Clinical Study of Recombinant Anti-HER2 Humanized Monoclonal Antibody for Injection

For single dose:

Inclusion Criteria:

1. Aged 18 to 65 years;

2. Histopathologically confirmed breast cancer;

3. HER-2 positive (definition: the immunohistochemistry (IHC) test of pathological
samples showed HER-2 +++ or immunohistochemistry (IHC) test showed HER-2 ++ and
positive FISH amplification test);

4. HER2-positive breast cancer patients who have no lesion after surgery and never
received anti-HER-2 treatment;

5. The investigators consider that the subject has recovered from the toxic reactions
caused by the previous chemotherapy 4 weeks after the last chemotherapy.

6. The expected survival is 3 months or longer;

7. ECOG performance status is 0, 1 or 2;

8. The left ventricular ejection fraction (LVEF)≥50%;

9. The major organ function is normal and laboratory tests meet relevant criteria:

l Hematology test:

- Hb≥90 g/L (no blood transfusion within 14 days);

- ANC≥1.5×109 /L;

- PLT≥100×109 /L; l Hepatic and renal function tests:

- TBIL≤1.5×ULN (upper limit of normal);

- ALT and AST≤2.5×ULN;

- Serum Cr ≤ULN;

10. Normal coagulation function test;

11. Voluntarily sign the written informed consent form

Exclusion Criteria:

1. Pregnant or breastfeeding females; or women of childbearing potential who have
positive urine pregnancy test; or any subjects who are able to bear or father a child
but cannot or are unwilling to adopt medically acceptable effective contraceptive
methods during the study period and within 3 months after the end of the study;

2. Subjects who have any of the following cardiac conditions:

- Unstable angina pectoris;

- Medical history of congestive heart failure;

- Previous medical history of myocardial infarction, coronary artery bypass
grafting or coronary stent implantation;

- Clinically significant pericardial diseases and valvular heart diseases;

- Serious uncontrolled arrhythmia;

- Any other cardiac diseases which may cause safety risks for patients if they are
enrolled in this study;

3. Uncontrolled hypertension (defined as screening systolic blood pressure ≥ 180mmHg
and/or diastolic blood pressure ≥110mmHg);

4. Known HIV, HBV or HCV infection;

5. Allergic constitution; known allergic to the components of the investigational
product;

6. Have drug abuse history or alcohol addiction history;

7. Participated in other clinical studies within 4 weeks before the initiation of the
study;

8. Have complicated diseases which may interfere with study participation or evaluation
at the discretion of the investigator, e.g., uncontrolled infection, coagulation
disorders and other diseases, or the investigators consider that participation in this
study may lead to greater risks for patients.

For multiple dose groups:

Inclusion Criteria:

1. Aged 18 to 65 years;

2. Histopathologically confirmed breast cancer;

3. HER-2 positive (definition: the immunohistochemistry (IHC) test of pathological
samples showed HER-2 +++ or immunohistochemistry (IHC) test showed HER-2 ++ and
positive FISH amplification test);

4. Patients with metastatic breast cancer who failed to respond to previous chemotherapy
and no more than three lines, and never received anti-HER-2 treatment(subjects in
single dose group who experienced disease progression but meet other
inclusion/exclusion criteria can be enrolled);

5. There is at least one measurable target lesion (based on RECIST 1.1 criteria):

- According to Response Evaluation Criteria in Solid Tumors (RECIST V1.1), the
target lesions must be accurately measured in at least one dimension (refer to
appendix 5);

- No radiotherapy for target lesions;

6. The investigators consider that the subject has recovered from the toxic reactions
caused by the previous chemotherapy 4 weeks after the last chemotherapy (subjects who
are receiving Xeloda monotherapy and achieve efficacy or stable disease can be
enrolled in this study).

7. The expected survival is 3 months or longer;

8. ECOG performance status is 0, 1 or 2;

9. The left ventricular ejection fraction (LVEF)≥50%;

10. The major organ function is normal and laboratory tests meet relevant criteria:

l Hematology test:

- Hb≥90 g/L (no blood transfusion within 14 days);

- ANC≥1.5×109 /L;

- PLT≥100×109 /L; l Hepatic and renal function tests:

- TBIL≤1.5×ULN (upper limit of normal);

- ALT and AST≤2.5×ULN; if there is any hepatic metastasis, ALT and AST ≤5×ULN;

- Serum Cr ≤ULN;

11. Normal coagulation function test;

12. Voluntarily sign the written informed consent form.

Exclusion Criteria:

1. Pregnant or breastfeeding females; or women of childbearing potential who have
positive urine pregnancy test; or any subjects who are able to bear or father a child
but cannot or are unwilling to adopt medically acceptable effective contraceptive
methods during the study period and within 3 months after the end of the study;

2. Subjects with known or suspected brain metastasis: Subjects with evidence indicating
signs or symptoms of brain metastasis are not allowed to participate in this study
unless such brain metastasis is excluded by CT or MRI. However, subjects whose brain
metastasis lesions have been controlled can be enrolled (no progression within at
least 4 weeks after radiotherapy and/or no neurological symptom or sign after surgical
resection, treatment with dexamethasone or mannitol is not necessary);

3. Subjects who had disease progression after previous chemotherapy with Xeloda.

4. Subjects who have any of the following cardiac conditions:

- Unstable angina pectoris;

- Medical history of congestive heart failure;

- Previous medical history of myocardial infarction, coronary artery bypass
grafting or coronary stent implantation;

- Clinically significant pericardial diseases and valvular heart diseases;

- Serious uncontrolled arrhythmia;

- Any other cardiac diseases which may cause safety risks for patients if they are
enrolled in this study;

5. Uncontrolled hypertension (defined as screening systolic blood pressure ≥ 180mmHg
and/or diastolic blood pressure ≥110mmHg);

6. Known HIV, HBV or HCV infection;

7. Allergic constitution; known allergic to the components of the investigational
product;

8. Have drug abuse history or alcohol addiction history;

9. Participated in other clinical studies within 4 weeks before the initiation of the
study;

10. Have complicated diseases which may interfere with study participation or evaluation
at the discretion of the investigator, e.g., uncontrolled infection, coagulation
disorders and other diseases, or the investigators consider that participation in this
study may lead to greater risks for patients.