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 solid organ or hematologic transplantation.
10. 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).
11. 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.
12. Severe acute or chronic psychiatric illness, including recent (within the past year) or active suicidal ideation or behavior.
13. 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.
14. In the investigator's judgment, the subject may be unable to complete the study or comply with study requirements.
15. Any other condition that, in the investigator's judgment, would make the subject unsuitable for participation in the study.
