Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases

NCT06282874 | Active Not Recruiting Phase 4

• 1 other identifier: CTONG2303
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Brain Metastases; Leptomeningeal Metastasis; Carcinoma, Non-Small-Cell Lung

Keywords

ALK-Positive Non-Small-Cell Lung Cancer; Brain Metastases; Leptomeningeal Metastasis

Outcome Measures

Primary Outcomes (1)

• intracranial objective response rate（iORR）

  BM Cohort: percentage of participants demonstrating an intracranial complete response or partial response according to modified RECIST v1.1 criteria; LM Cohort: percentage of participants demonstrating an intracranial complete response or partial response according to the imaging criteria of RANO-LM.

  From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.

Secondary Outcomes (5)

• 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.

Study Arms (1)

BM/LM cohort

EXPERIMENTAL

Fifty eligible subjects will be divided into a BM cohort (brain parenchymal metastasis only) and an LM cohort (leptomeningeal metastasis ± brain parenchymal metastasis)

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Lorlatinib 100 mg once daily on days 1 to 28 of each 28-day cycle

Also known as: PF-06463922

BM/LM cohort

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, regardless of sex.
• Histologically or cytologically confirmed ALK-positive NSCLC.
• 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.
• 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.
• 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.
• 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.
• Patients with or without symptoms related to brain and/or leptomeningeal metastases are eligible.
• Life expectancy must be at least 12 weeks.
• ECOG performance status of 0-2 for patients without leptomeningeal metastasis, and 0-3 for patients with leptomeningeal metastasis.
• The investigator considers the subject to have generally adequate major organ function, including hematologic, coagulation, hepatic, renal, and pancreatic function.
• 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.
• 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.

You may not qualify if:

• \. Prior treatment with the investigational drug, or known hypersensitivity to the active substance or any excipients of the investigational drug.
• \. 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.
• In the investigator's judgment, the subject requires urgent local intervention, such as surgery or radiotherapy.
• Presence of spinal cord compression, unless pain symptoms and neurological function have remained stable or improved for at least 2 weeks prior to enrollment.
• Open surgery within 14 days prior to enrollment, except for procedures performed for biopsy purposes.
• 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.
• 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.
• 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.
• Current clinically active interstitial lung disease, or radiation pneumonitis requiring corticosteroid treatment on the day of enrollment.
• 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.
• Other acquired or congenital immunodeficiency disorders, or prior solid organ or hematologic transplantation.
• Evidence of severe or uncontrolled systemic disease, including but not limited to severe psychiatric or neurologic disorders, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic, or renal disease, or uncontrolled hypertension (defined as hypertension that remains at CTCAE version 5.0 Grade 3 or higher despite medical treatment).
• Use or consumption within 2 weeks prior to enrollment of known strong CYP3A4 inhibitors; use within 2 weeks prior to enrollment of known strong CYP3A4 inducers; or use within 2 weeks prior to enrollment of CYP3A4 substrate drugs with a narrow therapeutic index.
• Severe acute or chronic psychiatric illness, including recent (within the past year) or active suicidal ideation or behavior.
• Pregnant or breastfeeding women, or male or female subjects of reproductive potential who refuse to use effective contraception during treatment and for 90 days after the last dose of study drug.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (3)

Tenth Affiliated Hospital, Southern Medical University (Dongguan people's hospital)

Dongguan, Guangdong, 510080, China

Location

The First People's Hospital of Foshan

Foshan, Guangdong, 510080, China

Location

Guangdong Provincial Perople's Hospital

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Meningeal Carcinomatosis

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Meningeal Neoplasms

Study Officials

• Jin-Ji Yang, PhD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, MD

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 28, 2024
• Study Start: August 1, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)