P3.02a-008 EML4-ALK in Plasma Exosomes from a Cohort of NSCLC Patients: Topic: ALK Biomarkers

Abstract

The identification of EML4-ALK translocations in 3%-5% of NSCLC resulted in the approval of numerous targeted therapies of these lung cancers. Consequently, the availability of new ALK inhibitors forced the development of diagnostic assays, although their validation is limited by the restricted number of available specimens. As the significance of the current standard test (tissue-based FISH) is progressively questioned, development of improved accompanying diagnostics for the predictive biomarker is of high medical need. Overcoming discrepancies of FISH such as tissue sample quality and inter-observer variability, we validated a liquid biopsy test for analysis of EML4-ALK fusion transcripts. For the first time, the availability of a defined cohort of NSCLC patients allowed the determination and clinical interpretation of EML4-ALK in exosomal RNA derived from plasma specimen. We developed and validated an exosome-based biopsy test for EML4-ALK to be run in a CLIA laboratory. The assay enables the discriminative detection of the three major fusion variants v1, v2 and v3 (a,b,c). In detail, exosomal RNA is isolated from low-volume plasma (≤ 2ml) of NSCLC patients and subjected to highly sensitive and specific RT-qPCR. During analysis, each sample is confirmed by defined test controls and process tracking. The final diagnostic results of all clinical specimen are correlated with clinical response data. Section is not applicable. Cohort analysis is ongoing. Therefore, we will submit our results as late-breaking abstract. Section not applicable. We will determine the variant-specific expression of EML4-ALK in plasma samples of a clinically defined, medium-sized NSCLC cohort. Based on specimen data, we are able to test for correlation of the biomarker derived from exosomes with respective tissue results and clinical response of a patient.