Phase II Study of Brigatinib for ALK-positive advanced non-small cell lung cancer with untreated brain metastases (LOGIK2201: BRAVES)

Background The standard of care for patients with advanced Anaplastic lymphoma kinase (ALK)-positive NSCLC is ALK-tyrosine kinase inhibitors (TKIs). At initial diagnosis, 30-35% of patients have brain metastases, which are associated with a poor prognosis. The treatment for brain metastases is based on symptoms due to the brain metastases lesions and the general condition of the patient. ALTA-1L study showed that brigatinib is promising for ALK-positive NSCLC with brain metastases, however, the patients with symptomatic brain metastases were excluded. Thus, it remains unclear whether to treat brain metastases of ALK-positive NSCLC patients with ALK-TKI or local therapy such as surgery or radiotherapy. Methods We have designed a single-arm phase II trial of brigatinib for patients with ALK-TKI naïve ALK-positive NSCLC and at least one brain metastasis ≥5 mm in size that has not been previously treated. Patients will receive brigatinib until disease progression or unacceptable toxicities. Nineteen patients were enrolled by fifteen sites, and enrollment was terminated by September 2025. The primary endpoint is intracranial response rate. Results Intracranial response rate as a primary endpoint and intracranial progression free survival, extracranial response rate, extracranial progression free survival, systemic response rate, systemic progression free survival, overall survival and safety data will be shown. Conclusion If the study demonstrates intracranial efficacy for brigatinib in this patient population, then brigatinib could be a first-choice for ALK-positive NSCLC patients with brain metastases, and radiation therapy or surgery for the brain metastases might be avoided or postponed.