CLRM-10 METIS (EF-25): A PIVOTAL, RANDOMIZED CONTROLLED STUDY OF TUMOR TREATING FIELDS IN PATIENTS WITH 1–10 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER

BACKGROUND: Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division. TTFields treatment showed efficacy in preclinical non-small cell lung cancer (NSCLC) models. Furthermore, TTFields therapy improved survival with a tolerable safety profile in patients with glioblastoma. The objective of the pivotal METIS trial [NCT02831959] is to evaluate the efficacy and safety of TTFields therapy in NSCLC patients with brain metastases. METHODS: NSCLC patients (N=270) with 1–10 brain metastases will be randomized 1:1 to stereotactic radiosurgery (SRS) followed by continuous TTFields therapy using NovoTTF-200M (150 kHz, recommended >18 h/day) with best standard of care (BSC) or SRS followed by BSC alone. Follow-ups will be conducted every 2 months until second intracranial progression. Key inclusion criteria are: Karnofsky Performance Status ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS, and optimal therapy for extracranial disease. Key exclusion criteria are: prior whole brain radiotherapy, single operable, or recurrent brain metastases. Primary endpoint is time to first intracranial progression. Secondary endpoints include time to neurocognitive failure, overall survival, radiological response rate (RANO-BM and RECIST V1.1), quality of life, adverse events, time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases, bi-monthly intracranial progression rate from 2–12 months, and time to second intracranial and distant progression. 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 (DMC) reviewed the study data and recommended continuation as planned. The trial is currently recruiting at 92 sites in North America, Europe, Israel, mainland China and Hong Kong.