLC patients without tumor tissue who currently receive conventional chemotherapy alone the clinical benefit of existing FDA approved targeted therapies PUBLIC HEALTH RELEVANCE Lung cancer is the leading cause of cancer death claiming lives in the U S in Non Small Cell Lung Cancer NSCLC accounts for of lung cancer death and is caused by the accumulation of genetic alterations in cancer driver genes initiating and promoting the uncontrolled growth and metastasis of cancer cells Multiple targeted therapies have been developed which preferentially inhibit cancer cells and limit damage to normal cells Such targeted therapies have increased median survival by over conventional chemotherapy in NSCLC patients whose tumors harbor these genetic alterations Existing molecular tests in NSCLC rely on the availability of adequate tumor tissue but unfortunately approximately of NSCLC patients lack sufficient tumor tissue samples and receive conventional chemotherapy alone Personal Genome Diagnostics proposes to develop and validate LungSelect a non invasive plasma based molecular test for the identification of genetic alterations in clinically actionable genes in cfDNA of NSCLC patients