Anlotinib Plus Chemotherapy for Patients With Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

1. Age：18~75 years;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2
3. Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC who have previously received one lines chemotherapy, EGFR TKI or ALK inhibitor (whom with EGFR or ALK mutation but not with T790 M positive) treatment before participating；
4. Subjects with at least one measurable lesion as defined by RECIST (version 1.1),which is confirmed by computed tomography (CT) scan or MRI .
5. Subjects without brain metastases or asymptomatic brain metastases, and not needing for dehydrating agents or corticosteroids to control intracranial symptoms;
6. Survival expectation ≥ 3 months;
7. The main organ function is normal;
8. Females of childbearing potential must be a pregnancy test in 7 days before participating ( including serum or urine), and the results were negative.
9. Subjects provided written informed consent before participating, willing and able to comply with all aspects of the protocol

Exclusion Criteria:

1. Small Cell Lung Cancer; 2. Subjects with symptomatic brain metastases; 3. Survival expectation < 3 months; 4. examined as positive in EGFR&ALK mutation detection and never take the treatment of TKIs 5. Blood transfusion is required in the first dose of drug treatment within 14 days ; 6. The interval of subjects had received chemotherapy, biotherapy, radiotherapy or other anticancer therapies in the first dose of drug treatment within 21 days(excluding palliative radiotherapy); 7. The risk of active bleeding; 8. Subjects with uncontrolled blood pressure with medication (140/90 mmHg) 9. Laboratory values and organ functions ： （1）Hematologic insufficiency:

1. Hemoglobin (Hb)<8.5 g/dL，
2. Absolute neutrophil count (ANC)≤1.5×109/L，
3. Platelet count (PLT)< 100×109/L； （2）Insufficient liver function:
4. Bilirubin > 1.5×the upper limit of normal (ULN)
5. Alanine aminotransferase (ALT), or Aspartate aminotransferase (AST) >3.0×(ULN), When liver metastases,Bilirubin > 1.5×ULN, ALT or AST >5.0×(ULN.
6. serum creatinine ≤1.0×（ULN）, or creatinine clearance > 50 mL/min( calculated per the Cockcroft and Gault formula) (3) Subjects with positive for HBV surface antigen ( HBsAg)or anti-hcv (4)Subjects with Interstitial lung disease (5)Insufficient renal function: serum creatinine≥ 1.5×（ULN）, or creatinine clearance <60 mL/min

10. impairment of heart function: (1)Left ventricular ejection fraction (LVEF) <45% (LVEF evaluation is not required for subjects have no history of congestive heart failure), (2)Unstable angina, (3)Severe arrhythmia, (4)NYHA III or IVgrade of congestive heart failure, (5) Subjects with myocardial infarction within the last 12 months before entering the trial, (6)Pericardial effusion, 11. Subjects with liver fibrosis or hepatic cirrhosis 12. (1)Subjects with other active malignancy (except for definitively treated non melanoma skin cancer,carcinoma in-situ of the cervix,or other cancers that are treated with curative treatment and have no signs of recurrence for at least 5 years ) , (2)Subjects with dysphagia,malabsorption,chronic gastrointestinal diseases,or other medical history may hinder compliance and / or experimental drug absorption, 13. Subjects with major surgery in the first dose of drug treatment within 28 days, 14. Subjects with positive unknown human immunodeficiency virus.