Study of Tislelizumab for Locally Advanced Non-Small Cell Lung Cancer Following Neoadjuvant Chemotherapy Plus Tislelizumab ± Bevacizumab and Definitive Concurrent Chemoradiation Therapy

Inclusion Criteria: * For inclusion in neoadjuvant therapy, patients should fulfil the following criteria: * Provision of signed, written and dated informed consent prior to any study specific procedures; * Male or female aged 18\~75 years old; * Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced (Stage III) disease; * Without prior chemotherapy, radiotherapy, surgery, targeted therapy or immunotherapy; * A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk; * Life expectancy ≥12 weeks; * World Health Organization (WHO) Performance Status of 0 or 1; * Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients within 14 days before the use of study drug (HCG has a minimum sensitivity of 25 IU/L or equivalent); * Women must be non-breastfeeding * Forced expiratory volume in 1 second (FEV1) ≥800ml * Absolute neutrophil count \>1.5 x 109/L (1500 per mm3) * Platelets \>100 x 109/L (100,000 per mm3) * Haemoglobin≥9.0 g/dL (5.59 mmol/L) * Serum creatinine clearance(CL) \>50 mL/min by the Cockcroft-Gault formula (Cockcroft and -Gault 1976) * Serum bilirubin ≤1.5 x upper limit of normal (ULN). Aspartate Transaminase(AST) and Alanine Transaminase(ALT) ≤2.5 x ULN Exclusion Criteria: * Exclusion criteria for enrolment for neoadjuvant therapy Patients should not enter the study if any of the following exclusion criteria are fulfilled: * Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study; * Mixed small cell and non-small cell lung cancer histology; * Current or prior use of immunosuppressive medication within 28 days before the first dose of Tislelizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for NSCLC is allowed. * Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody; * Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of Tislelizumab; * Active or prior documented autoimmune disease within the past 2 years; * Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis); * History of primary immunodeficiency; * History of organ transplant that requires therapeutic immunosuppression; * The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava) * Bleeding tendency or coagulation disorder * Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months * Uncontrolled hypertension (systolic \> 150mmHg and/or diastolic \> 100mmHg) * Major surgery within 28 days or minor surgery or needle biopsy within 48 hours * Urine protein 3-4+, or 24h urine protein quantitative \>1g * Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction; * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent; * Known history of tuberculosis; * Receipt of live attenuated vaccination within 30 days prior to study entry or within30 days of receiving Tislelizumab; * History of another primary malignancy within 5 years prior to starting Tislelizumab, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study; * Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control; * Any condition that, in the opinion of the investigator, would interfere with evaluation of the Tislelizumab or interpretation of patient safety or study results. * Exclusion criteria for concurrent chemoradiation following neoadjuvant therapy Patients should not enter the concurrent chemoradiation phase if any of the following exclusion criteria are fulfilled: * Patients who develop disease progression and the irradiation dose of normal tissue will exceed the limit as defined in Section 7. * World Health Organization (WHO) Performance Status of 2-4; * Inadequate organ and marrow function as defined below: * Forced expiratory volume in 1 second (FEV1) \<800ml * Absolute neutrophil count \<1.5 x 109/L (1500 per mm3) * Platelets \<100 x 109/L (100,000 per mm3) * Haemoglobin\<9.0 g/dL (5.59 mmol/L) * Serum creatinine CL \<50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) * Serum bilirubin \>1.5 x upper limit of normal (ULN). * Aspartate Transaminase(AST) and Alanine Transaminase(ALT) \>2.5 x ULN * Further exclusion criteria for Tislelizumab consolidation: Patients should not enter the Tislelizumab consolidation if any of the following exclusion criteria are fulfilled: * Patients who have progressed whilst definitive platinum based, concurrent chemoradiation therapy; * Current or prior use of immunosuppressive medication within 28 days before the first dose of Tislelizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed. * Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy will be excluded from randomization; * Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded from randomization; Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE\>Grade 1.