An Open-label, Single-arm, Multicenter, Prospective Study of Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases

Plain English Summary

Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases is a Phase 4 clinical trial sponsored by Guangdong Association of Clinical Trials studying Carcinoma, Non-Small-Cell Lung, Brain Metastases, Leptomeningeal Metastasis. This study tests the effectiveness of Lorlatinib in patients with a specific type of lung cancer (ALK-positive Non-Small Cell Lung Cancer) that has spread to the brain or leptomeninges. It is for adults (18+) with ALK-positive Non-Small Cell Lung Cancer that has spread to the brain or leptomeninges, who have either not had prior treatment for advanced disease or have progressed on or are intolerant to at least one prior treatment. Participation involves taking Lorlatinib daily. Patients will be closely monitored for side effects and how the cancer responds. Alternative treatments may include other targeted therapies, chemotherapy, radiation therapy to the brain, or supportive care, depending on the patient's specific situation and prior treatments. The trial aims to enroll 41 participants.

Official Summary

This study is an investigator-initiated, prospective, open-label, single-arm, multicenter clinical trial aimed at exploring the antitumor activity of Lorlatinib in ALK-positive NSCLC patients with brain/ leptomeningeal metastases.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with ALK-positive Non-Small Cell Lung Cancer that has spread to the brain or leptomeninges. Patients must have confirmed ALK rearrangement and specific types of brain or leptomeningeal metastases. Individuals who have not received prior systemic treatment for advanced NSCLC, or who have progressed on or are intolerant to at least one prior systemic treatment regimen (including an ALK inhibitor). Patients must have recovered from toxicities of prior treatments to an acceptable level and have adequate organ function. This trial is studying Carcinoma, Non-Small-Cell Lung, Brain Metastases, Leptomeningeal Metastasis, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how well Lorlatinib shrinks tumors in the brain or leptomeninges, indicating its effectiveness in controlling cancer spread to these areas. The specific primary outcome measures are: intracranial objective response rate（iORR） (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This is a Phase 4 (post-marketing) study of a treatment that has already received FDA approval. Phase 4 trials monitor long-term safety, effectiveness in broader patient populations, and potential interactions with other treatments in real-world settings. These studies can involve thousands of patients and help identify rare side effects that may not have appeared in earlier, smaller trials.

Why This Trial Matters

This trial addresses a critical need for effective treatments for ALK-positive Non-Small Cell Lung Cancer that has spread to the brain or leptomeninges, a challenging area with limited options. This research targets Carcinoma, Non-Small-Cell Lung, Brain Metastases, Leptomeningeal Metastasis, where improved treatment options are needed.

Investor Insight

This trial signals potential for Lorlatinib in a specific, difficult-to-treat subset of lung cancer, potentially expanding its market and reinforcing its competitive position in ALK-inhibitor therapy. This treatment is already approved and on the market. This post-marketing study monitors real-world outcomes.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of Lorlatinib, and how it compares to other treatment options for your specific situation. Understand the daily dosing schedule and the importance of attending all scheduled appointments for monitoring and assessments. Be prepared for regular blood tests, imaging scans, and physical examinations to track your response to treatment and any side effects. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 41 participants

Interventions

• DRUG: Lorlatinib — Lorlatinib 100 mg once daily on days 1 to 28 of each 28-day cycle

Primary Outcomes

• intracranial objective response rate（iORR） (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)

Secondary Outcomes

• Progression-free survival (PFS) and intracranial PFS（iPFS） (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
• Obiective response rate (ORR) (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
• Disease control rate (DCR) and intracranial disease control rate (iDCR) (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
• Overall survival (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
• Number of participants with adverse events (From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)

Full Eligibility Criteria

Inclusion Criteria:

