CMET-03. PHASE 1 TRIAL OF OSIMERTINIB WITH STEREOTACTIC RADIOSURGERY IN EGFR MUTANT LUNG CANCER BRAIN METASTASIS

Abstract

BACKGROUND: Brain metastases (BM) occurs in 25-40% of patients with non-small cell lung cancer (NSCLC). Traditionally patients with brain metastases were treated with whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgical resection. Historically, BM is associated with dismal prognosis. Recent advances in the targeted therapy have improved BM outcomes. In patients with epidermal growth factor receptor (EGFR) positive NSCLC with 1-10 BM, we hypothesize to control the macro BM with SRS and osimertinib. Osimertinib use will help control the micro metastases. This approach would avoid WBRT that can potentially lead to significant congnitive decline. METHODS: This is single arm, phase I multicenter study of Osimertinib with SRS. Primary endpoint is to determine the safety of Osimertinib in combination with SRS EGFR positive NSCLC with BM. Secondary end points include 6-month intracranial and extracranial progression free survival (PFS-6), overall survival (OS) in EGFR positive NSCLC BM. To compare results of this clinical trial to historical controls of EGFR positive NSCLC BM treated with SRS alone. To assess the intracranial and extracranial overall response rate as measured by RECIST 1.1. Eligibility criteria includes age >18 years, historically confirmed EGFR mutation positive NSCLC with newly diagnosed BM, 1-10 BM, ECOG status of 0-2. Key exclusion criteria include leptomeningeal disease, BM within 5 mm of optic chiasma or optic nerve, metastases in brain stem, history significant cardiovascular and other comorbidities, known HIV or chronic hepatitis infection and those receiving other investigational cancer therapy. Statistical analysis: The study will employ a 3 + 3 design with an expansion cohort at the maximum tolerated dose (MTD) and up-to 40 patients will be enrolled to determine safety and preliminary efficacy with the combination. RESULTS: The study (CASE 3517) is ongoing and enrolling patient with EGFR mutant NSCLC.