Prospective observational study for treatment resistance-related gene screening using plasma circulating tumor DNA in the third generation EGFR TKI osimertinib therapy elucidator.

Abstract

TPS3171 Background: Osimertinib (Osi) is a third-generation epidermal growth factor receptor (EGFR) – -tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations (mu). O showed superior efficacy compared with first generation EGFR-TKIs in patients (pts) with previously untreated advanced NSCLC harboring sensitizing EGFR mu in the prior phase III trial. Therefore, Osi is one of the most important standard therapies in EGFR mu positive pts. However, there are few reports about mechanisms of Osi resistance as the first line (1L) EGFR-TKI. Understanding of 1L Osi resistance mechanisms is essential to conduct future therapeutic strategy for EGFR mu NSCLC pts. We planned the analysis of the resistant mechanism by the ultra-sensitive next-generation sequence (NGS) using the circulating tumor (ct) DNA to clarify a resistant mechanism of 1L Osi. Methods: We prospectively collect ctDNA samples from EGFR mu positive NSCLC who will be treated with Osi as 1L. Planned enrollment is 180 cases, we estimate an analysis case at exacerbation to be 120 cases in a registration period and the observation period of for each two years. ctDNA samples are collected at treatment initiation, 3 and 12 months after Osi treatment, and disease progression. We will analyze the mechanisms of 1L Osi by the ultra-sensitive NGS using ctDNA. The key inclusion criteria are histologically or cytologically proven NSCLC, EGFR mu positive, pts treated with Osi as 1L, and written informed consent. The key exclusion criteria are patients who were deemed unsuitable for participation by an attending physician due to other conditions. The primary outcome is to clarify the incidence and ratio of Osi resistance by the ultra-sensitive NGS method using ctDNA at treatment initiation and progression disease. And key secondary endpoint is to examine how the detection quantity of the Osi resistance association mu in ctDNA at treatment initiation influences progressive disease. Clinical trial information: jRCTs031180051.