Eribulin With or Without Trastuzumab-biosimilar in Patients With HER2-overexpressed Recurrent or Stage IV Breast Cancer

Inclusion Criteria:

• Adults ≥18 years old.

• Pathologically documented breast cancer that:

• is unresectable or metastatic

• has confirmed HER2 positive expression (immunohistochemistry or FISH) asdetermined according to American Society of Clinical Oncology - College ofAmerican Pathologists guidelines evaluated at a central laboratory

• was previously treated with trastuzumab, T-DM1, and taxane (whether inrecurrent/metastatic setting or neoadjuvant/adjuvant setting).

• Less than 4 prior lines of chemotherapy or HER2 targeted therapies fortreatment in metastatic disease (<4 treatment regimens for recurrent/metastaticdisease excluding adjuvant treatments)

• Documented radiologic progression (during or after most recent treatment or within 6months after completing adjuvant therapy).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1

• Male and female subjects of reproductive/childbearing potential must agree to use ahighly effective form of contraception or avoid intercourse during and uponcompletion of the study and for at least 4.5 months after the last dose of studytreatment.

• Adequate hematopoietic, renal and hepatic functions.

• Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3,platelet≥100,000/mm3, hemoglobin≥10g/mm3

• Adequate hepatic function: total bilirubin ≤1.5mg/dL, AST/ALT ≤2 x UNL, alkalinephosphatase ≤2.5 x UNL, in case with bone metastases alkaline phosphatase ≤5 x UNL

• Adequate renal function: Serum creatinine ≤1.5mg/dL

• a left ventricular ejection fraction of 50% or more (determined by echocardiographyor multiple-gated acquisition [MUGA(Multigated Blood Pool Scan)] scanning)

• CNS(central nervous system) metastasis is permitted if asymptomatic or controlledwith minimal steroid requirement and is documented to be non-progressing at studyentry.

• Negative urine pregnancy test within 7 days prior to registration in premenopausalpatients

• Ability to understand and comply with protocol during study period

• Patients should sign a written informed consent before study entry

Exclusion Criteria:

• Prior treatment with eribulin

• Uncontrolled or significant cardiovascular disease

• History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%)

• High-risk uncontrolled arrhythmias (ventricular tachycardia, high-gradeAtrioventricular-block, supraventricular arrhythmias, prolonged QTc(corrected QTinterval) which are not adequately rate-controlled)

• Angina pectoris requiring antianginal medication

• Clinically significant valvular heart disease

• Evidence of transmural infarction on ECG

• Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg)

• Pregnant or lactating women or women of childbearing potential, including womenwhose last menstrual period was ,12 months ago (unless surgically sterile) who areunable or unwilling to use adequate contraceptive measures during the studytreatment period.

• Patients who have history of cancer other than in situ uterine cervix cancer ornonmelanotic skin cancer and thyroid cancer. For other types of cancer, patientscould be included if there is no evidence of disease for more than 3 years.

• Patients with GI tract disease resulting in an inability to take oral medication,malabsorption syndrome, a requirement for IV alimentation, prior surgical proceduresaffecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerativecolitis)

• Subjects who have current active hepatic or biliary disease (with exception ofpatients with Gilbert's syndrome, asymptomatic gallstones, liver metastases orstable chronic liver disease per investigator assessment)

• Concurrent disease or serious medical disorder, for example, active or uncontrolledinfection, known interstitial lung disease (ILD) or any psychiatric conditionprohibiting understanding or rendering of informed consent.

• Patients who have a known immediate or delayed hypersensitivity reaction oridiosyncrasy to drugs chemically related to any of the study agents or theirexcipients.