Furmonertinib Combined With Intrathecal Chemotherapy and Stereotactic Radiotherapy (SRT) for EGFR-Mutated NSCLC Patients With Brain Parenchymal and Leptomeningeal Metastases

Inclusion Criteria: * 18 to 75 years old, male or female; * Histopathologically confirmed, unresectable, and not amenable to curative radiotherapy treatment-naïve locally advanced or metastatic lung adenocarcinoma; * The patient was confirmed by a local laboratory to have one of the following EGFR mutations :19Del or L858R; * The patient has not received any systemic anti-tumor treatment in the locally advanced (the researcher judged that it was not suitable for surgery or radiotherapy) or metastatic NSCLC; * At least one measurable tumor lesion (according to RECIST1.1); * Confirm the simultaneous presence of brain parenchymal and meningeal metastasis; * Laboratory tests indicated that the subjects had adequate organ functions, including: 1) ANC ≥1.5×109/L; PLT ≥100×109/L; HGB ≥90g/L; 2) TBIL ≤1.5 times the upper limit of the normal value, AST and ALT ≤2.5 times the upper limit of the normal value (for those with liver metastasis, total bilirubin ≤ 3 times the upper limit of the normal value, AST and ALT≤ 5 times the upper limit of the normal value are allowed); 3) CrCL ≥50 ml/min (calculated according to the Cockcroft-Gault formula); * The ECOG score at the time of screening was 0-2, and there was no significant deterioration of the disease within 2 weeks before the screening; * The expected survival period is greater than 12 weeks; * Non-pregnant female patients of childbearing potential with no pregnancy plan. Female subjects of childbearing potential and male subjects must agree to use effective contraception during the study period and for 6 months after discontinuation of the study drug; * Understand and voluntarily participate in this study and sign the informed consent form. Exclusion Criteria: * Histological or cytological examination suggests NSCLC dominated by squamous cells, or indicates the presence of small cell lung cancer, neuroendocrine carcinoma, etc.； * Patients with other driver genes: ALK, ROS1, RET, BRAF, NTRK, MET, KRAS, etc.. But TP53, RB1, BRAC are not included； * Anticipated requirement for other antitumor therapies beyond this clinical trial during the study period; * Having received any of the following treatments: a) Major surgery within 4 weeks prior to the first dose or during the trial period, excluding procedures such as vascular access establishment, mediastinoscopy, or thoracoscopy for biopsy; b) Use of strong CYP3A4 inhibitors within 7 days or strong CYP3A4 inducers within 21 days prior to the first dose; Use of Chinese herbal medicines or preparations with anti-tumor indications or those adjunctive to cancer therapy within 2 weeks prior to the first dose or expected during the trial period; c) Participation in an investigational drug or device clinical trial within 4 weeks or at least 5 half-lives (whichever is longer) prior to the first dose; d) Treatment with other antitumor drugs within 14 days prior to the first dose; * Patients with symptomatic and unstable pleural or peritoneal effusion; those who have achieved clinical stability for at least 14 days after drainage of pleural effusion or ascites may be enrolled; * Toxicities from prior antitumor therapy have not recovered to ≤ CTCAE grade 1(with the exception of alopecia and residual neurotoxicity from previous platinum-based therapy)； * History of other malignancies or currently concurrent other malignancies (except for malignancies that have undergone radical resection with no recurrence within 5 years, such as cervical carcinoma in situ, basal cell carcinoma of the skin, and papillary thyroid carcinoma); * History of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid treatment; or current clinical manifestations suggestive of ILD; * Severe or uncontrolled systemic diseases requiring treatment including hypertension, diabetes, chronic heart failure (NYHA class III-IV), unstable angina, myocardial infarction within the past year, active hemorrhagic conditions, severe gastrointestinal disorders, active infectious diseases, etc.; * Resting QT interval (QTc) \> 470 msec as measured by clinical ECG screening; Clinically significant prolonged QT interval or other arrhythmias or clinical conditions that may increase the risk of QT prolongation; * Known history of psychiatric disorders or drug abuse, with current active symptoms or ongoing drug use; * Known or suspected hypersensitivity to furmonertinib or any excipients of its formulation; * Female subjects who are pregnant or breastfeeding, or female partners of male subjects who plan to become pregnant during the study period; * The subject demonstrated poor compliance; * Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.