SinTilimab After Radiation (STAR Study)

Inclusion Criteria:

1. Signed written informed consent;

2. Age ≥ 18 years ;

3. Histologically or cytologically confirmed NSCLC, without EGFR sensitive mutation (must) or no known ALK/ROS1 positive;

4. Stage IIIB-IV (AJCC 8th edition) or recurrent/progressive disease aftermultidisciplinary treatment for local advanced disease or chemotherapy intolerantpatients;

5. Patients must have disease progression or recurrence after receiving first/secondline systemic therapy for advanced or metastasis disease, or patients withchemotherapy intolerance during chemotherapy: 1) Maintenance therapy after platinumbased chemo-doublet shall not be considered as a separated treatment regimen, 2)Patients with locally advanced disease treated with platinum-based adjuvant,neoadjuvant therapy or radical chemoradiotherapy, and tumor recurrence ( local ormetastatic ) within 6 months after completion of treatment are suitable forinclusion; 3) Subjects who relapsed more than 6 months after receivingplatinum-based adjuvant, neoadjuvant therapy or radical chemoradiotherapy forlocally advanced disease, and then progressed during or after receiving systemictreatment for recurrent tumors were suitable for inclusion; 4) Patients who receivedplatinum-based double-drug chemotherapy after progression or chemotherapyintolerance were considered as second-line patients after first-line treatment; 5)After the progression of platinum-containing double-drug chemotherapy, patients whoprogressed again with a single-drug chemotherapy regimen or chemotherapy intolerancewere considered as third-line patients after second-line treatment.

6. ECOG PS 0-1, with expected survival over 3 months;

7. Patients shall have at least one leision eligible for radiation, e.g. bonemetastasis, intrapulmonary node, adrenal disease, etc. Patient must have at leastone disease (other than radiation target) according to RECIST 1.1: 1) Patient musthave received radiation for 1 location after disease progression or recurrence afterfirst line treatment for advanced or metastasis disease, the biological dose of asingle site of radiotherapy is required to exceed 30 Gy ( 6 Gy × 5, or other ) orthe plan can reach 30 Gy. 2) Radiotherapy can be performed on the same day asSindilizumab, but the last radiotherapy is no more than 3 weeks after the start ofSindilizumab treatment.

8. Adequate marrow and organ function as per baseline CBC/CMP/Urine test;

9. Prior systemic anti-tumor therapy should be completed at least 4 weeks beforeenrollment, and adverse events of prior treatment shall be return to ≤G1 per CTCAE (except for alopecic or any non-clinical significant laboratory abnormalities) ;

10. Women with childbearing potential or men whose female partners are with childbearingpotential must agree to use efficient contraceptive methods during the studytreatment period until 90 days after last dose of study treatment.

Exclusion Criteria:

1. Previously treated by any immune therapy;

2. Active infection including HBV, HCV, and HIV;

3. Serious marrow or organ malfunction, e.g. hepatic or renal dysfunction;

4. Patients with unstable CNS metastasis or require corticosteroids to control CNSsymptoms. Patients with stable brain metastasis after radiation (3 weeks) will beeligible;

5. Active or autoimmune disease;

6. ILD, including drug-induced ILD, radiation pneumonia that required corticosteroids,or any clinical implication for active ILD;

7. Any course that lead to treatment with continuous systemic corticosteroids >10mg/day prednisone or equivalent dose of other steroids;

8. Pregnant or lactating women.