sbrt in combination with sintilimab and gm-csf for the treatment of advanced nsclc

Conditions: NSCLC Stage IV

Summary: 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.


Eligibility criteria:
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 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.