This study is an open-label, multicenter, phase II single arm trial to evaluate the efficacy and safety of SBRT in combination with sintilimab and GM-CSF for the treatment of patients with 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.