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Lorlatinib in ROS1+ NSCLC With Brain Metastasis | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE2

Lorlatinib in ROS1+ NSCLC With Brain Metastasis

A Phase 2, Multi-Center, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Lorlatinib in TKI naïve, Advanced ROS1-Positive Non-Small Cell Lung Cancer Patients With Brain Metastases

NCT07083687•Hunan Cancer Hospital

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age≥18 years old.
•2. Histologically or cytologically confirmed diagnosis of ROS1+ NSCLC with brain metastases before the use of lorlatinib.
•3. 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.
•4. Treatment naïve or one prior systemic treatment with platinum-based chemotherapy.
•5. Imaging (MR/CT) confirmed untreated brain metastases before lorlatinib initiation;
•6. 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.
•7. 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.
•8. Eastern Cooperative Oncology Group Performance (ECOG) score of 0-1.
•9. The subject's expected survival time must be 12 weeks or longer.
•10. Participants must have normal primary organ function and meet the following criteria during screening:
+7 more criteria

Exclusion Criteria

•1. Have received treatment with the investigational drug or known allergy to the ingredients or excipients of the investigational drug.
•2. Concurrent participation in another clinical study, except for observational (non-interventional) clinical studies or subsequent stages of interventional studies.
•3. Brain metastasis combined with leptomeningeal metastases.
•4. Brain metastasis with bleeding, or the presence of central nervous system complications requiring urgent local intervention (such as surgery, radiotherapy, etc.).
•5. Presence of spinal cord compression unless pain symptoms and neurological function have remained stable or improved 2 weeks prior to enrollment.
•6. Received open surgery (except surgery for biopsy purposes) within ≤14 days prior to enrollment.
•7. Received intracranial radiotherapy before enrollment.
•8. Fever with a temperature above 38℃ within the past week; or clinically significant bacterial, fungal, or viral infection, including but not limited to HIV infection, active HCV infection, active tuberculosis, active hepatitis B (active hepatitis B is defined as HBsAg positive and HBV-DNA copy number exceeds the upper limit of normal in the laboratory of the study center); or infections requiring hospitalization, septicemia, severe pneumonia, etc.
•9. Significant clinical abnormalities in rhythm, conduction, or morphology on resting ECG, such as QT interval (QTc) ≥ 450 ms in males or ≥ 470 ms in females, complete left bundle branch block, 2nd degree or higher heart block, clinically significant ventricular arrhythmia, or atrial fibrillation.
•10. Unstable angina, congestive heart failure (NYHA class III or IV), myocardial infarction, coronary/peripheral artery bypass, cerebrovascular accident, untreated transient ischemic attack, or symptomatic pulmonary embolism occurring currently or within the past 3 months.
+12 more criteria

Key Dates

Start Date

August 15, 2025

Primary Completion Date

January 1, 2027

Completion Date

December 1, 2028

Last Updated

July 24, 2025

Enrollment

ESTIMATED participants

Conditions

Lung Cancer (NSCLC)

Interventions

Lorlatinib 100 mg

DRUG

Contacts

Lin Wu

CONTACT

13170419973 wulin-calf@vip.163.com

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 24, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Lorlatinib in ROS1+ NSCLC With Brain Metastasis

Inclusion Criteria

Exclusion Criteria

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