A Clinica Study of Pyrotinib in Patients of Advanced Non-Small Cell Lung Cancer With HER2 Mutation

Inclusion criteria

• ECOG performance status of 0 to 1.
• Life expectancy of more than 3 months.
• At least one measurable lesion exists.(RECIST 1.1).
• Histologically or cytologic confirmed Non-small cell lung cancer, Phase IIIB or IV according to IASLC 2009.
• Failed prior therapies.(RECIST 1.1).
• Confirmed HER2 mutation by Central Laboratory。
• More than one prior Platinum based chemotherapy for advanced and/or metastatic, or recurrent NSCLC in neoadjuvant or adjuvant chemotherapy.
• Required laboratory values including following parameters:

ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 90 g/L; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤2 x ULN or ALT and AST: ≤5x ULN for patients with liver metastasis; BUN and Cr: ≤1.5 x ULN； creatine clearance rate: ≥ 50 mL/min; LVEF: ≥ 50%; QTcF: < 470 ms for female and < 450 ms for male.

• Signed informed consent

Exclusion criteria

• Previous therapy with other HER2 inhibitors.
• History of severe hypersensitivity reactions to the excipients of the trial drugs.
• Have clinically significant cavity effusion,such as pleural effusion、 pericardial effusion or ascites and require clinical intervention
• Active brain metastases
• Other malignancy within the past (including primary brain tumor or Leptomeningeal tumor), other than basal cell skin cancer or carcinoma in situ of the cervix
• Persistence of clinically relevant therapy related toxicities from previous therapy (greater than Common Terminology Criteria for Adverse Event(CTCAE) 4.0 grade 1)
• Treatment with surgery, chemotherapy, radiotherapy or other target therapy within the past 4 weeks before start of therapy
• Uncontrolled hypertensin,diabetes.
• unstable angina, history of myocardial infarction in the past 6 months, congestive heart failure>NYHA II, serious cardiac arrhythmia
• Active infection
• Variety of factors that affect the oral medication (such as unable to swallow, chronic diarrhea, bowel obstruction and other gastrointestinal disorders or abnormalities
• History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
• Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial.
• Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
• Known history of neurological or psychiatric disease, including epilepsy or dementia.
• Treatment in another clinical trial within the past 4 weeks before start of therapy
• Any of the other conditions of which researchers believe that the patient is not fit to take part in the study.