Sintilimab Combined With Bevacizumab for Brain Metastases From Non-small Cell Lung Cancer

Inclusion Criteria:

1. Patients with NSCLC confirmed by histology or cytology;

2. Patients with asymptomatic brain metastasis or brain metastasis whose symptoms ofintracranial hypertension have been alleviated after dehydration treatment should keepthe clinical stable state for at least 2 weeks.For patients requiring hormonedehydration therapy, hormone therapy should be discontinued 3 days before the firstdose of the study drug.

3. Appraisable disease, the diameter of at least one measurable lesion in the brain mustbe 5mm;

4. The detection results of tumor tissue biomarkers should meet the following conditionssimultaneously: EGFR has no sensitive mutation;ALK rearrangement negative;for nevertreated patients, they also needed to meet PD-L1 >50% or TMB>12Mut/Mb (second-generation sequencing).

5. Adult patients (≥ 18 years and ≤75 years). ECOG Performance Status 0 or 1 Lifeexpectancy of at least 12 weeks.,Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count (ANC) ³1.5 x 109/L, platelets ³ 100 x 109/L. Total bilirubin £ 1.5 x upper limit ofnormal (ULN). ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULNin case of liver metastases. Creatinine clearance ³ 60ml/min (calculated according toCockcroft-gault formula).

6. Ability to follow study and follow-up procedures;

7. Prior to the implementation of any trial-related procedures, a written informedconsent shall be signed.

Exclusion Criteria:

1. Mixed non-small cell and small cell carcinoma;

2. Brain metastasis with hemorrhage;

3. Currently participating in interventional clinical research and treatment, orreceiving other research drugs or using research instruments within 4 weeks before thefirst dose;

4. Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugsor drugs targeting another stimulation or synergistic inhibition of T cell receptors (e.g., CTLA-4, CD137);

5. Received solid organ or blood system transplantation;

6. Received >30GY pulmonary radiotherapy 6 months before the first dose;

7. Active autoimmune diseases requiring systemic treatment (such as the use ofdisease-relieving drugs, corticosteroids or immunosuppressants) occurred within 2years before the first dose.Alternative therapies (such as thyroxine, insulin, orphysiological corticosteroids for adrenal or pituitary insufficiency) are notconsidered systemic;

8. Received systemic glucocorticoid therapy or any other form of immunosuppressivetherapy within 7 days before the first dose of the study or diagnosed asimmunodeficiency;a physiological dose of glucocorticoid (10 mg/ day of prednisone orequivalent) is permitted;

9. History of non-infectious pneumonia requiring glucocorticoid therapy or currentinterstitial pulmonary disease was found within 1 year before the first dose;

10. History of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibodypositive)

11. Untreated active hepatitis;

12. History of hemoptysis within 3 months prior to selection, that is, at least 1/2teaspoon of blood was coughed up;

13. Imaging showed signs of tumor invasion into the great vessels.The investigator orradiologist must rule out patients whose tumors have completely approached, wrapped,or invaded the intravascular space of the great vessels

14. Serious uncontrolled coagulation disorder or thrombi-embolic complications within 6months prior to study start or history of serious bleeding complications.

15. Major surgical procedures within 4 weeks prior to study entry.

16. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior tothe first bevacizumab infusion.

17. Non-healing wound, active peptic ulcer or bone fracture.

18. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscesswithin 6 months of enrollment