| Eligibility |
Inclusion Criteria:
1. Voluntary agreement to provide written informed consent;
2. Aged 18 to 75 years, male or female;
3. Patients with unresectable locally advanced, relapsed, or metastatic breast cancer
confirmed by histology or cytology;
4. Received at least 2 lines of systemic anti-HER2 therapy for unresectable locally
advanced, recurrent, or metastatic disease, and one of which is a
trastuzumab-containing regimen, progression during or within 12 months of the end of
prior (neo)adjuvant anti-HER2 therapy is considered one line of therapy.
5. Radiographic evidence of disease progression confirmed by the investigator during or
after the most recent systemic treatment;
6. Sufficient tumor samples within 3 years are available for central lab to confirm the
HER2 status;
7. Confirmed to be HER2 positive by central lab (HER2-positive is defined as IHC 3+ or
IHC 2+ with ISH positive);
8. At least one measurable target lesion at the baseline according to the RECIST v1.1;
9. The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
10. Left ventricular ejection fraction (LVEF) =50% of normal in echocardiogram (ECHO) or
multi-gate detection scan (MUGA) within 4 weeks before the first administration of
study drug;
11. The function of major organs must meet the following criteria within 7 days before
enrollment (have not received blood transfusion, G-CSF, other hematopoietic
stimulating factors or medical supportive treatments within 14 days before the first
dose of study drug): absolute neutrophil count (ANC) =1.5×10^9 /L; platelet (PLT)
=100×10^9 /L; hemoglobin =90 g/L; international normalized ratio (INR) or prothrombin
time (PT) =1.5×the upper limit of normal (ULN) (not receiving anticoagulation), or
patients receiving anticoagulation need to be within treatment target range and at a
stable dose; activated partial thromboplastin time (APTT) =1.5×ULN; creatinine
clearance rate>60 mL/min (calculated by Cockcroft-Gualt formula); total bilirubin
=1.5×ULN, or =3×ULN for patients with Gilbert's syndrome; aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) =2.5×ULN, or =5×ULN for patient with liver
metastasis;
12. Life expectancy = 3 months;
13. Women of childbearing age must have a negative pregnancy test prior to study entry;
14. Female and male patient of childbearing age must agree to take adequate contraceptive
measures during the entire study period and through at least 6 months after the last
dose of study drug.
Exclusion Criteria:
1. Pregnant or breastfeeding women;
2. History of DP303c treatment;
3. History of any other malignant tumors within five years (except for skin basal cell
carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical cancer
in situ and other in situ tumors that have received radical resection and have not
recurred);
4. Has not recovered from adverse reactions caused by previous anti-tumor treatments to =
grade 1 or baseline (refer to NCI CTCAE 5.0) (except for adverse reaction such as
alopecia, pigmentation disorder and others which have no safety risk evaluated by the
investigator);
5. Patients have received other clinical trial drugs within 4 weeks before the first dose
of study drug (for small molecule targeted drugs, this time interval is required to be
2 weeks or 5 half-lives, whichever is longer);
6. Cytotoxic chemotherapy, radiotherapy and immunotherapy and other anti-tumor treatments
within 4 weeks before the first dose of study drug; endocrine therapy and Chinese
medicine treatments with anti-tumor indications within 2 weeks; or oral fluorouracil
and small molecule targeted drugs within 2 weeks or 5 half-lives, whichever is longer;
7. Radical radiation therapy within 4 weeks before the first dose of study drug or
palliative radiation therapy within 2 weeks before the first dose of study drug;
8. Underwent major surgery within 4 weeks and did not fully recover before the first dose
of study drug;
9. The cumulative amount of previous exposure to anthracyclines has reached the following
dosage: doxorubicin or liposomal doxorubicin >360 mg/m^2; epirubicin >720 mg/m^2;
mitoxantrone>120 mg/m^2; idarubicin >90 mg/m^2; or other anthracyclines > 360 mg/m^2
of doxorubicin equivalent;
10. Untreated (including baseline findings) or unstable cerebral parenchymal metastasis,
spinal cord metastasis or compression, and cancerous meningitis.
11. History of LVEF < 40%, symptomatic congestive heart failure (CHF), or associated
toxicity leading to permanent discontinuation during previous treatments of
trastuzumab or a drug containing a trastuzumab-like structure.
12. Serious or uncontrolled cardiovascular disease;
13. Serious or uncontrolled lung disease;
14. Symptomatic ascites or pleural effusion; patients who are clinically stable for at
least 1 week after local treatment (including therapeutic pleural or abdominal
puncture) are admitted;
15. Patients who currently have corneal diseases that require medication or surgical
intervention, or have a history of serious corneal diseases, or are unwilling to stop
wearing contact lenses during the study;
16. Peripheral neuropathy = grade 2 (refer to NCI CTCAE 5.0) or history of = grade 3
neurotoxicity (refer to NCI CTCAE 5.0);
17. Uncontrollable electrolyte imbalances include hypokalemia, hypocalcemia or
hypomagnesemia (refer to NCI CTCAE 5.0, =2 grade);
18. Active infections requiring intravenous antibiotics, antivirals, or antifungals within
2 weeks before the first dose of study drug;
19. Active hepatitis B or C (HBsAg positive with HBV DNA >ULN, but patients with HBV DNA
titer < 500 IU/mL after anti-HBV treatment could be enrolled; HCVAb positive with HCV
RNA> ULN).
20. History of immunodeficiency diseases, including human immunodeficiency virus (HIV)
positive;
21. Conditions requiring treatments with systemic corticosteroids or other
immunosuppressive drugs within 2 weeks before the first dose of study drug, except for
topical, ocular, intra-articular, intranasal, or inhaled corticosteroid therapy;
22. History of allergy to any components of study drug;
23. History of serious hypersensitivity to other monoclonal antibodies;
24. Suffering from a known mental illness, severe mental illness or poor compliance;
25. Treated with strong CYP3A inhibitors or strong CYP3A inducers within 14 days before
the first dose of study drug;
26. Any disorders, treatments, or abnormalities in laboratory tests that may affect the
overall treatments of patients in the study, increase the risk of patients, or
interfere with the study results; or the investigator believes that participation in
the study is not in the patient's best interest.
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