Combining Tislelizumab, Endostatin, and Chemotherapy for Advanced Lung Cancer

1. Have fully understood the study and voluntarily signed the informed consent;
2. Age 18-75 years old, gender is not limited;
3. Histologically confirmed Stage III initial unresectable squamous or non-squamous non-small cell lung cancer (AJCC Stage 8th edition)

   \- Unresectable stage III NSCLC mainly refers to imaging or lymph node pathological evidence: Multiple metastases of ipsilateral mediastinal lymph nodes fused into masses or multisite metastases (IIIA: T1-2N2 or IIIB: T3-4N2); metastases to the contralateral hilar, mediastinal lymph nodes, or to the same, contralateral scalene, or supraclavicular lymph nodes (IIIB: T1-2N3, IIIC: T3-4N3); lesion invasion of important organs (including diaphragm, mediastinum, great blood vessels, trachea, recurrent laryngeal nerve, esophagus, or satellite nodules in different pulmonary lobes on the same side of the primary tumor, resulting in clinician determination that R0 resection could not be performed) (IIIA: T4N0-1); Determination of o N2/N3 lymph node involvement: PET-CT was used to confirm lymph node status. In cases where PET-CT is insufficient to determine lymph node staging (for example, lymph node diameter \<2cm), pathologic confirmation (EBUS/EUS/ thoracoscopic/mediastinoscopy or fine needle aspiration biopsy) is performed by the investigator to select appropriate lymph nodes to determine the staging.

   Clinical evaluation of unresectable Stage III NSCLC: Other clinicians determine that R0 resection is not feasible or that a total lung resection is required to achieve R0 resection.
4. At least 1 measurable lesion as defined by RECIST v1.1;
5. ECOG score 0-1;
6. Eligible for platinum-containing double-drug chemotherapy.
7. Good organ function;

   • Patients have not received blood transfusion or growth factor support therapy ≤ 14 days prior to sample collection during the screening period and: Absolute neutral cell count (ANC) ≥1.5 x 109/L
   * Platelet ≥100 x 109/L
   * Hemoglobin ≥90 g/L

     • Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula)
   * Patients scheduled to receive cisplatin: creatinine clearance ≥ 60 mL/min
   * Patients scheduled to receive carboplatin: creatinine clearance ≥ 45 mL/min

     * Serum total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert\'s syndrome must have total bilirubin \< 3 × ULN)
     * AST and ALT≤ 2.5 x ULN
     * Patients who did not receive anticoagulant therapy: International standardized ratio or activated partial thromboplastin time ≤ 1.5 × ULN
     * Albumin ≥25 g/L (2.5 g/dL).
8. Willing and able to comply with study plan visits, treatment plans, laboratory tests and other study procedures;
9. The total amount of lung function, as assessed by the surgeon, is sufficient to withstand the proposed pneumonectomy;
10. Women of childbearing age must take a serum pregnancy test within 3 days before the first medication, and the result is negative. Female subjects of reproductive age and male subjects whose partners are women of reproductive age must agree to use highly effective methods of contraception during the study period and for 120 days after the last dose of the study drug

Exclusion Criteria:

1. Patients with known EGFR gene mutation, ALK rearrangement, ROS-1 fusion, RET fusion, HER-2 mutation, MET mutation, and non-squamous cell carcinoma with unknown driver gene status;
2. Previous treatment for current lung cancer, including radiotherapy and all systemic antitumor agents, including chemotherapy, immunotherapy, targeted therapy or antiangiogenic therapy.
3. Patients with large cell neuroendocrine carcinoma (LCNEC) components and non-small cell lung cancer with mixed small cell components.
4. Patients received other approved systemic immunomodulators (including, but not limited to, interferon, interleukin 2, tumor necrosis factor, thymus pentapeptide, and thymofasin) within 4 weeks prior to initial administration.
5. In the course of treatment, researchers determined that patients\' tumors were more likely to invade important blood vessels and cause fatal bleeding.
6. Clinically significant hemoptysis (more than 50ml of hemoptysis per day), or clinically significant bleeding symptoms or significant bleeding tendency (such as gastrointestinal bleeding, gastric ulcer bleeding, gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occulted blood ++ or above baseline, or vasculitis) within 3 months before the study.
7. Any Chinese herbs used for cancer control were used within 14 days prior to the first administration of the study drug.
8. Have received live vaccine within 30 days before the first dose. Including but not limited to the following: mumps, rubella, measles, varicella/shingles (chickenpox), yellow fever, rabies, BCG and typhoid vaccine (inactivated virus vaccine allowed); Live or attenuated vaccine is expected to be required during the study period or within 5 months after the last dose.
9. For any condition requiring systemic treatment with corticosteroids (prednisone or equivalent \>10 mg/ day) or other immunosuppressive agents within 14 days prior to the first administration of the study drug, the investigator assessed the patient as having an impact on the study treatment.
10. Active autoimmune diseases requiring systemic treatment in patients assessed by the investigator as having an impact on investigational treatment.
11. Patients with interstitial lung disease, non-infectious pneumonia, or other diseases that are not under control, including diabetes, pulmonary fibrosis, acute lung disease, etc., that the investigators have assessed as having an impact on the study treatment.
12. Patients with a history of major diseases or clinical manifestations that may affect the function of organ systems and are assessed by the investigator as having implications for the study and treatment.
13. Study severe chronic or active infections (including tuberculosis) requiring systemic antimicrobial, antifungal, or antiviral treatment ≤14 days before the first administration of the drug.
14. Uncontrolled active hepatitis B (defined as positive HBV surface antigen \[HBsAg\] test results during screening and HBV-DNA test values higher than the upper limit of normal values in the laboratory of the research center; (Participants with HBV-DNA levels \< 500 IU/mL within 28 days prior to enrollment, who have received local standard antiviral therapy for at least 14 days and who are willing to continue antiviral therapy during the study period may be enrolled); Subjects with active hepatitis C (defined as positive HCV surface antibody \[HCsAb\] test results during screening, positive HCV-RNA);
15. Known human immunodeficiency virus (HIV) infection (known HIV antibody positive);
16. Grade III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias;
17. Any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to treatment;
18. Concurrent participation in another therapeutic clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study.
19. Medical history or evidence of disease that may interfere with the test results, prevent participants from participating fully in the study, abnormal treatment or laboratory test values, or other conditions that the investigator considers unsuitable for enrollment. The Investigator considers that there are other potential risks that are not suitable for participation in the study.