Intrathecal Pemetrexed Combined With High-dose Furmonertinib and Beva for EGFR-m NSCLC With Leptomeningeal Metastases

Inclusion Criteria:

* 1\. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
* 2\. Age ≥ 18 years.
* 3\. Histopathology confirmed Non-small cell lung cancer.
* 4\. confirmed or probable leptomeningeal metastases according to EANO-ESMO guidelines or known leptomeningeal metastases progression after third generation of EGFR-TKIs failure.
* 5.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
* 6.ECOG 0 - 2.
* 7\. Predicted survival ≥ 12 weeks.
* 8\. Adequate bone marrow hematopoiesis and organ function.

Exclusion Criteria:

* 1\. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
* 2\. Subjects who have received any of the following treatments must be excluded: Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
* 3\. Presence of spinal cord compression.
* 4\. History of other malignant tumors within 2 years.
* 5\. Adverse events (except alopecia of any degree) of CTCAE \> grade 4 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
* 6\. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
* 7\. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
* 8\. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
* 9\. Heart-related diseases or abnormalities
* 10\. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
* 11\. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb Furmonertinib due to previous bowel resection.
* 12\. Live vaccine was given 2 weeks before the first medication.
* 13\. Women who are breastfeeding or pregnant.
* 14\. Hypersensitivity to the test drug and the ingredients.
* 15\. Other conditions assessed by the investigator to be unsuitable for participation in the study.