Study of TQB2450 Combined With Anlotinib in Patients With Advanced Non-small Cell Lung Cancer（NSCLC）

Inclusion Criteria:

1.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.

2. Histologically or cytologically confirmed Epidermal Growth Factor Receptor (EGFR)/Anaplastic Lymphoma Kinase (ALK) wild type non-small cell lung cancer.

3. Advanced patients who had received at least first-line of standard chemotherapy butfailed or intolerable , with at least one measurable lesion based on RECIST 1.1.

4. PD-L1-positive tumor status (TPS≥1%) as determined by an immunohistochemistry (IHC)assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cellsperformed by a central laboratory.

5.The main organs function are normally, the following criteria are met:

1. routine blood tests：hemoglobin (Hb)≥90g/L (no blood transfusion and blood productswithin 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT) ≥80×109/L;

2. Blood biochemical examination: alanine transaminase (ALT) and aspartateaminotransferase (AST)≤ 2.5×ULN (when the liver is invaded，≤ 5×ULN);total bilirubin (TBIL)≤1.5×ULN (Gilbert syndrome patients，≤ 3×ULN)；serum creatinine (Cr) ≤1.5×ULN，orcalculated creatinine clearance (CrCl) ≥50ml/min； calculated creatinine clearanceformula：Ccr=(140-age)×weight(kg)/72×Scr(mg/dl)Ccr=[(140-age)×weight(kg)]/[0.818×Scr(umol/L) (According to the calculation results ,female Patients ×0.85；1 mg/dL = 88.41 umol/ L)

3. Coagulation function: activated partial thromboplastin time (aPTT) ,internationalnormalized ratio (INR) ,prothrombin time (PT) ≤1.5×ULN；

4. left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥ 50%.

5. Male or female subjects should agree to use an adequate method of contraceptionstarting with the first dose of study therapy through 6 months after the last dose ofstudy (such as intrauterine devices , contraceptives or condoms) ；No pregnant orbreastfeeding women, and a negative pregnancy test are received within 7 days beforethe randomization.

6. Understood and signed an informed consent form.

Exclusion Criteria:

1. Prior therapy with Anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or otherimmunotherapy against PD-1/PD-L1.

2. Severe hypersensitivity occurs after administration of other monoclonal antibodies.

3. Diagnosed and/or treated additional malignancy within 5 years prior to randomizationwith the exception of cured basal cell carcinoma of skin and carcinoma in situ ofcervix.

4. Has any active autoimmune disease or history of autoimmune disease, such as autoimmunehepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, asthma patientswho need bronchiectasis for medical intervention; Subjects with the vitiligo withoutsystemic treatment, psoriasis, alopecia, well-controlled type I diabetes mellitus,hypothyroidism stable on hormone replacement will not be excluded from this study.

5. Immunosuppressive therapy with immunosuppressive agents or systemic or absorbablelocal hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) isrequired for the purpose of immunosuppression.

6. Has multiple factors affecting oral medication, such as inability to swallow,post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.

7. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiringrecurrent drainage procedures.

8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary withblood vessels is unclear.

9. Has any bleeding or bleeding events ≥ grade 3 or with unhealed wounds, ulcerative , orfractures within 4 weeks prior to the first administration.

10. Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerousmeningitis within 8 weeks before the first-dosing, or brain or leptomeningeal diseasefound by CT or MRI during screening.

11. Has received chemotherapy, surgery, radiotherapy, the last treatment from the firstdose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oralfluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea forless than 6 weeks. Patients whose adverse events (except alopecia) caused by previoustreatment did not recover to ≤ grade 1.

12. Patients with any serious and/or uncontrollable disease, including :

13. Has poor blood pressure control, systolic blood pressure ≥ 150 mmHg, diastolicblood pressure ≥ 90 mmHg;

14. Thrombotic events, ischemic attacks, myocardial infarction, grade 2 congestiveheart failure or arrhythmias requiring treatment including QTc ≥ 480ms occurredwithin 6 months of first administration;

15. Severe active or uncontrolled infections ≥ grade 2;

16. Has known clinical history of liver diseases, including viral hepatitis, knowncarriers of hepatitis B virus (HBV) must exclude active HBV infection, that is,HBV DNA positive > 1 *104 copies/mL or > 2000 IU/mL, known hepatitis C virusinfection (HCV) and HCV RNA positive > 1 *103 copies/mL, or other decompensatedhepatitis and chronic hepatitis, which require antiviral treatment;

17. HIV positive;

18. Poor control of diabetes mellitus, fasting blood-glucose ≥ grade 2;

19. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to firstadministration.

20. According to the judgement of the researchers, there are other factors that may leadto the termination of the study.