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

Study Overview
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Brief Summary
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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

Official Title
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A Prospective of 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

Conditions
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Advanced Non-squamous Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Antiangiogenesis Agents
* Drug: Immune checkpoint inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily sign informed consent; 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; Aged 18-75 years; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; Survival is expected to exceed 12 weeks ; 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: Squamous cell carcinoma (including adenosquamous carcinoma) and small cell lung cancer (including small cell carcinoma and non-small cell mixed lung cancer); 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; The subject had received anti-vascular endothelial growth factor (VEGF) small molecule tyrosine kinase inhibitors or monoclonal antibodies in the past 4 weeks; 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; 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; 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; Imaging (CT or chest radiograph) showed significant pneumothorax, fluid pneumothorax; Obvious cough blood in 6 months, or daily hemoptysis amounted to half a teaspoon (2.5ml) or more; 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; Thrombosis, cancer thrombosis (including arteriovenous thrombosis, tumor thrombus, pulmonary embolism, transient ischemic attack, etc.) occurred within 12 months; There are gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative colitis and other gastrointestinal diseases or other diseases may cause gastrointestinal bleeding or perforation; Severe respiratory diseases, or need long-term oxygen, corticosteroid treatment of diseases such as chronic obstructive pulmonary disease, interstitial lung disease and respiratory failure; Patients with uncontrolled central nervous system metastasis; There are serious uncontrolled systemic diseases, such as nephrotic syndrome, infection, poorly controlled diabetes; Patients with active HIV（human immunodeficiency virus）, HBV（hepatitis B virus）, or HCV（hepatitis C virus） infection; Patients had undergone surgery (<28 days) or did not heal completely, or had other unhealed wounds before the study; Patients known to be allergic to bevacizumab or any of the components of the drug; Pregnant or lactating female patients, or unwilling to take contraceptive measures of reproductive age patients (including men); There is a serious psychological or mental abnormality, or lack of compliance; The investigator determines other circumstances that may affect the conduct of clinical studies and the determination of findings; Participants with an active, known or suspected autoimmune disease; Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first treatment; Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug related pulmonary toxicity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>antiangiogenesis 7.5mg/Kg q3w+pemetrexed 500mg/m2 q3w+ platinum 75mg/m2 q3w | Drug: Antiangiogenesis Agents<br>* antiangiogenesis agents plus chemotherapy as first line treatment<br>|
| Group B<br>immune checkpoint inhibitors 200mg q3w+pemetrexed 500mg/m2 q3w+platinum 75mg/m2 q3w | Drug: Immune checkpoint inhibitor<br>* immune checkpoint inhibitor plus chemotherapy as first line treatment<br>|
| Group C<br>antiangiogenesis 7.5mg/Kg q3w+immune checkpoint inhibitors 200mg q3w+pemetrexed 500mg/m2 q3w+platinum 75mg/m2 q3w | Drug: Antiangiogenesis Agents<br>* antiangiogenesis agents plus chemotherapy as first line treatment<br>Drug: Immune checkpoint inhibitor<br>* immune checkpoint inhibitor plus chemotherapy as first line treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | ORR of treatment | one year |