High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

Inclusion Criteria:

• Histological or cytological localization is NSCLC;

• confirmed EGFR exon 19 deletion mutation(19del) or EGFR exon 21L858R mutation (L858R) or EGFR exon 20 T790M mutation (T790M)）;

• Clinical diagnosis of meningeal aggravation: clinical symptoms of intracranialhypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebralMRI diagnosis of meningeal aggravation) or cerebrospinal fluid cytologyconfirmation;

• for patients with symptoms who are considered to need temporary brain local.Treatment of cough receiving adrenal corticosteroids must be kept stable or reponsefor at least 1 week before the first trial of the drug preparation;

• Newly diagnosed meningeal metastasis, including meningeal metastasis after previousbrain surgery and/or local radiotherapy for solid metastatic disease;

• Patients did not received systemic treatment after diagnosed meningeal metastases.

• Obtain informed consent signed by the patient's legal representative;

• Aged ≥18 years and ≤75 years;

• Eastern Tourism Cooperation Group (ECOG) Physical condition evaluation 0-1;

• Life expectancy ≥12 week;

• Able to follow the requirements of the study protocol and confirmation procedures,and able to accept cranial wall medications;

• contraception.

Exclusion Criteria:

• Mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as themain pathological type;

• history of hypersensitivity reaction to active or inactive excipients offurmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or classto the investigational drug;

• Currently participating in an interventional clinical trial, or having receivedother study drugs or study devices within 4 weeks before the first study drug;

• Patients who have received solid organ or blood system transplantation;

• Patients with severe intracranial hypertension symptoms that cannot be relieved bydiscontinuation of dexamethasone and/or glycol treatment, or patients in intensivecare;

• Ensure control of the patient's symptomatic pericardial, peritoneal, and pleuraleffusions;

• History of cancer in the last five years Other malignancies or a history of othermalignancies;

• Recent active digestive events, such as duodenitis, ileitis, intestinal perforation,intestinal catheters, or other conditions that may cause gastrointestinal tract orperforation; or refractory vomiting, chronic gastrointestinal disease, inability toswallow study drugs, or previous colorectal cancer resection that prevents adequatedrug absorption;

• The patient has a physique that is prone to Japanese language learning or has activeJapanese language learning; Central squamous cell carcinoma or Patients at greaterrisk for hemoptysis; Any diamond event ≥ CTCAE grade 3, presence of open wounds,injuries or fractures in the 28th century before the first creation; if in the firstAsthma was accepted 28 days before the organization meeting, the wound treatmentshould be evaluated by the interval period;

• History of arterial thromboembolism within the last 6 months, including vascularcerebral accident, myocardial infarction, transient cerebral contemplation;

• History of grade 4 venous thrombosis within the last 6 months, including fireembolism;

• The presence of any severe or uncontrolled systemic evidence, includingdifficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/ordiastolic blood pressure ≥100 mmHg), uncontrolled diabetes, etc.;

• Active infections include, for example, hepatitis B, hepatitis C, and humanimmunodeficiency virus (HIV) infections (including those requiring intravenoustherapy, active hepatitis B infection includes patients with positive hepatitis Bsurface test based on serological assessment and hepatitis B virus DNA >1000copies/ml);

• previous history of interstitial lung disease, drug-induced interstitial lungdisease, pneumonitis requiring steroid therapy, or any evidence of activeinterstitial lung disease;

• The first 28-day inspection of the drug preparation showed Lack of adequate bonemarrow reserve or organ function （Within 2 weeks before blood test, No bloodtransfusion or blood products, granulocyte colony-stimulating factor or otherhematopoietic stimulating factors were used for repair）:

• Absolute neutrophil count <1.5 × 109/L; continuous count <100×109/L; hemoglobin <90 g/L;

• Alanine aminotransferase > 2.5 times Upper limit of normal value (Upper limitof normal）; Aspartate aminotransferase>2.5 times ULN; Total bilirubin>1.5 timesULN; or liver transplant patients with AST and/or ALT > 5× ULN;

• Albumin <30 g/L;

• Serum creatinine >1.5 times ULN, and Creatinine clearance <50 mL/min （Measuredor calculated by Cockcroft and Gault formula);

• International normalized ratio (INR) > 1.5,Partially activated zymogen time （APTT>1.5 times Upper limit of normal;

• Urine protein ≥++, and 24-hour protein >2.0g;

• Any of the following Bishop criteria:

• Clinically significant resting electrocardiogram rhythm, respiratory, ormorphological abnormalities, such as left bundle branch block, third-degreemyocardial insufficiency, and second-degree myocardial insufficiency, within 28days before the first study drug perfume;

• Possibility Interphase Factors that increase the risk of prolonged orarrhythmic events, such as heart failure, congenital long Quantum DotsSyndrome, long Quantum Dots Family history or first-degree relatives 40 Suddendeath due to coma or known prolonged Quantum Dots Any sudden or difficult tofully compensate low potassium tariffs, low tariff tariffs, and lowtariff-to-tariff tariffs during the period;

• Left ventricular ejection fraction (LVEF)Left ventricular ejectionfraction）<50%, recent History of myocardial infarction, severe or unstableangina, or coronary artery bypass grafting within the past month or heartfailure≥ New York Heart Association (New York Heart Association (NYHA) 2 class;

• Pregnancy or breastfeeding.