Inclusion Criteria:
1. Age ≥ 18 years and ≤ 60 years.
2. Diagnosis of brain arteriovenous malformation (AVM) confirmed by DSA.
3. Spetzler-Martin grade IV-V
4. No history of rupture of the AVM vessels.
5. No aneurysmal structures that are amenable to interventional embolization.
6. No major surgery within the past 3 months.
7. Able to swallow and retain oral medication, with no significant gastrointestinal abnormalities that could affect drug absorption, such as malabsorption syndrome, bowel obstruction, or extensive gastrointestinal resection.
8. Karnofsky Performance Score ≥ 50%
9. The patient must have adequate organ and bone marrow function, and must not have received blood transfusions or used any supportive medications (such as cytokines or erythropoietin) to elevate white blood cells, platelets, or hemoglobin levels within 7 days prior to screening:
Absolute neutrophil count ≥ 1.0 × 10\^9/L. Hemoglobin ≥ 90 g/L. Platelet count ≥ 100 × 10\^9/L. Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN), patients with Gilbert's syndrome may have ≤ 3.0 × ULN.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
Albumin ≥ 3 g/dL. Creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min. Urine protein \< 2+; if urine protein ≥ 2+, then 24-hour urine protein quantification must be ≤ 1g.
Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
10. The patient must voluntarily sign a written informed consent and be able to complete follow-up visits.
11. For patients of reproductive potential: the patient must agree to use an effective contraceptive method, such as combined hormonal contraception, progestin-only contraception with ovulation suppression, intrauterine device (IUD), intrauterine system (IUS), bilateral tubal ligation, partner's vasectomy, or complete abstinence during the treatment period and for at least 90 days after the last dose of study treatment. Male patients should agree to avoid sperm donation for at least 90 days after the last dose of treatment.
Exclusion Criteria:
1. Patients with multiple arteriovenous malformation lesions (excluding segmental lesions such as CAMS syndrome) or extracranial arteriovenous malformation lesions;
2. Diagnosed with Hereditary Hemorrhagic Telangiectasia (HHT), Capillary Malformation-Arteriovenous Malformation syndrome (CM-AVM), PTEN Hamartoma Tumor Syndrome (PHTS), or CLOVES syndrome;
3. Patients who have received one of the following treatments after birth: a. Stereotactic radiation therapy, surgical treatment, or interventional embolization for BAVM; b. Pharmacological treatment for BAVM; c. Participation in other interventional clinical trials for BAVM;
4. History of ruptured bleeding from malformed vascular clusters or other causes of brain hemorrhage, including subarachnoid hemorrhage, before the screening period;
5. Patients with malignant tumors currently or within the past three years, except for non-melanoma skin basal cell carcinoma, in situ breast cancer, or in situ cervical cancer;
6. Unable to undergo MRI scans and/or have contraindications to MRI (e.g., interference with MRI target lesion volume analysis due to prosthetics, braces, etc.);
7. Unable to undergo DSA and/or have contraindications to DSA (e.g., contrast agent allergy, coagulopathy, etc.);
8. Poorly controlled epilepsy;
9. Uncontrolled, unstable hypertension: Repeated measurements showing systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg with antihypertensive treatment;
10. Dysphagia, active gastrointestinal diseases, malabsorption syndrome, or other conditions affecting the absorption of study drugs;
11. Piror or current retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), glaucoma, or other significant abnormalities in ophthalmologic examinations;
12. Interstitial lung disease, including clinically significant radiation pneumonitis;
13. Cardiac function or comorbidities that meet one of the following conditions: a. Three 12-lead ECG measurements conducted during the screening period at the study center, with an average QTcF \>470 ms calculated using the QTcF formula for the instruments employed; presence of risk factors for QTcF prolongation, such as uncorrectable hypokalemia, inherited long QT syndrome, or taking drugs known to prolong QTcF (mainly Class Ia, Ic, III antiarrhythmic drugs). New York Heart Association (NYHA) functional classification ≥3 congestive heart failure; c. Clinically significant arrhythmias, including but not limited to complete left bundle branch block; d. Documented, clinically significant coronary artery disease, cardiomyopathy, or severe valvular heart disease; e. Echocardiogram showing left ventricular ejection fraction (LVEF) \<50%; f. Bradycardia with a heart rate \<50 beats per minute;
14. Family history of sudden cardiac death before the age of 50 in a first-degree relative;
15. Active bacterial, fungal, or viral infections, including active hepatitis B (positive hepatitis B surface antigen and hepatitis B virus DNA \>1000 IU/ml, or meeting the study center's criteria for active hepatitis B infection), hepatitis C (positive hepatitis C virus RNA), or HIV infection (HIV positive);
16. Pregnant or breastfeeding women;
17. Known allergy to the study drug, other MEK1/2 inhibitors, or excipients;
18. Any other factors determined by the investigator that may lead to forced discontinuation of the trial, such as severe diseases (including psychiatric disorders) requiring concomitant treatment, significant laboratory abnormalities, family or social factors that may affect the subject's safety or data collection.
