| Eligibility |
Inclusion Criteria:
1. Understanding and voluntarily signing the informed consent form;
2. Female, age = 18 years and <65 years;
3. Histopathologically and molecular pathologically confirmed HR positive, HER2 negative
breast cancer (based on the latest test result);
Notes:
Positive HR is defined as positive estrogen receptor (ER), negative or positive
progesterone receptor (PR) (=1% positive stained cells will be regarded as positive
receptor); Negative HER2: negative immunohistochemical (IHC) result (0, 1+), or IHC
result 2+ and negative result of in situ hybridization (ISH) amplification;
4. Progression after endocrine therapy, being suitable for late-stage rescue
chemotherapy, including the following conditions (meeting any one of them):
Primary endocrine resistance: recurrence less than two years after adjuvant endocrine
therapy, or progression of disease less than 6 months after late-stage 1st-line
endocrine therapy. For the patients with primary endocrine resistance, no use of other
systematic therapy except endocrine therapy in relapsed/progressive period (the
combined use of CDK4/6 inhibitor, Everolimus or HDAC inhibitor with endocrine therapy
is allowed). There were no more than 2 lines of systemic therapy for advanced disease
previously.
Secondary (acquired) endocrine resistance: recurrence more than 2 years after adjuvant
endocrine therapy and within one year after discontinuation of it, or progression of
disease =6 months after late-stage 1st-line endocrine therapy. For the patients with
secondary (acquired) endocrine resistance, at least 1 line but no more than 3 lines of
endocrine therapy for advanced disease are recommended (the combined use of CDK4/6
inhibitor, Everolimus or HDAC inhibitor with endocrine therapy is allowed), and the
number of lines will not be calculated for adjuvant endocrine therapy. There were no
more than 3 lines of systemic therapy for advanced disease previously.
5. No use of chemotherapy for recurrent/metastatic breast cancer;
6. At least one extracranial measurable lesion (RECIST 1.1);
7. Peripheral blood absolute monocyte count (AMC) <0.25×109/L (tested by local
laboratory, it is allowed to be repeated once if the AMC is ranged from
0.25~0.35×109/L at screening);
8. Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-1;
9. Expected survival =3 months;
10. Recovery of toxicity induced by previous therapy (except alopecia) to grade 1
(National Cancer Institute - Common Terminology Criteria for Adverse Events version
5.0 [NCI CTCAE v5.0]) or normal level;
11. Good organ function within 1 week prior to the first dose of study drug:
Hematology: no transfusion of platelet or any growth factor within 7 days prior to the
screening visit, white blood cell count =3×109/L, absolute neutrophil count (ANC)
=1.5×109/L, platelet count =100×109/L, hemoglobin =90 g/L; Hepatic function: serum
total bilirubin =1.5× upper limit of normal (ULN), or total bilirubin =3×ULN in case
of Gilbert's syndrome; aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) =2.5×ULN, or AST and ALT=5×ULN in case of hepatic metastasis; Renal function:
serum creatinine =1.5×ULN.
12. The female subjects of childbearing potential must have negative pregnancy test within
1 week prior to the first dose of study drug, and they and their spouses agree to take
effective contraceptive measures during the study and within 6 months after the last
dose
Exclusion Criteria:
1. Known uncontrollable or symptomatic central nervous system metastasis, including brain
metastasis or meningeal metastasis, or symptoms suggestive of cancerous meningitis,
leptomeningeal disease and/or progressive growth. Patients with a history of central
nervous system metastasis or spinal cord compression are allowed to be enrolled if
they have received definite local treatment (e.g., radiotherapy, surgical therapy),
have discontinued anticonvulsant drugs and steroids for at least 4 weeks prior to the
first dose of study drug and have stable clinical manifestations;
2. Previous use of high-dose chemotherapy plus hemopoietic stem cell transplantation;
3. Grade 4 operation performed within 4 weeks prior to the first dose of study drug, or
grade 2 or 3 operation performed within 7 days prior to the first dose of study drug;
4. Abnormal thyroid function that is poorly controlled after treatment;
5. Chemotherapy, endocrine therapy or treatment with other investigational product within
4 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer);
or radiotherapy within 2 weeks prior to the first dose of study drug (except the
palliative radiotherapy for non-target lesion, enrollment will be allowed if the
toxicity is resolved);
6. Serious or uncontrolled heart disease (New York Heart Association [NYHA] grade III-IV)
within 6 months prior to the first dose of study drug, including myocardial
infarction, severe/unstable angina pectoris, =grade 2 persistent arrhythmia in
accordance with NCI CTCAE v5.0, atrial fibrillation of any grade, coronary/peripheral
artery bypass grafting, symptomatic congestive heart failure; or presence of
cerebrovascular accident, including transient ischemic attack, symptomatic pulmonary
embolism, etc.;
7. Presence of other malignant tumors within 5 years prior to the first dose of study
drug (except for basal cell or squamous cell carcinoma of skin, superficial bladder
cancer and carcinoma in situ of cervix, which have been cured);
8. Other concomitant disease seriously hazardous to patient's safety or affecting
completion of the study as judged by investigators, except for tumor;
9. Presence of one of the following conditions: active infection considered by
investigators that may affect patient's participation in the study or the study
results; positive hepatitis B surface antigen, and hepatitis B virus (HBV) DNA copy >
ULN (patients with HBV DNA copy reduced to normal range after antiviral therapy are
allowed to be enrolled); positive hepatitis C virus antibody and hepatitis C virus
(HCV) RNA copy >ULN; positive human immunodeficiency virus (HIV); or any serious
infection requiring systematic treatment within 4 weeks prior to the first dose of
study drug;
10. Clinically significant abnormality indicated on electrocardiography (ECG), including
but not limited to serious arrhythmia, prolonged QT interval (QTcF>470 ms,
QTcF=QT/RR0.33); or presence of various conditions that may increase the risk of
prolonged QT interval, e.g., known history of prolonged QTc, congenital long QT
syndrome, Brugada syndrome, torsade de pointes, uncontrollable electrolyte disorder
(e.g., calcemia, hypokalaemia and hypomagnesaemia, etc.);
11. Previous diagnosis of autoimmune disease or requiring long-term use of systemic
corticosteroids (dose >10 mg/day prednisone or equivalent) or other immunosuppressants
within 4 weeks prior to the first dose of study drug; however, patients are allowed to
be enrolled in the following conditions: in the absence of active autoimmune disease,
inhaled or topical steroids, or adrenaline replacement therapy at the dose =10 mg/day
Prednisone equivalent is allowed to be used;
12. Treatment with systematic immunostimulatory drugs (including but not limited to
interferon-a (IFN-a) and interleukin 2 (IL-2)) within 6 weeks or 5 half-lives prior to
the first dose of study drug (whichever comes later);
13. Vaccination with live attenuated vaccine, protein vaccine, mRNA or DNA vaccine within
4 weeks prior to the first dose of study drug, or expected to receive the above
vaccines during the study;
14. Previous allergy to macromolecular protein preparation or protein, or Quincke's edema
(also known as angioneurotic edema), or known allergy to any component of the study
drug;
15. History of clear mental disorder, or history of psychotropic drug abuse, drug
addiction or alcohol abuse;
16. Received organ transplant;
17. Women who are pregnant or breastfeeding;
18. Having participated in any other drug clinical trial within 4 weeks prior to the first
dose of study drug or currently receiving treatment in other clinical trials (except
those who are participating in the follow-up of overall survival in one study);
19. Patients with other conditions that are not suitable to participate in the clinical
trial, as considered by the investigator.
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