Not Yet RecruitingPhase 2

Lorlatinib in ROS1+ NSCLC With Brain Metastasis

21 participantsStarted 2025-08-15

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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Inclusion criteria

✓. Age≥18 years old.
✓. Histologically or cytologically confirmed diagnosis of ROS1+ NSCLC with brain metastases before the use of lorlatinib.
✓. ROS1 rearrangement positive confirmed by IHC FISH, PCR, or next generation sequencing (NGS). Patients with other treatable gene mutations besides ROS1 need to submit for discussion with the study experts to determine eligibility.
✓. Treatment naïve or one prior systemic treatment with platinum-based chemotherapy.
✓. Imaging (MR/CT) confirmed untreated brain metastases before lorlatinib initiation;
✓. Participants with asymptomatic brain metastases or currently unrequiring corticosteroid treatment, or on a stable or decreasing dose of ≤10 mg QD prednisone or equivalent can be enrolled.
✓. According to RECIST 1.1, patients must have at least one at least one measurable intracranial target lesion with the long axis greater or equal to 5 mm at baseline.
✓. Eastern Cooperative Oncology Group Performance (ECOG) score of 0-1.

Exclusion criteria

What they're measuring

Intracranial Objective Response Rate (iORR), based on the modified version 1.1 of the Response Evaluation Criteria in Solid Tumors (RECIST)

Timeframe: up to 26 weeks

Trial details

NCT IDNCT07083687

SponsorHunan Cancer Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-01-01

Contact for this trial

Lin Wu

13170419973 wulin-calf@vip.163.com

View on ClinicalTrials.gov More Lung Cancer (NSCLC) trials