RTID-06. THE PIVOTAL METIS (EF-25) STUDY OF TUMOR TREATING FIELDS (TTFIELDS) THERAPY FOR BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC) FOLLOWING RADIOSURGERY

Abstract

Abstract INTRODUCTION: TTFields are electric fields that disrupt processes necessary for cancer cell survival and can stimulate an antitumor immune response in preclinical NSCLC models. TTFields therapy is a noninvasive and locoregional treatment approved for glioblastoma, which has recently demonstrated a survival benefit when applied to the thorax with standard of care (SOC) systemic therapy in patients with metastatic NSCLC that progressed on/after platinum. Here we describe the pivotal METIS study (EF-25, NCT02831959) evaluating the efficacy and safety of TTFields therapy applied to brain metastases from NSCLC. TRIAL DESIGN: Patients (270) with 1–10 brain metastases from NSCLC will receive stereotactic radiosurgery (SRS), followed by 1:1 randomization to TTFields (NovoTTF-200M [150 kHz] applied to the head ≥ 18 h/day) with best SOC, or best SOC alone. Key inclusion criteria are life expectancy ≥ 3 months, a new diagnosis of 1 inoperable or 2–10 supra and/or infratentorial brain metastases from NSCLC, that are amenable to SRS. Patients who had prior whole brain radiotherapy, or have single operable, leptomeningeal, or recurrent brain metastases, certain genetic mutations, or severe comorbidities or contraindications, are not eligible. The primary endpoint is time to first intracranial progression. Secondary endpoints include time to neurocognitive failure, overall survival, radiological response rate, time to second intracranial progression, time to first/second intracranial progression by modified RECIST v1.1, rate of intracranial progression, time to distant progression, rate of cognitive decline, quality of life, neurocognitive failure-free survival, and safety. The study is powered at 80% (2-sided alpha of 0.05) to detect a hazard ratio of 0.57. In July 2021, an independent Data Monitoring Committee reviewed the study data and recommended continuation. The study includes 128 sites in Europe, Israel, mainland China, North America, and Hong Kong. The final patient was enrolled in March 2023.