Phase 1 Study of Zorifertinib Combined With Osimertinib for Advanced Non-Small Cell Lung Cancer with Brain and Spinal Cord Membrane Spread After Osimertinib Treatment

What this Trial Is About

Researchers are evaluating the safety and effectiveness of combining Zorifertinib with Osimertinib for people who have advanced Non-Small Cell Lung Cancer NSCLC that has spread to the membranes around the brain and spinal cord, known as leptomeningeal metastases. This study focuses on patients who have already been treated with Osimertinib but experienced progression in the meningeal area. The trial is a Phase 1 study designed to find the recommended dose and further assess safety and treatment response. All participants will receive both Zorifertinib and Osimertinib. Zorifertinib is given orally twice daily at increasing doses starting at 100 mg, while Osimertinib is taken once daily at a fixed dose of 80 mg. The study has two parts Part A involves dose escalation to identify the best dose for further use, and Part B expands the number of participants receiving the recommended dose to evaluate safety, effectiveness, and how the body processes the drugs. Treatment continues until the cancer worsens, side effects become unacceptable, or other stopping criteria are met. Participants will be monitored through regular assessments including neurological exams, brain and spinal imaging, and cerebrospinal fluid tests. Researchers will measure dose-limiting toxicities during the first 21 days, track adverse events and serious side effects for up to 12 months, and evaluate tumor responses using standardized criteria. Outcomes such as progression-free survival, response rates in the brain and overall tumors, and changes in neurological function will be closely followed. The study may last until September 2028, with safety and effectiveness data collected throughout treatment.

Zorifertinib With Osimertinib for NSCLC With Meningeal Progression