Phase 2 Study of Brain Radiotherapy Combined With PD-1PD-L1 Inhibitors and Chemotherapy for Advanced Non-small Cell Lung Cancer Patients Without Driver Mutations and Stable Brain Metastases

What this Trial Is About

Non-small cell lung cancer NSCLC is the most common lung cancer type and often spreads to the brain, leading to brain metastases BM. Historically, survival for advanced NSCLC patients with BM was less than six months using traditional chemotherapy. Recent advances with immune checkpoint inhibitors ICIs, combined with chemotherapy, have shown promising improvements in brain lesion response, progression-free survival, and overall survival. Despite progress, challenges like treatment resistance and recurrence remain. Combining immunotherapy with brain radiotherapy, especially stereotactic radiotherapy SRT, is emerging as a promising approach for patients with limited brain metastases. This phase 2 clinical trial studies the combination of cranial radiotherapy with PD-1PD-L1 inhibitors and chemotherapy in patients with driver gene mutation-negative NSCLC who have stable brain metastases. Patients will be randomly assigned to receive either PD-1PD-L1 inhibitors plus chemotherapy alone or combined with brain radiotherapy using SRT or whole brain radiation therapy WBRT based on their brain metastasis condition. The study aims to evaluate the safety and effectiveness of adding radiotherapy to chemoimmunotherapy. Participants will undergo regular brain MRI scans and systemic assessments before and during treatment. Researchers will monitor objective response rates, intracranial progression-free survival, overall survival, and treatment-related side effects over two years. The study includes careful monitoring for adverse events and will follow patients to assess both brain and overall cancer control. The trial is sponsored by Fudan University and plans to enroll adults aged 18 and older with advanced NSCLC and brain metastases without driver mutations.

Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis