Abstract B32: RADIANCE: An open-label, nonrandomized, prospective biomarker study to assess analytic concordance between noninvasive testing and tissue testing for EGFR T790M mutation detection in patients with non-small cell lung cancer
Authors: Husain Hatim , Dietrich Martin , Dubinett Steven , Gerber David E. , Gregg Jeffrey , Shiller Michelle , West Howard , Thai Kim , Milner Alvin , Chehab Nabil , Baik Christina 
Published: February 2019

Abstract
Background: EGFR-TKIs are the recommended first-line therapy of patients (pts) with advanced non-small cell lung cancer (NSCLC) who have an EGFR-sensitizing mutation (EGFRm). However, most pts develop resistance to EGFR-TKIs, with the EGFR T790M resistance mutation observed in &gt;50% of pts on first- and second-generation EGFR-TKIs. Osimertinib is a third-generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFRm and T790M resistance mutations, recommended for pts with T790M-positive advanced NSCLC who have progressed on first-line EGFR-TKI therapy. Tumor tissue is the preferred sample source for T790M testing; however, often tumor biopsy is not feasible following disease progression due to inaccessible sites and/or concerns about safety. Testing using plasma samples offers a less invasive, albeit less sensitive, alternative method for the detection of T790M-positive circulating tumor (ct) DNA. Additional noninvasive options, including urine ctDNA analyses, are also being investigated. The RADIANCE trial is designed to determine if urine and plasma tests can provide similar detection rates to tissue testing for T790M detection when combined. Pts identified as T790M-positive may be offered treatment with osimertinib.
Trial Design: RADIANCE (NCT03137264) is an open-label, prospective biomarker study with a primary objective of assessing the analytic concordance between noninvasive testing (Guardant360 Plasma Assay and Trovera Liquid Biopsy Test using urine) and tissue testing (cobas® EGFR Mutation Test v2) for T790M in pts with NSCLC. Approximately 470 pts will be enrolled. The study consists of two parts, Diagnostic Analytic Validity (Part 1) and Clinical Outcomes (Part 2). In Part 1, eligible pts will provide a tumor biopsy (cobas tissue test), plasma (cobas plasma and Guardant360 tests) and urine sample (Trovera test) for T790M testing. Eligibility criteria include a primary diagnosis of EGFRm-positive NSCLC with evidence of disease progression during or following treatment with a first- or second-generation EGFR-TKI. Pts must not be enrolled on another clinical trial, or have previously received osimertinib or another T790M-directed therapy.
In Part 2, pts with T790M-positive status by cobas tissue and/or cobas plasma test will be treated according to standard of care, and may receive osimertinib. Pts will be followed for clinical outcomes for up to 18 months, and evaluated for objective response, progression-free survival, and duration of response (investigator-assessed using RECIST v1.1) and safety. Pts who are T790M negative or do not receive osimertinib will have completed the study after Part 1.
Citation Format: Hatim Husain, Martin Dietrich, Steven Dubinett, David E. Gerber, Jeffrey Gregg, Michelle Shiller, Howard West, Kim Thai, Alvin Milner, Nabil Chehab, Christina Baik. RADIANCE: An open-label, nonrandomized, prospective biomarker study to assess analytic concordance between noninvasive testing and tissue testing for EGFR T790M mutation detection in patients with non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B32.