Efficacy and Resistance Mechanisms of IP in NSCLC With Leptomeningeal Metastases

Inclusion criteria

• Age ≥ 18 years.
• Histopathology or cytology confirmed metastatic non-small cell lung cancer with leptomeningeal metastasis after TKI resistant.
• EGFR mutant, ALK fusion, ROS1 fusion, and other oncogenic alterations including RET fusion, BRAF mutation, NTRK fusion, KRAS mutation was confirmed by an accredited local laboratory.
• Adequate bone marrow hematopoiesis and organ function
• Agree to receive intrathecal pemetrexed
• ECOG 0 - 2.
• Predicted survival ≥ 12 weeks.

Exclusion criteria

• Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
• 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.
• Presence of spinal cord compression or meningeal metastasis.
• History of other malignant tumors within 2 years.
• Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• 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.
• Heart-related diseases or abnormalities
• 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.
• Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• Live vaccine was given 2 weeks before the first medication.
• Women who are breastfeeding or pregnant.
• Hypersensitivity to the test drug and the ingredients.
• Other conditions assessed by the investigator to be unsuitable for participation in the study.