Zorifertinib With Osimertinib for NSCLC With Meningeal Progression

Inclusion Criteria: For inclusion in the study, patients must meet all of the following criteria. 1. The patient or the guardian is required to understand and sign the informed consent form of this study. 2. During the screening period, subjects must have a previous histological or cytological diagnosis of NSCLC with a sensitising EGFR mutation (including L858R and/or Exon19Del). 3. Only patients who have developed meningeal progression after osimertinib treatment (at a standard dose of 80 mg QD; if the dose is 160 mg QD, it must be reduced to 80 mg QD for at least 1 week before receiving study treatment) (new-onset meningeal progression, or patients with existing meningeal progression that is poorly controlled using osimertinib combined with available conventional treatment \[CNS symptoms not relieved or CSF cytology not turning negative\], but the available conventional treatment must be washed out for at least 4 weeks) and have no extracranial progression are allowed to be enrolled. 4. Subjects with leptomeningeal metastases should have the positive results of cerebrospinal fluid (CSF) cytology. Subjects with negative CSF cytology but highly suspected of leptomeningeal metastases in combination with CSF biochemical test and brain or spinal cord MRI imaging examination are allowed to be enrolled into the study. 5. Subjects with meningeal progression and brain parenchyma progression are allowed to be enrolled. 6. Subjects must have at least one repeatedly evaluable, measurable target lesion (intracranial and/or extracranial) according to mRECIST 1.1 criteria or a repeatedly evaluable lesion according to RANO-LM criteria. 7. Subjects must be ≥ 18 years old before signing the informed consent form (ICF). 8. If there are neurological symptoms, the following conditions must be met: Able to take and swallow oral medication; No need to increase the hormone dose to enhance control of central nervous system symptoms for at least 1 week before study treatment. If a patient is taking hormone for the purpose of treating endocrine dysfunction or tumor-related symptoms (not central nervous system-related), the dose must be stable or reduced within 5 days before the study medication. Note: The hormone dose should be stable 5 days before the baseline brain MRI. 9. All toxicities related to anti-tumor therapy (including radiotherapy) must have resolved to ≤ Grade 1 (CTCAE 5.0, it is sufficient for neurotoxicity related to platinum treatment to resolve to ≤ Grade 2 \[CTCAE\]) before starting the study treatment. Patients with alopecia of any grade are allowed to be enrolled. 10. The screening period examination of patients must meet the followings: * Neutrophil count ≥ 1.5 x 109/L * Platelet ≥ 100 x 109/L * Hemoglobin ≥ 9 g/dL * Blood creatinine ≤ 1.5 x ULN, or creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min * Total bilirubin ≤ 1.5 x ULN (for patients with Gilbert's syndrome or metastases to liver, ≤3 x ULN is acceptable) * Glutamic-oxaloacetic transferase ≤ 2 x ULN (for patients with metastases to liver, ≤ 3 x ULN is acceptable) * Glutamic-pyruvic transaminase ≤ 2 x ULN (for patients with metastases to liver, ≤ 3 x ULN is acceptable) 11. The estimated survival time of subjects is ≥ 6 weeks. 12. Karnofsky Performance Status (KPS) scale score ≥ 60. Exclusion Criteria: Patients must not enter the study if any of the following exclusion criteria is met: 1. Subjects who plan to receive brain radiotherapy or intrathecal injection during the period from signing ICF to study medication. 2. Radiotherapy history within 28 days before study drug administration is not allowed for enrollment, and palliative radiation to the skeleton occurring within 14 days before study drug administration is also not allowed for enrollment. 3. Subjects who have undergone major surgery (e.g. intrathoracic, intraperitoneal or pelvic surgery) within 4 weeks prior to the first dose of study treatment or who have not yet recovered from the side effects associated with such surgery are not allowed to be enrolled. 4. In addition to NSCLC, there are other malignant tumors, or a history of other malignant tumors within 5 years, except for the following cases: Complete resection of skin basal cell and squamous cell carcinoma and radical resection of any type of carcinoma in situ. 5. Suffering from clinically significant and uncontrollable cardiac disorder and/or heart-related events within 6 months, such as: (1) Unstable angina within 6 months before the screening period; (2) Myocardial infarction within 6 months before the screening period; (3) Documented history of heart failure (NYHA Class III-IV) or left ventricular ejection fraction (LVEF) \< 50%; (4) Uncontrollable hypertension: systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, with or without antihypertensive drug treatment; the drugs are allowed to be adjusted before the screening period; (5) Ventricular arrhythmia; (6) Supraventricular or sinus arrhythmias but difficult to control with drugs; (7) Arrhythmias that cannot be controlled by other drugs; (8) QTcF \>470 ms (mean value of three readings corrected using the Fridericia formula) during the screening period. (9) The patient has any factors that increase the risk of QTc prolongation or arrhythmic events, such as electrolyte disturbances, including: Grade 2 or higher hypokalemia according to CTCAE (electrolyte disturbances should be corrected to ≤Grade 1 according to CTCAE and documented before the first dose); heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under the age of 40, or any concomitant medication known to prolong the QT interval and lead to torsades de pointes. 6\. Suffering from gastrointestinal disorders or serious impairment of gastrointestinal function, which may significantly affect drug absorption (e.g. ulcerative diseases, uncontrollable nausea, or