A Study of TQB2450 Injection Plus Chemotherapy Followed by TQB2450 Plus Anlotinib Versus Tislelizumab Plus Chemotherapy Followed by Tislelizumab in the Treatment of First-line Non-squamous Non-small Cell Lung Cancer(NSCLC).

Inclusion Criteria:

• 1 According to the 8th edition of the International Association for the Study of LungCancer and the American Joint Committee on Cancer Classification, the TNM staging oflung cancer is locally advanced (stage ⅢB/ⅢC), metastatic or recurrent ( Stage IV)NSCLC patients.
• 2 Between the ages of 18-75 years (calculated based on the date of signing ICF); maleor female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survivaltime ≥ 3 months.
• 3 According to the RECIST 1.1 standard, there is at least one measurable lesion. Ifthe measurable lesion is located in the radiotherapy area, it should be clearlydefined as a progressive state.
• 4 Patients who have not received systemic anti-tumor therapy for advanced, recurrentor metastatic diseases in the past. For those who have received adjuvant chemotherapyin the past, the interval between the recurrence time and the last adjuvantchemotherapy should be at least 6 months; The interval between the end of previousradiotherapy for chest and this treatment should be more than 6 months, and theinterval between palliative radiotherapy for chest and this treatment should be morethan 7 days.
• 5 Tumor tissue sections that have not undergone radiotherapy at or after the diagnosisof advanced or metastatic NSCLC must be provided. Tumor tissue samples must bearchived samples or freshly obtained samples within 12 months before randomization.
• 6 For non-squamous NSCLC, patients with no EGFR sensitive mutations, ALK fusion, ROS1fusion
• 7 The function of main organs are well and meet the following standards:
• 8 a. Routine blood examination standards (without blood transfusion or correction withhematopoietic stimulating factor drugs within 14 days before screening): i. Absoluteneutrophil count (ANC) ≥1.5×109 /L; ii. Platelets ≥100×109 /L; iii. Hemoglobin ≥90g/L. b. The blood biochemical examination shall meet the following standards: i. Totalbilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (Patients with Gilbert syndrome ≤ 3 × ULN); ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN. If it is accompanied by liver metastasis, ALT and AST≤5×ULN; 8.iii.Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gaultglomerular filtration formula ≥60 mL/min; iv. Serum albumin (ALB) ≥30g/L. c. Urineroutine examination standard: urine routine indicates urine protein <++; if urineprotein ≥++, it is necessary to confirm that the 24-hour urine protein quantitative ≤1.0 g. d. Blood coagulation test standards: prothrombin time (PT), activated partialthromboplastin time (APTT), international normalized ratio (INR)≤1.5×ULN (noanticoagulant therapy). e. Thyroid Stimulating Hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should beexamined. If T3 and T4 levels are normal, it can be selected. f. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%. g. 12-lead ECG evaluation: QTc<450ms (male), QTc<470ms (female).
• 9 Women of childbearing age should agree to use effective contraceptive measuresduring the study period and 6 months after the end of the study, and have a negativeserum pregnancy test within 7 days before the study enrollment; men should agree tothe study period and 6 months after the end of the study period Effectivecontraceptive measures must be used internally.
• 10 The subjects voluntarily joined the study, signed the informed consent form, andhad good compliance.

Exclusion Criteria:

• 1 Tumor disease and medical history:

1. Brain metastases without local treatment; Note: Subjects who have previouslyreceived brain metastasis therapy and meet all the following criteria canparticipate in this study: i. Only supratentorial and cerebellar metastases; ii.The condition needs to be stable for ≥4 weeks and no new brain metastases orbrain metastases are found Expanded imaging evidence; iii. The subject must havestopped corticosteroids/dehydrator for at least 2 weeks before starting to usethe trial drug;
2. There are midbrain, pons, medulla oblongata, spinal cord and meningealmetastases；
3. Other malignant tumors appeared or were present within 3 years. The following twocases can be included: other malignant tumors treated by single operation haveachieved 5-year Disease-free survival (DFS) in a row; The cured cervicalcarcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basementmembrane)];
4. Central type, cavity squamous cell carcinoma (primarily in the main bronchus andaround the hilar);Imaging shows that the tumor invades large blood vessels or isunclearly separated from the blood vessels, or the investigator judges that thetumor is likely to invade important blood vessels and cause fatal bleeding duringthe subsequent study(The major vessels in the chest include pulmonary aorta, leftpulmonary artery, right pulmonary artery, four pulmonary veins, superior venacava, inferior vena cava and aorta);
5. Severe bone injury caused by tumor bone metastasis, including pathologicalfracture of weight-bearing bone and spinal cord compression that occurred within 6 months or is expected to occur in the near future(Such as spine, pelvis, femur,tibia, phalanges, calcaneus, etc.);
6. Patients with serous cavity (thoracic cavity, abdominal cavity, or pericardialcavity) that require repeated drainage to relieve clinical symptoms (asdetermined by the investigator), or who have received drainage of serous cavityeffusion for the purpose of treatment within 2 weeks before treatment.

