Alflutinib Mesylate Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer （FLAG）

Exclusion Criteria

• •1. Treatment with any of the following:
• •3. The tissue type is mixed type, that is, patients with lung adenocarcinoma mixed with lung squamous cell carcinoma.
• •4. Patients with spinal cord compression, asymptomatic and stable brain metastases, except for those patients who have completion of the definitive therapy and steroids at least 28 days before investigation，or patients who received local radiotherapy for brain metastasis will be allowed in when the period of stabilization of brain metastases are at no shorter than 28 days.
• •5. Patients with other malignant tumors or have a history of other malignant tumors, except for basal cell carcinoma of the skin, carcinoma in situ of the cervix and ductal carcinoma in situ of the breast.
• •6. Any condition affecting the drug taking, or significantly affecting the absorption or the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit, chronic gastroenteropathy, disability in swallowing, history of gastrointestinal resection or surgery, uncured recurrent diarrhea, atrophic gastritis (the age of onset is less than 60 years old), stomach diseases, crohn's disease and ulcerative colitis that require long-term use of PPI antiacid drugs without cure.
• •7. Patients of organ insufficiency in bone marrow, liver and kidney meet the following requirements (patients should receive no blood transfusion, blood product, hematopoietic stimulating factors, and albumin two weeks before blood sampling of admission )：
• •* Absolute neutrophil count \< 1.5 x 109/L, Platelet count \< 75 x109/L, Haemoglobin \< 90 g/L;
• •* Alanine aminotransferase/Aspartate aminotransferase \> 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times in the presence of liver metastases;
• •* Total bilirubin \> 1.5 times ULN, or \>3 times ULN in the presence of definitive Gilbert's syndrome (Unbound hyperbilirubinemia) or liver metastases;
• •* Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation);
• •* The international standardized ratio (INR) was \> and 1.5, and the partial activation time of prothrombin (APTT) was \> 1.5 times ULN.
• •8. Any condition meets the following cardiac standard:
• •* Mean resting corrected QT interval (QTc)\>470 msec, obtained from 3 ECG, using the screening clinic ECG machine-derived QTc value.
• •* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250 msec
• •* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
• •* Echocardiographic examination: LVEF\<50%
• •9. Active infection with HBV, HCV, or HIV. All subjects will be screened for HBV, HCV, or Or HIV infection during the screening period:
• •* HBsAg positive, HBV DNA ≥1000cps/ml（or200IU/ml）
• •* Anti-HCV antibody was positive and HCV RNA was positive
• •* HIV antibody was positive
• •10. Interstitial lung disease, drug - induced interstitial pulmonary disease, history of radiation pneumonia which required steroid treatment; acute or progressive pulmonary symptoms may occur at baseline or interstitial pulmonary disease may be identified that the researchers considered not suitable for trail
• •11. Allergy to the study drug and/or its excipients is known or suspected
• •12. Women during pregnancy or lactation
• •13. Judgment by investigator that the patients should participate in the study if the patient is unlikely to comply with study procedure, restrictions, and requirements (for example, uncontrolled hypertension, uncontrolled diabetes, active bleeding constitution, etc.)