SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC

Inclusion Criteria: * Age at least 18 years. * ECOG PS 0-1. * Pathologically confirmed stage IV NSCLC. * Negative for driver genes including EGFR，ALK，and ROS-1. * Patients with disease progression after first-line platinum-based therapy without anti-PD-1 or PD-L1 treatment. * Patients with at least one lesion (size 1-5cm) eligible for SBRT (24Gy/3Fx) and simultaneously at least one measurable lesion (in addition to the lesion treated with SBRT) as defined by RECIST1.1. * Patients with brain metastasis are eligible if they are asymptomatic, neurologically stable, and off corticosteroids. * Life expectancy of more than 3 months. * Patients with no indications for palliative radiotherapy in the opinion of the investigator. * Patients with a prior history of surgery are eligible if they have recovered adequately from the toxicity and/or complications of surgery. * Signed informed consent for the use of fresh tumor biopsies before and during the treatment. * Women of childbearing age and men must agree to use effective contraception during the trial. * Adequate organ function within 1 week prior to the enrollment： 1. Adequate bone marrow function: hemoglobin ≥80g/L, white blood cell (WBC) count ≥ 4.0 \* 10 \^ 9/L or neutrophil count ≥ 1.5 \* 10 \^ 9/L, and platelet count ≥ 100 \* 10 \^ 9/L; 2. Adequate hepatic function: total bilirubin \< 1.5 x upper limit of normal (ULN). Note: If total bilirubin is \> 1.5 x ULN, direct bilirubin must ≤ ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN; 3. Adequate renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min; * Ability to understand and willingness to provide the informed consent. Exclusion Criteria: * Prior exposure to immunomodulatory agent,including but limited to anti-PD-1 or anti-PD-L1 antibodies. * Severe autoimmune disease: inflammatory bowel disease (including Crohn's disease and ulcerative colitis) 、rheumatoid arthritis、scleroderma、systemic lupus erythematosus 、Wegener's granulomatosis and related vasculitides. * Patients receiving non-platinum-based chemotherapy as first-line treatment * Mixed small cell with non-small cell lung cancer histology. * Pregnant or lactating women. * Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis. * History of any other malignancy. * Patients in whom palliative radiotherapy is indicated in the opinion of the investigator. * Active infection, congestive heart failure, myocardial infarction within the 6 months prior to enrollment, unstable angina pectoris or cardiac arrhythmia. * Prior allergic reaction or contraindications to sintilimab and GM-CSF. * Patients who have received tumor vaccine; or administration of live, attenuated vaccine within 4 weeks before the start of treatment. Note: Influenza vaccination is permitted only during influenza season, while live, attenuated influenza vaccine such as FluMist is not allowed. * Patients receiving concurrent chemotherapy drugs,other immunosuppressive agents,or other investigational treatment.Long-term corticosteroid users are also excluded. * Mental disorders, drug abuse, and social condition that may negatively impact compliance in the opinion of the investigator.