Lorlatinib in ROS1+ NSCLC With Brain Metastasis

NCT07083687 | Not Yet Recruiting Phase 2

• 1 other identifier: HNCH-2025KY34
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Lung Cancer (NSCLC)

Keywords

non-small cell lung cancer; ROS1; lorlatinib

Outcome Measures

Primary Outcomes (1)

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

  up to 26 weeks

Study Arms (1)

100mg lorlatinib QD Orally

EXPERIMENTAL

Drug: Lorlatinib 100 mg

Interventions

Lorlatinib 100 mg DRUG

After enrollment, patients will receive 100 mg of lorlatinib orally once daily until disease progression, unacceptable toxicity, or withdraw study .

100mg lorlatinib QD Orally

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The subject's expected survival time must be 12 weeks or longer.
• Participants must have normal primary organ function and meet the following criteria during screening:
• （1）No blood transfusions within the past 14 days and Adequate hematopoietic function, defined as follows:
• a） Hemoglobin \> 90g/L（without the use of erythropoietin within the past 14 days） b） Absolute Neutrophil Count (ANC) ≥1.5×109/L（without the use of growth factors within the past 14 days） c） Platelets（PLT）≥100×109/L（without the use of platelet-stimulating agents within the past 14 days） （2）Adequate Liver Function, defined as follows：
• Total serum bilirubin ≤1.5 x upper limit of normal (ULN)
• Alanine Aminotransferase（ALT） and Aspartate Aminotransferase（AST）≤3.0 x ULN (≤5.0 x ULN in case of liver metastases) （3）Adequate Renal Function, defined as follows：
• a） Serum creatinine（Cr）≤1.5× ULN or estimated creatinine clearance（CCr）≥45 ml/min （4）Adequate coagulation function, defined as follows：

You may not qualify if:

• Have received treatment with the investigational drug or known allergy to the ingredients or excipients of the investigational drug.
• Concurrent participation in another clinical study, except for observational (non-interventional) clinical studies or subsequent stages of interventional studies.
• Brain metastasis combined with leptomeningeal metastases.
• Brain metastasis with bleeding, or the presence of central nervous system complications requiring urgent local intervention (such as surgery, radiotherapy, etc.).
• Presence of spinal cord compression unless pain symptoms and neurological function have remained stable or improved 2 weeks prior to enrollment.
• Received open surgery (except surgery for biopsy purposes) within ≤14 days prior to enrollment.
• Received intracranial radiotherapy before enrollment.
• 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.
• 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.
• 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.
• Presence of risk factors for QT interval prolongation or increased risk of arrhythmia, such as grade 2 hypokalemia (grade 2 hypokalemia is defined as: blood potassium \< normal lower limit -3.0mmol/L, and with symptoms, requiring treatment), congenital long QT syndrome, family history of long QT syndrome.
• Past or current clinically active interstitial lung disease; presence of pulmonary interstitial fibrosis or active tuberculosis.
• Disorders of swallowing function, active gastrointestinal disease, or other diseases significantly affecting the absorption, distribution, metabolism, and excretion of the investigational drug. History of major gastric resection.
• Presence of other acquired, congenital immunodeficiency diseases, or previous solid organ or hematopoietic stem cell transplantation.
• Evidence of severe or uncontrolled systemic diseases (such as severe mental, neurological diseases, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension i.e., still being greater than or equal to CTCAE 5.0 grade 3 hypertension after drug treatment).

Sponsors & Collaborators

• Hunan Cancer Hospital: lead

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Central Study Contacts

Lin Wu

CONTACT

13170419973; wulin-calf@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2025
• First Posted: July 24, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 24, 2025

Record last verified: 2025-07