Immune Checkpoint Inhibitors Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC

Inclusion Criteria: 1. Aged 18-75 years old, male or female; 2. Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis; 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 4; 4. Expected survival time of at least 4 weeks; 5. Oncologist clarification of the potential necessity of receiving systemic therapy for metastatic tumors outside the CNS; 6. Previous radiation therapy, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), which must be completed at least 7 days prior to the start of treatment; 7. Patients who have received approved targeted therapies (EGFR inhibitors, ALK inhibitors, or other targeted therapeutic agents), and other systemic therapies will be allowed to remain on concurrent therapy; concurrent intrathecal therapy with other agents will not be allowed. 8. Laboratory test indicators meet the following criteria: 1. Bone marrow function: hemoglobin (Hb) ≥80g/L; white blood cell count (WBC) ≥lower limit of normal; absolute neutrophil count (ANC) ≥1.5×10\^9 /L; platelet count ≥70×109 /L; 2. Renal function: Cr ≤ ULN (upper limit of normal) × 1.5, endogenous creatinine clearance (Ccr) ≥ 55 ml/min; 3. Liver function: total bilirubin ≤ ULN × 1.5; ALT and AST ≤ ULN × 2.5; (if there is liver metastasis, total bilirubin is not higher than 3 times the upper limit of normal, and transaminases are not higher than 5 times the upper limit of normal); 4. Coagulation function: international normalized ratio of prothrombin time ≤ ULN × 1.5, and partial thromboplastin time within the normal value; 9. Females of child-bearing potential agree to use contraception during the study period and for 6 months after the completion of the study; patients who have had a negative serum or urine pregnancy test within seven days prior to enrollment in the study and who are not breastfeeding; and males agreeing to use contraception during the study period and for 6 months after the completion of the study; 10. Those who have not participated in another drug clinical trial within 4 weeks prior to enrollment; 11. Subjects who can understand the study situation and voluntarily sign the informed consent form; 12. Patients are expected to be compliant and able to follow up on efficacy and adverse events according to protocol requirements. Exclusion Criteria: 1. Diagnosis of other malignant tumors (except carcinoma in situ, basal cell carcinoma, etc.) within the previous 5 years; 2. History of allergy to pemetrexed and ICIs therapy; 3. Any previous intrathecal injection therapy; 4. Rule out differential diagnosis of LM:a. Aseptic meningitis b. Viral meningitis c. Bacterial meningitis; 5. Participation in other clinical trials or observation periods; 6. Clinical conditions that would interfere with the evaluation or interpretation of safety or findings, or impede the understanding of informed consent and compliance with protocol requirements; 7. Presence of any treatment-related toxicity from prior systemic antitumor therapy other than alopecia that does not meet CTCAE grade 1 (based on CTCAE 5.0); 8. Presence of any active autoimmune disease or history of autoimmune disease; immunodeficiency, active tuberculosis, hepatitis B ( hepatitis B virus titer HBV-DNA \<500 IU/ml after treatment and if liver function is normal will be allowed), or positive test for hepatitis C virus. 9. Either disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy; 10. Presence of active infection or serious comorbidities; 11. uncontrolled epilepsy, neurologic failure, or severe neurologic impairment related to treatment; 12. Presence of hereditary or acquired bleeding and thrombotic tendencies; 13. History of severe injury or surgery within 1 month prior to enrollment; 14. Treatment with a live or attenuated vaccine used for the prevention of infectious diseases within 30 days prior to the first administration (injectable seasonal influenza vaccine is permitted); 15. Inability to complete an enhanced MRI; 16. Treatment with immunosuppressive drugs or corticosteroids (\> 10 mg prednisone or equivalent per day) within 14 days prior to enrollment; patients are allowed to receive steroid therapy to control CNS-related symptoms, but the dose must ≤ 5 mg per day of dexamethasone (or equivalent); in the absence of an active autoimmune disease, inhaled or topical steroids and adrenal gland replacement dosing are acceptable; alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are permitted; patients with experimental medications that require premedication with corticosteroids are not restricted; 17. Individuals considered by the investigator to be unsuitable for enrollment.