101TiP The efficacy and safety of furmonertinib in advanced NSCLC patients with EGFR mutations and CNS metastases based on ctDNA detection in peripheral blood and CSF (FAITH)

Central nervous system (CNS) metastases including brain metastases (BMs) and leptomeningeal metastases (LMs) are frequent in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), and are associated with poor survival outcomes. Furmonertinib is a highly brain-penetrant, third-generation EGFR tyrosine kinase inhibitor (TKI), which has been approved for the first-line treatment of advanced NSCLC patients with EGFR 19Del or L858R mutations and T790M mutations whose disease has progressed on or after previous EGFR-TKIs. Our two real-world retrospective analyses have indicated the excellent CNS efficacy of high-dose furmonertinib as first-line therapy in advanced NSCLC patients with EGFR mutations and BMs (X. Li. et al. 2023 WCLC) or LMs progressed on previous EGFR-TKIs (X. Li, et al. 2023 ESMO). This FAITH study is a multi-cohort, multi-center, open-label, phase II study. Patients who are aged 18 years or older and have histologically confirmed metastatic NSCLC with EGFR mutations and CNS metastases will receive furmonertinib. Enrolled 120 patients will be divided into four cohorts. Cohort 1: Untreated advanced NSCLC patients with EGFR mutations and BMs receive furmonertinib 160mg orally QD. Cohort 2: Progressed on previous first or second generation EGFR-TKIs advanced NSCLC patients with EGFR mutations and BMs receive furmonertinib 80 mg orally QD. Cohort 3: Progressed on previous third generation EGFR-TKIs therapy advanced NSCLC patients with EGFR mutations and BMs receive furmonertinib 160mg orally QD. Cohort 4: Advanced NSCLC patients with EGFR mutations and LMs receive furmonertinib 160mg orally QD combined with intrathecal chemotherapy. Measurable non-CNS and CNS lesions are assessed by RECIST 1.1. LMs response is assessed by RANO-LM. The primary endpoint is CNS progression free survival (PFS), the secondary endpoints include CNS objective response rate (ORR), CNS disease control rate (DCR), PFS, ORR, DCR and safety. The exploratory endpoint are the resistance mechanisms of furmonertinib and the guidance of ctDNA detection in peripheral blood and cerebrospinal fluid. ChiCTR2300071395. Beijing TianTan Hospital, Capital Medical University. Beijing Natural Science Foundation (7242007) and Beijing Xisike Clinical Oncology Research Foundation (Y-2021AST/zd-0127).