A Study of Mitoxantrone Hydrochloride Liposome Injection in Patients With Advanced HER2 Negative Breast Cancer

Inclusion Criteria:

1. Voluntarily participate in this study and sign informed consent form;
2. Male or female patients aged 18 to 75 years (inclusive);
3. Histologically confirmed diagnosis of HER-2 negative breast cancer (Includingimmunohistochemistry HER2 0 or 1+, immunohistochemistry HER2 2+ must be confirmed asnegative by in situ hybridization);
4. Patients with unresectable locally advanced or recurrent breast cancer with diseaseprogression after first-line or higher chemotherapy；
5. Hormone receptor (HR) negative breast cancer or HR-positive breast cancer that is notsuitable for endocrine treatment or is resistant to endocrine treatment.
6. Prior treatment with both an anthracycline (i.e., doxorubicin or epirubicin) and ataxane (i.e., paclitaxel or docetaxel) at least (acceptable for patients notpreviously treated with anthracyclines due to high risk factors for cardiotoxicity),and four prior chemotherapy regimens at most；
7. At least one measurable lesion according to RECIST v1.1;
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
9. Patients must meet the following criteria prior to treatment (not receiving bloodtransfusion or growth factors therapy within 14 days before the first administration):

• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
• Hemoglobin ≥ 90g / L;
• Platelet count ≥ 90 × 109/L;
• Creatinine ≤1.5 × upper limit of normal (ULN);
• Total bilirubin ≤ 1.5×ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ×ULN (≤ 5 ×ULN for liver metastasis);

10. For women of childbearing potential: the serum pregnancy test must be negative, andpatients are willing to take adequate contraceptive measures during the treatmentperiod and for at least 6 months after the last dose of the study drug;
11. Good compliance and willingness to cooperate with follow-up visits.

Exclusion Criteria:

1. Patients who have severe allergic reactions to mitoxantrone hydrochloride or liposomepreparation ingredients;
2. History of other malignancy within 3 years, except for radical cure of carcinoma insitu of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin;
3. Brain metastases and meningeal metastasis;
4. Patients with active hepatitis B (HBsAg positive with hepatitis B virus DNA ≥ 2000IU/mL), active hepatitis C (hepatitis C virus antibody positive with hepatitis C virusRNA above the lower limit of detection of the study center), or human immunodeficiencyvirus (HIV) antibody positive;
5. Life expectancy < 3 months;
6. Previous treatment with the anthracyclines, with the total cumulative dose (doxorubicin equivalent) >350 mg/m2;
7. Adverse events from the previous treatment have not resolved to ≤ Grade 1 based onCTCAE (except for the toxicity without safety risk judged by the investigator, such asalopecia, hyperpigmentation);
8. Impaired cardiac function or serious cardiac disease:

• Long corrected QT interval syndrome or corrected QT interval > 480 ms;
• Complete left bundle branch block, II-III degree atrioventricular block;
• Severe, uncontrolled arrhythmias requiring pharmacological treatment;
• History of chronic congestive heart failure, New York Heart Association ≥ grade 3;
• Cardiac ejection fraction < 50% within 6 months prior to screening;
• Heart valve disease with CTCAE ≥ grade 3;
• ECG evidence of myocardial infarction, unstable angina, severe ventriculararrhythmias, history of severe pericardial disease, and acute ischemic or activeconduction system abnormalities within 6 months prior to screening;

9. Uncontrollable hypertension (defined as a measured systolic blood pressure ≥ 160 mmHgor diastolic blood pressure ≥ 100 mmHg under pharmacological control);
10. Active bacterial, fungal or viral infections that require intravenous infusiontreatment within 1 week prior to the first dose;
11. Any anticancer treatment (including chemotherapy, radiotherapy, molecular targetedtherapy, immunotherapy, endocrine therapy) within 4 weeks prior to the first dose,immunomodulators as adjuvant therapy for malignancy within 2 weeks prior to the firstdose, any anti-tumor proprietary Chinese medicine (except for those in the category ofsupporting and relieving symptoms) within 2 weeks prior to the first dose;
12. Patients who enrolled in any other clinical trials within 4 weeks prior to the firstdose;
13. Patients who undergone major surgery within 12 weeks before the first dose, or have asurgical schedule during the study period;
14. Patients with thrombosis or thromboembolism within 6 months prior to screening;
15. Lactating female;
16. Serious and/or uncontrolled medical condition that, in the judgment of theinvestigator, may affect the patient's participation in this study (including, but notlimited to: diabetes not effectively controlled, kidney disease requiring dialysis,severe liver disease, life-threatening autoimmune and bleeding disorders, substanceabuse, neurological disorders, etc.);
17. Not suitable for this study as decided by the investigator due to other reasons.