This prospective, single-center, randomized, controlled study will evaluate the efficacy and safety of sintilimab or placebo in combination with chemotherapy as second-line treatment for patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Treatment may continue as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Inclusion Criteria:

1. Volunteer to participate in clinical research; fully understand and know the research and sign informed consent;
2. Age ≥ 18 years old and ≤ 75 years old, either sex;
3. Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;
4. Has a histologically or cytologically confirmed diagnosis of stage IV (according to the 8th edition of the International Association for the Study of Lung Cancer) nonsquamous NSCLC;
5. Have at least one measurable lesion as defined by RECIST 1.1;
6. Has progression of disease after treatment with at least two cycles of a platinum-containing doublet chemotherapy according to RECIST V.1.1;
7. Patients without activating EGFR mutation;
8. Normal hepatic function: total bilirubin≤1.5×normal upper limit (ULN); Alanine aminotransferase and Aspartate aminotransferase levels ≤2.5×ULN or ≤5×ULN if liver metastasis is present;
9. Normal renal function: Creatinine ≤1.5×ULN or calculated creatinine clearance ≥45 mL/min (using Cockcroft/Gault formula to calculate );
10. Normal hematological function: absolute neutrophil count ≥1.5×109/L, platelet count ≥70×109/L, hemoglobin≥80g/L [no blood transfusion or erythropoietin (EPO) within 7 days] Dependency];
11. Has a life expectancy of at ≥3 months.

Exclusion Criteria:

1. ECOG PS >2;
2. Small cell lung cancer and squamous NSCLC;
3. EGFR mutation or mutation status unknown;
4. Known hypersensitivity or allergy to monoclonal antibody;
5. Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways);
6. Active autoimmune disease, or a documented history of autoimmune disease;
7. Treatment with systemic corticosteroids (prednisone≥10mg per day or equivalent dose) or other systemic immunosuppressive medications within 2 weeks prior to the first dose;
8. Known history or active human immunodeficiency virus (HIV);
9. Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection;
10. Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment;
11. Active or poorly controlled severe infection;
12. Have serious cardiovascular disease: Symptomatic congestive heart failure (New York Heart Association grade III-IV), unstable angina pectoris, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 3 months before randomization;
13. Received thoracic radiation therapy of >30 Gy within 6 months prior to first dose of study drug;
14. Completed palliative radiotherapy within 7 days prior to first dose of study drug;
15. Pregnant or lactating women.