Efficacy and Safety of Sintilimab With or Without Radiotherapy in Patients With Recurrent or IV NSCLC (EGFR -, ALK -) After Failure of Platinum-based Chemotherapy: A Randomized,Open Labled, Phase II Clinical Study

Inclusion Criteria:

1. Signed written informed consent prior to the implementation of any test-relatedprocess.

2. Age ≥ 18 and ≤ 75.

3. Life expectancy exceeding 3 months.

4. Non-small cell lung cancer is confirmed histologically or cytologically (either as aninitial diagnosis or a subsequent biopsy). However, the Sputum cytology results aloneare unacceptable. Cytology results of tracheal brush test, tracheal flush fluid andneedle aspiration puncture is acceptable.

5. The investigator confirms the presence of at least one measurable lesion according tothe RECIST 1.1 criteria.

6. Patients with stage IV, or recurrent NSCLC with histologically or cytologicallyconfirmed , according to the International Association for the Study of Lung Cancerand the Joint Committee on American Cancer Classification, 8th edition, TNM stage oflung cancer.

7. Patients confirmed by histological specimens not applicable to EGFR or ALK-targetedtherapy (with documented evidence of no tumor EGFR sensitivity mutations and no ALKgene rearrangements).

8. Eastern Oncology Collaborative Group (ECOG) fitness status score of 0 or 1.

9. Have received at least one regimen of platinum-containing chemotherapy with tumorprogression or inability to tolerate chemotherapy response in the most recentchemotherapy regimen.

10. Good hematopoiesis, defined as an absolute neutrophil count ≥1.5 × 109/L, plateletcount≥100 × 109/L, blood Erythropoietin ≥ 90 g/L

11. Good liver function, defined as total bilirubin levels ≤ 1.5 times the upper limit ofnormal(ULN); in patients without hepatic metastases, glutinous rice cereal is used asa supplement.

12. Aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN; forpatients with documented liver metastases, AST and ALT levels ≤ 5 times ULN.

13. Good renal function, defined as serum creatinine ≤ 1.5 times ULN or calculatedcreatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula); urine protein less than 2+on routine urinalysis, or 24-hour urine protein quantification < 1 g.

14. Good coagulation, defined as an International Standardised Ratio (INR) or ProthrombinTime (PT) ≤ 1.5 times ULN; if the subject is receiving anticoagulant therapy, providedthat the PT is within the intended use range of the anticoagulant.

15. For female subjects of childbearing age, a negative urine or serum pregnancy testshould be presented within 3 days prior to receiving the first study drugadministration (Week 1, Day 1). If the urine pregnancy test result cannot be confirmedas negative, a blood pregnancy test will be requested.

16. If there is a risk of conception, both male and female patients need to use highlyeffective contraception (i.e., a method with a failure rate of less than 1% per year)and continue until at least 180 days after discontinuation of the trial treatment.

Exclusion Criteria:

1. Currently participating in an interventional clinical research treatment, or hasreceived another investigational drug or used an investigational device within 4 weeksprior to the first administration of the drug.

2. Previously received an anti-PD-1, anti-PD-L1, or anti-PD-L2 drug or a drug thatstimulates or synergistically inhibits another T-cell receptor (e.g., CTLA-4, OX-40,CD137).

3. Systemic systemic therapy with an anti-lung cancer indication with a proprietaryChinese medicine or immunomodulatory drug (including thymidine, interferon,interleukin, except for local use for pleural control) within 2 weeks prior to thefirst dose, or major surgery within 3 weeks prior to the first dose.

4. Previous experience of chest radiotherapy.

5. Palliative radiotherapy completed within 7 days prior to the first administration ofthe drug.

6. Presence of clinically active diverticulitis, abdominal abscesses, gastrointestinalobstruction.

7. Have received a transplant of a solid organ or blood system.

8. Presence of clinically uncontrollable pleural effusion/abdominal fluid.

9. Known severe allergic reaction (grade ≥3) to cedirizumab, or other immunotherapeuticagents.

10. Active autoimmune disease requiring systemic therapy (e.g., use of disease-modifyingdrugs, corticosteroids, or immunosuppressants) occurring within 2 years prior to thefirst dose of the drug. Alternative therapies (e.g., thyroxine, insulin, orphysiologic corticosteroids for adrenal or pituitary insufficiency) are not consideredsystemic therapy.

11. Diagnosis of immunodeficiency or being on systemic glucocorticoid therapy or any otherform of immunosuppressive therapy within 7 days prior to the first administration ofthe study; physiological doses of glucocorticoids (≤10 mg/day of prednisone orequivalent) are permitted.

12. Have not sufficiently recovered from toxicity and/or complications from any of theinterventions prior to initiating treatment (i.e. ≤ grade 1 or at baseline, notincluding weakness or hair loss).

13. Diagnosis of other malignancies within 5 years prior to the first dose, withexceptions including radically treated basal cell carcinoma of the skin, squamous cellcarcinoma of the skin, and/or radically resected carcinoma in situ.

14. Symptomatic central nerve metastases. Patients with asymptomatic brain metastases orstable symptoms after treatment of brain metastatic lesions may be enrolled in thisstudy if all of the following criteria are met: measurable lesions outside the centralnervous system; absence of midbrain, bridge, cerebellum, medulla oblongata or spinalcord metastases; maintenance of clinical stability for at least 2 weeks; and cessationof hormonal therapy 3 days prior to the first dose of study drug.

15. A history of non-infectious pneumonia requiring glucocorticoid therapy or currentinterstitial lung disease within 1 year prior to the first administration of the drug.

16. Active infections that require systemic treatment.

17. (a) The known existence of a mental illness or substance abuse condition that mayaffect compliance with the test requirements.

18. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibodypositive).

19. Note: Subjects with hepatitis B who meet the following criteria are also eligible forenrollment: HBV viral load must be <1000 copies/ml (200 IU/ml) prior to first dose andsubjects should receive anti-HBV therapy to avoid viral reactivation throughout theduration of study chemotherapy drug therapy. Subjects with anti-HBc (+), HBsAg (-),anti-HB (-) and HBV viral load (-) do not need to receive prophylactic anti-HBVtherapy but need to be monitored closely for viral reactivation.

20. Active HCV-infected subjects (HCV antibody-positive and HCV-RNA levels above the lowerlimit of detection).

21. Live vaccine within 30 days prior to first dose (Cycle 1, Day 1); NOTE: Injectableinactivated viral vaccine against seasonal influenza is allowed up to 30 days prior tofirst dose; however, live attenuated influenza vaccine for intranasal administrationis not allowed.

22. Evidence of a medical history or illness that could interfere with the results of thetrial, prevent the subject from participating throughout the study, abnormal valuesfor treatment or laboratory tests, or other circumstances that, in the opinion of theinvestigator, make enrollment unsuitable.

23. Breastfeeding women.