Study Evaluating Hemay022 In Subjects With HER2-Positive Advanced Breast Cancer

This is a phaseⅠsequential-group study of ascending single and multiple oral doses administered to subjects with HER2-Positive Advanced Breast Cancer. Each subject will receive a single dose of Hemay022, followed by a 1-week observation period, and then will receive Hemay022 administered once daily by mouth for 28 days. Each cycle consist of 28 days. Subjects will be enrolled in groups of 3 to 6. Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted. Part 2 is an extension part of three dose groups.

Inclusion criteria

• Male or female subjects aged 18 to 65 years;
• Histologically or cytologically confirmed and radiologically diagnosed advanced breast cancer subjects; and subjects who have failed standard therapy，or no effective therapy available for such subjects
• HER2 over-expression by IHC with score of 3+, or 2+ with FISH confirmation;
• Preferably measurable tumour lesion as defined by RECIST criteria1.1;
• Subjects have received chemotherapy at least 4 weeks prior to screening (at least 6 weeks of washout time frame if treated with mitomycin and nitrosoureas) and must have recovered from any toxic effects of the treatment --- to CTCAE 4.03≤ Grade 1;
• ECOG Performance Status of 0,1;
• Life expectancy of at least three months;
• Adequate bone marrow, liver, kidney function, meeting the following creteria:

ANC≥1.5×109/L, HB≥90g/L, PLT≥75×109/L； TBIL≤1.5×ULN, ALT≤1.5×ULN, AST≤1.5×ULN; Cr ≤1×ULN; BUN ≤1×ULN;

• Left ventricular ejection fraction (LVEF) ≧50% as measured by Ultrasonic cardiogram (UCG)
• All female and male subjects must agree and commit to the use of a reliable contraceptive regimen for the duration of the study and for at least 12 weeks after at the last dose of test article. Female subjects must have a negative serum or urine pregnancy test performed within 7 days prior to treatment;
• Ability to understand and the be willingness to sign a written informed consent before study entry;
• subjects would have good communication with the investigator and could comply with protocol

Exclusion criteria

• Patients with parenteral nutrition; malabsorption syndrome; or any condition possibly affecting drug absorption or inability to tolerate oral medications;
• Clinically QTc prolongation, ventricular tachycardia, ventricular fibrillation, heart block, myocardial infarction within 1 year, congestive heart failure, symptoms requiring medicine treatment patients with coronary heart disease;
• Ventricular ejection fraction (LVEF) <50％;
• Active infection (ie, requiring intravenous antibiotic or antiviral agent);
• Active central nervous system metastases
• Have received other clinical trials treatment within the 4 weeks prior to study;
• Have received other target therapy within the 4 weeks prior to study;
• Pregnant or breast feeding women;
• Have a known hypersensitivity to the test article or any of the excipient of the test article;
• Evidence of significant medical illness or abnormal laboratory finding that would make the subject inappropriate for this study by the investigator's judgment.
• Subjects cannot complete the study due to other reasons