Efficacy and Safety of Use of Platinum Based Doublet Chemotherapy Plus Antiangiogenesis and Immune Checkpoint Inhibitors in Patients With Advanced Non-squamous Non-small Cell Lung Cancer

The purpose of this study is to explore the efficacy and safety of Use of Platinum Based Doublet Chemotherapy Plus Antiangiogenesis and Immune Checkpoint Inhibitors in Patients With Advanced Non-squamous Non-small Cell Lung Cancer


Eligibility Criteria:
Inclusion Criteria:

1. Voluntarily sign informed consent;
2. Non-squamous non-small cell lung cancer, newly diagnosed or previously not treated with systemic chemotherapy and / or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors treatment;
3. Aged 18-75 years;
4. Eastern Cooperative Oncology Group (ECOG) score ≤ 2;
5. Survival is expected to exceed 12 weeks ;
6. Patients had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded)

Exclusion Criteria:

If any of the following criteria is met, the subject shall be excluded:

1. Squamous cell carcinoma (including adenosquamous carcinoma) and small cell lung cancer (including small cell carcinoma and non-small cell mixed lung cancer);
2. In the past 2 weeks, there have been systematic anti-tumor treatment including chemotherapy (including thoracic chemotherapy), radiotherapy (excluding radiotherapy of metastatic lesions outside the thoracic radiation field), targeted therapy, immunotherapy and biotherapy;
3. The subject had received anti-vascular endothelial growth factor (VEGF) small molecule tyrosine kinase inhibitors or monoclonal antibodies in the past 4 weeks;
4. Laboratory results:

   * White blood cell count \<3 × 109 / L, neutrophil count \<1.5 × 109 / L, platelet \<75 × 109 / L, or hemoglobin \<8g / dL;
   * Coagulation abnormalities (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or activated partial thromboplastin time (APTT) \> 1.5 ULN), with bleeding tendency or being treated with thrombolysis or anticoagulation;
   * Serum total bilirubin ≥1.5 ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 ULN in the absence of liver metastases; ALT or AST ≥5 ULN in liver metastases;
   * Serum albumin \<30g / L;
   * Serum creatinine ≥ 1.5 ULN or creatinine clearance \<40ml / min; • Urine routine urinary protein ≥ ++, or 24 hours urine protein ≥ 1.0 g;
5. Heart disease with significant clinical symptoms, such as: congestive heart failure, coronary heart disease with symptom, arrhythmia hardly be controlled by drugs, myocardial infarction in 6 months, or heart failure;
6. Imaging (CT or MRI) showed a tumor lesion 5 mm away from the large vessels, or the presence of invasive central vasculature of the central tumor; imaging (CT or MRI) showed significant cavitation or necrosis of the lung tumor; Other diseases that may cause haemoptysis;
7. Imaging (CT or chest radiograph) showed significant pneumothorax, fluid pneumothorax;
8. Obvious cough blood in 6 months, or daily hemoptysis amounted to half a teaspoon (2.5ml) or more;
9. Significant bleeding symptoms or with definite bleeding tendency within 12 months before randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, occult blood ++ and above, intracerebral hemorrhage, vasculitis, or with congenital or acquired coagulopathy disorders;
10. Thrombosis, cancer thrombosis (including arteriovenous thrombosis, tumor thrombus, pulmonary embolism, transient ischemic attack, etc.) occurred within 12 months;
11. There are gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative colitis and other gastrointestinal diseases or other diseases may cause gastrointestinal bleeding or perforation;
12. Severe respiratory diseases, or need long-term oxygen, corticosteroid treatment of diseases such as chronic obstructive pulmonary disease, interstitial lung disease and respiratory failure;
13. Patients with uncontrolled central nervous system metastasis;
14. There are serious uncontrolled systemic diseases, such as nephrotic syndrome, infection, poorly controlled diabetes;
15. Patients with active HIV（human immunodeficiency virus）, HBV（hepatitis B virus）, or HCV（hepatitis C virus） infection;
16. Patients had undergone surgery (\<28 days) or did not heal completely, or had other unhealed wounds before the study;
17. Patients known to be allergic to bevacizumab or any of the components of the drug;
18. Pregnant or lactating female patients, or unwilling to take contraceptive measures of reproductive age patients (including men);
19. There is a serious psychological or mental abnormality, or lack of compliance;
20. The investigator determines other circumstances that may affect the conduct of clinical studies and the determination of findings;
21. Participants with an active, known or suspected autoimmune disease;
22. Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first treatment;
23. Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug related pulmonary toxicity.