Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI

Inclusion Criteria: * 1\. Have fully understood the study and voluntarily signed the Informed Consent Form (ICF). 2\. Subjects must be 18-75 years old before signing the Informed Consent Form (ICF). 3\. During the screening phase, subjects must be diagnosed with non-small cell lung cancer (NSCLC) and test positive for EGFR-sensitive mutations (L858R and/or Exon 19Del). 4\. Subjects who developed leptomeningeal progression after treatment with third-generation EGFR-TKIs and have no extracranial progression. The original third-generation EGFR-TKIs may be continued at the original dose or reduced dose. 5\. Subjects diagnosed with leptomeningeal metastasis must have positive cerebrospinal fluid (CSF) cytology results. Subjects with negative CSF cytology but clinically diagnosed leptomeningeal metastasis based on symptoms, brain or spinal MRI imaging are also eligible for enrollment. 6\. Subjects with both leptomeningeal progression and brain parenchymal progression are allowed to enroll. 7\. Have undergone Ommaya reservoir implantation, with confirmation of no surgery-related complications and normal function of the Ommaya reservoir. 8\. If accompanied by neurological symptoms, the following conditions must be met: able to take oral medication and swallow drugs; no need to increase hormone dosage to control central nervous system symptoms for at least 1 week prior to study treatment (i.e., symptom stability). 9\. All anti-tumor therapy-related toxicities must have recovered to ≤ Grade 1 per CTCAE 5.0 criteria prior to starting study treatment (neurotoxicity related to platinum-based therapy may recover to ≤ Grade 2 per CTCAE 5.0 criteria); alopecia of any grade is allowed for enrollment. 10\. Screening period test results must meet the following criteria: * Neutrophil count ≥ 1.5 × 10⁹/L * Platelet count ≥ 100 × 10⁹/L * Hemoglobin ≥ 90 g/L * Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (calculated via Cockcroft-Gault formula) ≥ 50 mL/min * Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN allowed for patients with Gilbert syndrome or liver metastasis) * Aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis) * Alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis) 11. Estimated survival duration ≥ 3 months. 12. Karnofsky Performance Status (KPS) score ≥ 60. Exclusion Criteria: * 1\. Subjects with a history of cranial or spinal radiotherapy within 6 months prior to study drug administration are ineligible for enrollment. Radiotherapy for bone metastases within 3 months prior to study drug administration is also not permitted. 2\. Subjects who have undergone major surgical procedures (e.g., intrathoracic, intra-abdominal, or pelvic surgery) within 4 weeks prior to the first dose of study treatment, or who have not yet recovered from side effects related to such surgeries, are ineligible for enrollment. 3\. Subjects with any other currently active malignant tumor besides NSCLC are excluded. 4\. Subjects with clinically significant, uncontrolled cardiac disease and/or cardiac events occurring within the past 6 months, such as: 1. Myocardial infarction within 6 months prior to screening; 2. Documented history of heart failure (NYHA Class III-IV); 3. Uncontrolled hypertension: systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, regardless of antihypertensive medication use (adjustment of antihypertensive drugs prior to screening is permitted); 4. Drug-refractory arrhythmias; 5. Screening QTcF \>470 ms; 6. Left ventricular ejection fraction (LVEF) \<50%. 5. Subjects with gastrointestinal diseases or severe impairment of gastrointestinal function that may significantly affect drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 6\. Subjects unable to discontinue the following medications within 1 week prior to study drug administration and during the study period: 1. Strong inducers or strong inhibitors of CYP3A4; 2. Drugs that may prolong the QT interval or induce torsades de pointes. 7. Subjects with prior or current HIV infection are excluded. HCV antibody-positive subjects may be enrolled if HCV RNA is undetectable (with the lower limit of detection defined per each center's standards) and there is no concurrent hepatitis B virus (HBV) infection. HBV-infected subjects may be enrolled if they meet the following conditions: <!-- --> 1. For active hepatitis B patients: at least 6 weeks of antiviral therapy prior to starting study treatment, with HBV DNA \<100 IU/mL and ALT/AST levels \<ULN; 2. For resolved or chronic hepatitis B patients: at least 2 weeks of prophylactic antiviral therapy prior to starting study treatment, with HBV DNA below 100 IU/mL (e.g., inactive carriers) and ALT/AST levels \<ULN. 8\. Pregnant or breastfeeding women; women of childbearing potential must agree to use highly effective contraception during the treatment period and for 3 months after the last dose; fertile men must also use highly effective contraception during the treatment period and for 6 months after the last dose. 9\. Subjects with a prior history of interstitial lung disease, including clinically significant radiation pneumonitis (e.g., affecting daily life or requiring therapeutic intervention). 10\. Subjects who have previously received zorifertinib or its active pharmaceutical ingredient. 11\. Known hypersensitivity to zorifertinib's active ingredients, excipients, or drugs with similar chemical structures or classes. 12\. Subjects with other comorbid diseases or factors that, in the investigator's judgment, would pose excessive risk to the subject upon participation in the clinical trial.