Lorlatinib in ROS1+ NSCLC With Brain Metastasis

Summary

The goal of this Phase II, multicenter, open-label, single-arm clinical trial is to evaluate the intracranial efficacy and safety of lorlatinib in adults with TKI-naïve, advanced ROS1-positive non-small cell lung cancer (NSCLC) and untreated brain metastases. The main questions it aims to answer are: What is the intracranial efficacy (eg., objective response rate/PFS) assessed by revised RECIST v1.1? How do exploratory biomarkers (e.g., ctDNA dynamics in plasma/CSF) correlate with lorlatinib resistance? Participants will: Receive lorlatinib 100 mg orally once daily until disease progression or unacceptable toxicity. Undergo brain MRI/CT scans every 8 weeks (first 12 cycles) and every 16 weeks thereafter. Provide blood samples for safety/biomarker analysis and optional CSF samples via lumbar puncture during scheduled visits.

Timeline

Start

2025-08-15

Primary completion

2027-01-01

Completion

2028-12-01

Drugs

Indications