This is a phase II, Open-Label, Multicenter, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined with Pemetrexed/ Carboplatin in Patients with Brain Metastases of Non-squamous Non-small Cell Lung Cancer. The primary end point is PFS, and secondary endpoint is ORR, OS, DoR and Neurocognitive impairment. during the study, the exploratory objectives including (1) PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment (2) Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1 and RANO-BM

Inclusion Criteria:

Disease-related inclusion criteria:

1. Histologically confirmed metastatic (Stage IV) not amenable to curative surgery or radiotherapy, non-squamous NSCLC according to American Joint Committee on Cancer (AJCC), 8th Edition.

2. Radiographically confirmed brain metastases;

3. No prior systemic treatment for stage IV NSCLC. (Bevacizumab administered for improving radiation-induced encephaledema during irradiating intracranial lesions is not considered as systemic therapy for stage IV NSCLC)

4. Patients with asymptomatic BM or symptoms can be controlled by low dose corticosteroids (≤ 10 mg/day of prednisone or equivalent) or antiepileptics drugs;

5. Patients with previous local treatment to BMs should be stable and suitable to receive the systemic treatment;

6. ECOG PS: 0 ~ 1

7. Extracranial measurable target lesions (per RECIST v1.1)

8. Life expectancy ≥ 3 months

   Have adequate hematology, clinical chemistry, and organ function as indicated by the following laboratory values (confirmed within 7 days prior to the first dose):

9. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L.

10. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × upper limit of normal [ULN].

11. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

12. Serum total bilirubin ≤ 1.5 × ULN (total bilirubin must be < 3 × ULN for patients with Gilbert's syndrome).

13. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or AST and ALT ≤ 5 × ULN for patients with liver metastases.

    General inclusion criteria:

14. Able to provide written ICF signed by patient or by his/her legally authorized representative or guardian and can understand and agree to comply with the study protocol and follow-up procedures.

15. Male or female, aged 18 ~ 75 years on the day of signing ICF. Female patients of childbearing potential and non-sterile male patients must be willing to use a highly effective method of birth control for the duration of the study and for at least 120 days after the last dose of tislelizumab.

Exclusion Criteria:

Disease-related exclusion criteria:

1. Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints inhibitors.

2. Received prior systemic chemotherapy for advanced disease.

3. Have EGFR mutation or ALK gene translocation.

4. Patients iwith BMs that have received systemic treatment with corticosteroids (>10 mg/day of prednisone or equivalent) or other drugs to relieve or prevent symptoms of BMs.

5. Patients with intracranial metastases that are locally amenable.

6. Have received any approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor) within 4 weeks prior to the first dose of study drug.

7. Have clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or abdominal tapping for drainage within 2 weeks prior to the first dose of study drugs.

8. Active leptomeningeal metastasis.

   Exclusion criteria related to study drugs:

9. History of allergic reactions to any study drugs and their excipients.

10. Creatinine clearance (Ccr) < 45 mL/min.

11. Patients with active viral hepatitis that requires treatment as judged by the investigator: a. chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (The HBV DNA test will be performed only for patients who have a positive antibody to hepatitis B core antigen (anti-HBc antibody) test); b. patients who have positive hepatitis C virus (HCV) RNA results (The HCV RNA test will be performed only for patients testing positive for HCV antibody).

12. Active autoimmune diseases that requires systemic treatment and may impact study treatment as assessed by investigator.

13. Any condition that required extensive chronic treatment with either corticosteroids or any other immunosuppressive medications that may impact study treatment as assessed by investigator.

    General exclusion criteria:

14. Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc.; 1) Serious infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; 2) Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.

15. Major surgery requiring general anesthesia within 4 weeks before first dose.

16. Underlying medical conditions or alcohol or drug abuse or dependence that are to be unfavorable for the administration of study drugs or may have affected the interpretation of the results or rendered the patient at high risk from treatment complications.

17. Concurrent participation in another therapeutic clinical study. Female patients who are pregnant, breastfeeding, or males and females patients planning to have child during the study.