TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which
prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell
activity, thus enhancing immune response and has potential to treat various types of tumors.
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 but
failed 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 cells
performed 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 products
within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT)
2. Blood biochemical examination: alanine transaminase (ALT) and aspartate
aminotransferase (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，or
calculated creatinine clearance (CrCl) ≥50ml/min； calculated creatinine clearance
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) ,international
normalized ratio (INR) ,prothrombin time (PT) ≤1.5×ULN；
4. left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥
6. Male or female subjects should agree to use an adequate method of contraception
starting with the first dose of study therapy through 6 months after the last dose of
study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or
breastfeeding women, and a negative pregnancy test are received within 7 days before
7. Understood and signed an informed consent form.
1. Prior therapy with Anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other
immunotherapy 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 randomization
with the exception of cured basal cell carcinoma of skin and carcinoma in situ of
4. Has any active autoimmune disease or history of autoimmune disease, such as autoimmune
hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, asthma patients
who need bronchiectasis for medical intervention; Subjects with the vitiligo without
systemic 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 absorbable
local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is
required 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 requiring
recurrent drainage procedures.
8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with
blood vessels is unclear.
9. Has any bleeding or bleeding events ≥ grade 3 or with unhealed wounds, ulcerative , or
fractures within 4 weeks prior to the first administration.
10. Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous
meningitis within 8 weeks before the first-dosing, or brain or leptomeningeal disease
found by CT or MRI during screening.
11. Has received chemotherapy, surgery, radiotherapy, the last treatment from the first
dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral
fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for
less than 6 weeks. Patients whose adverse events (except alopecia) caused by previous
treatment did not recover to ≤ grade 1.
12. Patients with any serious and/or uncontrollable disease, including :
1. Has poor blood pressure control, systolic blood pressure ≥ 150 mmHg, diastolic
blood pressure ≥ 90 mmHg;
2. Thrombotic events, ischemic attacks, myocardial infarction, grade 2 congestive
heart failure or arrhythmias requiring treatment including QTc ≥ 480ms occurred
within 6 months of first administration;
3. Severe active or uncontrolled infections ≥ grade 2;
4. Has known clinical history of liver diseases, including viral hepatitis, known
carriers 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 virus
infection (HCV) and HCV RNA positive > 1 *103 copies/mL, or other decompensated
hepatitis and chronic hepatitis, which require antiviral treatment;
5. HIV positive;
6. Poor control of diabetes mellitus, fasting blood-glucose ≥ grade 2;
13. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first
14. According to the judgement of the researchers, there are other factors that may lead
to the termination of the study.