1. Age ≥18 years, regardless of sex.
2. Histologically or cytologically confirmed ALK-positive NSCLC.
3. ALK rearrangement positive confirmed by FISH, RT-PCR, IHC Ventana D5F3, or NGS. Patients with other actionable genomic alterations in addition to ALK must be reviewed by the study expert panel to determine eligibility.
4. Patients who have not received prior systemic treatment for advanced NSCLC, or who have experienced disease progression on or intolerance to at least one prior systemic treatment regimen, including an ALK inhibitor, are eligible for enrollment. If the treatment immediately prior to study drug administration was an ALK inhibitor, the washout period may be determined after discussion by the study expert panel.
5. Toxicities related to prior systemic treatment must have recovered to ≤ Grade 1 (CTCAE version 5.0) or to baseline levels, except for adverse events that, in the investigator's judgment, do not pose a safety risk to the subject.
6. At least one CNS lesion meeting one of the following criteria must be present: 1.leptomeningeal metastasis suggested by imaging and/or cerebrospinal fluid findings; cerebrospinal fluid confirmation is not required for imaging-suspected leptomeningeal metastasis; or 2.brain parenchymal metastasis confirmed by magnetic resonance imaging (MRI), with ≥3 brain lesions, or 1-2 lesions that are not suitable for surgery or for which the patient refuses surgery. In patients without leptomeningeal metastasis, at least one measurable brain lesion with a diameter of ≥5 mm is required.
7. Patients with or without symptoms related to brain and/or leptomeningeal metastases are eligible.
8. Life expectancy must be at least 12 weeks.
9. ECOG performance status of 0-2 for patients without leptomeningeal metastasis, and 0-3 for patients with leptomeningeal metastasis.
10. The investigator considers the subject to have generally adequate major organ function, including hematologic, coagulation, hepatic, renal, and pancreatic function.
11. For women of childbearing potential (defined as women who are not postmenopausal for at least 1 year and have not undergone surgical sterilization or hysterectomy), a serum or urine pregnancy test must be performed within 7 days before the first administration of study drug, and the result must be negative. All subjects, male or female, must agree to use adequate contraception throughout the treatment period and for at least 90 days after the last dose of study drug.
12. Subjects must understand and voluntarily sign the written informed consent form, have good compliance, be willing to follow the study treatment plan and visit schedule, and be able to cooperate with safety and efficacy assessments.

Exclusion criteria

1\. Prior treatment with the investigational drug, or known hypersensitivity to the active substance or any excipients of the investigational drug.

2\. Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional study. Subjects who have received any other investigational drug within 28 days before initiation of study treatment are excluded.

1. In the investigator's judgment, the subject requires urgent local intervention, such as surgery or radiotherapy.
2. Presence of spinal cord compression, unless pain symptoms and neurological function have remained stable or improved for at least 2 weeks prior to enrollment.
3. Open surgery within 14 days prior to enrollment, except for procedures performed for biopsy purposes.
4. Fever \>38°C within 1 week prior to enrollment; or clinically significant bacterial, fungal, or viral infection, including but not limited to HIV infection, active HCV infection, or active pulmonary tuberculosis; or infectious complications requiring hospitalization, bacteremia, severe pneumonia, or other clinically significant infections.
5. Clinically significant abnormalities in rhythm, conduction, or morphology on resting electrocardiogram (ECG), such as complete left bundle branch block, second-degree or higher atrioventricular block, clinically significant ventricular arrhythmia, or atrial fibrillation.
6. Current or recent (within 3 months prior to enrollment) unstable angina, congestive heart failure (New York Heart Association Class III or IV), myocardial infarction, coronary artery or peripheral artery bypass grafting, cerebrovascular accident, transient ischemic attack not adequately treated with anticoagulation, or symptomatic pulmonary embolism.
7. Current clinically active interstitial lung disease, or radiation pneumonitis requiring corticosteroid treatment on the day of enrollment.
8. Dysphagia, active gastrointestinal disease, or any other condition that may significantly affect the absorption, distribution, metabolism, or excretion of the investigational drug; or history of major gastric resection.
9. Other acquired or congenital immunodeficiency disorders, or prior s

Trial Locations

• Tenth Affiliated Hospital, Southern Medical University (Dongguan people's hospital), Dongguan, Guangdong, China
• The First People's Hospital of Foshan, Foshan, Guangdong, China
• Guangdong Provincial Perople's Hospital, Guangzhou, Guangdong, China

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• ALK-Positive Lung Cancer
• Brain Metastases
• Leptomeningeal Metastasis
• Lung Cancer
• Cancer
• Metastatic Cancer
• Oncology
• Thoracic Oncology
• Targeted Therapy

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