• 2 Previous anti-tumor treatments:

1. Received the treatment of proprietary Chinese medicines with anti-tumorindications specified in the NMPA approved drug instructions within 2 weeksbefore the start of the study treatment(Including compound cantharidin capsules,Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanicaoil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.);
2. Previously received related immunotherapy drugs for programmed death 1 (PD-1),PD-L1, cytolytic T lymphocyte-associated antigen-4 (CTLA-4), etc.;
3. Previous use of anti-angiogenic drugs such as bevacizumab, anlotinib, apatinib,lenvatinib, sorafenib, sunitinib, regorafenib, fruquintinib, etc.;
4. Patients who have been vaccinated with immunomodulatory drugs within 30 daysbefore starting treatment(Such as interleukin-2, thymosin, lentinan, etc.);
5. Failure to recover from the toxicity and/or complications of previousinterventions to CTCAE ≤1, except for hair loss and peripheral neuropathy ≤2;

• 3 Combined diseases and medical history:

1. Liver cirrhosis, active hepatitis*;(Note: active hepatitis (hepatitis Breference: HBV-DNA > 1*103 copy /mL or > 2000IU/mL) when HBsAg is positive.Hepatitis C reference: HCV antibody is positive, and HCV titer detection valueexceeds the upper limit of normal value);
2. Renal abnormalities: i.Renal failure requires hemodialysis or peritonealdialysis; ii.Previous or existing nephrotic syndrome, chronic nephritis.
3. Cardiovascular and cerebrovascular abnormalities： i.Patients with previous orpresent heart failure, degree II or above heart block: ii.Myocardial infarctionor unstable angina, supraventricular or ventricular arrhythmia with clinicalsignificance need treatment or intervention; iii.Vascular embolism andcerebrovascular accident (including transient ischemic attack, cerebralhemorrhage and cerebral infarction) occurred within 9 months（ Prophylactic use ofanticoagulant therapy is allowed for patients with thrombotic tendency orundergoing anticoagulant therapy.) iv.After more than two kinds of drugtreatment, blood pressure control is still not ideal (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg).
4. Gastrointestinal abnormalities: i.Inability to take medications (such asinability to swallow, intestinal obstruction, etc.); ii.A history ofmalabsorption syndrome or other diseases that interfere with gastrointestinalabsorption; iii.Received treatment for active peptic ulcer in the past 6 months; iv.Despite the maximum medical treatment, chronic diarrhea of grade 2 and abovecontinues to occur; v.Other conditions determined by the researcher that maycause gastrointestinal bleeding and perforation.
5. History of immunodeficiency: i.Have a history of immunodeficiency, including HIV positive or other acquired orcongenital immunodeficiency diseases; ii.Active autoimmune disease or history ofautoimmune disease, including but not limited to Crohn's disease, ulcerative colitis,autoimmune hepatitis/enteritis/vasculitis/nephritis, etc. iii.Prepare to undergo or have previously received an organ transplant; iv.Patients whorequire systemic or topical immunosuppressive therapy to achieve immunosuppressive purposesand need to continue to use them within two weeks before randomization (except forglucocorticoid daily dose <10 mg prednisone or other equivalent hormones). Note: Hormone replacement therapy (such as thyroxine, insulin, or physiologicalcorticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is notconsidered as systemic therapy and allowed to be used.

f. Bleeding risk: i.Suffered from bleeding or coagulopathy within 28 days before the startof treatment or was using warfarin, aspirin and other antiplatelet agglutination drugs (except for aspirin ≤100 mg/d preventive drugs); ii.Had hemoptysis >2.5 mL/day in 28 daysbefore the start of treatment; iii.Regardless of the severity, patients with any history ofbleeding or coagulopathy; iv.Received major surgical treatment, open biopsy, etc. within 28days before the start of the study treatment; v.Long-term unhealed wounds or fractures,except for pathological fractures; g. Poor control of type I diabetes or II diabetes (fasting blood glucose (FBG)> 10mmol/L); h. Severe infections within 4 weeks before thestart of study treatment, including but not limited to hospitalization due to bacteremia,severe pneumonia, or other severe infections; subjects with ≥ grade 2 active infectionswithin 4 weeks before the start of study treatment Or fever of unknown cause occurredduring the screening period and before the first administration>38.0℃; i. Past or existingpneumoconiosis, interstitial pneumonia, (non-infectious) pneumonia that requires adrenalcorticosteroid therapy, currently suffering from other types of pneumonia ≥2, or lungfunction tests confirmed severely impaired lung function (Forced Expiratory Volume in thefirst second (FEV1) or diffusing capacity of lung for carbon monoxide(DLCO) or DLCO peralveolar volume (DLCO /VA) accounts for the expected value %<40%) and other objectiveevidence; j. Patients with active tuberculosis within 1 year before enrollment; subjectswith a history of active pulmonary tuberculosis infection 1 year ago must provide clearevidence of cure before enrollment; if tuberculosis is suspected during the screeningperiod, chest radiographs and sputum must be passed Enter the group only after the liquidand clinical symptoms are eliminated; k. Allergies, or a history of severe allergies in thepast, or severe hypersensitivity reactions after receiving other monoclonal antibodytreatments, or known allergies to the ingredients of the study drug excipients; l. Previoushistory of severe mental disorders; m. People with a history of drug abuse, alcohol or drugabuse;

• 4 The end of the previous clinical study (last dose) is less than 4 weeks or the studydrug's 5 half-lives, whichever is shorter.
• 5 Live attenuated vaccine vaccination history within 28 days before randomization orplanned live attenuated vaccination during the study period. Seasonal influenzavaccine for injection is usually an inactivated virus vaccine and is allowed to bevaccinated during the study period.
• 6 Female patients during pregnancy or lactation.
• 7 According to the investigator's point of view, it may increase the risks associatedwith participating in the study, or other severe, acute or chronic medical diseases orlaboratory abnormalities that may interfere with the interpretation of the studyresults, or other reasons that are not suitable for participating in this clinicalstudy.