| Eligibility |
Inclusion Criteria:
1. Written informed consent obtained prior to performing any protocol-related procedures
2. Male or female, age = 18 years old at the time of screening.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Subject has histologically confirmed HER2 positive metastatic breast cancer. Note: the
definition of HER2 positive is to have at least once 3+ by IHC, FISH positive and CISH
positive in the pathological test/retesting conducted at least once by investigational
site or qualified central lab which met national standard.
5. Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic
setting (mandatory to have trastuzumab, and other anti-HER2 agents e.g. lapatinib,
pyrotinib, pertuzumab, or T-DM1), regardless of having received (neo)adjuvant
anti-HER2 therapy or not
6. Have received treatment with no more than three lines of therapy overall in the
metastatic setting (including anti-HER2 targeted therapy or chemotherapy) and must
have disease progressed on or after, the most recent line of therapy. per RECIST 1.1.
- Prior radiotherapy, chemotherapy, hormonal therapies are allowed
- Endocrine therapies will not be considered as previous lines of therapy in the
metastatic setting.
- Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months
of the completion of therapy will be considered a line of treatment for
metastatic disease.
- Dose interruptions, delays, pauses during previous therapy, or changes in therapy
to manage toxicity will not constitute a new line of therapy provided disease
progression did not occur
7. Subject has at least one measurable lesion per RECIST 1.1.
8. Previous adverse events associated with anti-tumor therapy have been recovered to
NCI-CTCAE v4.03 Grade =1 (except NCI-CTCAE v4.03 Grade =2 alopecia, stable sensory
neuropathy, or stabilized electrolyte disturbance after fluid transfusion).
9. Subject has life expectancy =12 weeks.
10. Subject has no supportive therapy of blood transfusion or growth factor within 4 weeks
before randomization and has adequate organ functions as defined below:
- Absolute Neutrophil count (= 1.5 *109/L)
- Platelets count (= 100 *109/L)
- Hemoglobin (= 90 g/L)
- Serum creatinine (=1.5 times the upper limit of normal (ULN)) or calculated
creatinine clearance (=50 mL/min) (per Cockcroft-Gault formula; see Appendix 4)
- Total bilirubin = 1.5 times the upper limit of normal (ULN) or direct bilirubin =
1.0 times the upper limit of normal (ULN)AST and ALT =2 times the upper limit of
normal (ULN), and liver metastasis must be =5 times the upper limit of normal
(ULN).
- Cardiac color Doppler LVEF = 50%
11. Subject has a negative test result of pregnancy test at randomization. Women with
childbearing potential are promised to take adequate and effective contraceptive
measures or abstinence within six months from the start of the study to the end of the
study and after the last medication are admitted. Or the women in the study were women
with no potential fertility, defined as:
- Women underwent surgical sterilization (hysterectomy, bilateral ovariectomy or
bilateral salpingectomy), or
- Women = 60 years of age, or
- Women are in the ages = 40 years old and <60 years old, and have been
amenorrhoeic for 12 months with the results of follicle stimulating hormone
examination were in the postmenopausal reference range per testing hospital.
12. Subject with good compliance and willing to have the follow-up visits
Exclusion Criteria:
1. Subject has symptomatic, uncontrolled brain or pia mater metastasis. If subject has
known and treated brain metastasis, baseline CT or MRI data within 4 weeks prior to
randomization are mandatory to be obtained. Subject should have received brain
metastasis treatment for at least four weeks before randomization. If subject needs to
use steroids for treatment after randomization, the dosage of steroids (<10 mg/day
prednisone or equivalent) should be stable before randomization for at least four
weeks without relevant neurological symptoms
2. Subject has third interstitial effusion (e.g. massive pleural and ascites) that cannot
be controlled by drainage or other means.
3. Subject has local or systemic anti-tumor treatment within 2 weeks prior to
randomization, including radiotherapy, chemotherapy, surgical resection (major surgery
for breast cancer), or target therapy, and endocrine therapy for anti-tumor within 7
days prior to randomization.
4. Subject has any investigational treatment within 4 weeks prior to randomization
(including margetuximab)
5. Subject has history of major surgery with unrecovered surgical effect within 4 weeks
prior to randomization.
6. Subject has other malignant tumor (complete cured in situ cervical cancer, cutaneous
basal cell carcinoma or cutaneous squamous cell carcinoma are not included) within 5
years prior to randomization.
7. Subject has severe and uncontrolled disease, including but not limited to
- Uncontrollable nausea and vomiting, and any other severe gastrointestinal
disorders
- Active viral infections, e.g. human immunodeficiency virus (HIV), hepatitis B
(HBV; HbsAg positive, HBV-DNA (=103 copies/ml or (=500 IU/ml), hepatitis C (HCV)
etc.
- Severe uncontrollable diabetes, hypertension, thyroid diseases etc.
- Severe uncontrollable pulmonary diseases, e.g. severe contagious pneumonia,
interstitial lung disease etc.
- Myocardial infarction, unstable angina pectoris, stroke, transient ischemic
attack within 6 months prior to randomization; clinically significant arrhythmia,
congestive heart failure (NYHA II-IV), pericarditis or severe pericardial
effusion, myocarditis, etc.
8. Subject has known allergy to recombinant proteins, polysorbide 80, benzyl alcohol or
any excipients contained in manufacturing of margetuximab, trastuzumab or other study
treatments. For subject with previous transfusion reactions to trastuzumab or other
monoclonal antibodies, if there is no contraindication for trastuzumab treatment, the
subject is eligible for enrollment.
9. Subject has contraindication of using trastuzumab, or confounding disease that may
prevent subject from using chemotherapy prescribe by the investigator.
10. Subject has vaccination with any live virus vaccine within four weeks prior to
randomization; inactivated influenza vaccine is allowed.
11. Subject who is pregnant or breastfeeding, or who is expected to be pregnant during the
period of the study
12. Dementia or any mental condition may impede understanding and informed consent
13. Any disease, treatment, or laboratory abnormalities that may interfere with the
results of the study, affect the subject's full participation in the study, or that
the investigator does not consider that the subject is appropriate to participate in
the study
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