Exploratory Study of SHR-A1811 Via Different Administration Routes in Patients

• SHR-A1811 (Drug): SHR-A1811 administered weekly
• SHR-A1811 (Drug): SHR-A1811 administered every two weeks (q2w)
• SHR-A1811 (Drug): SHR-A1811 administered every three weeks (q3w)

Primary outcomes

• Objective Response Rate (ORR) [From enrollment until disease progression or up to 2 years]: Defined as the proportion of patients who achieve confirmed complete response (CR) or partial response (PR) to the study treatment, assessed per RECIST 1.1 criteria.

Secondary outcomes

• Progression-Free Survival (PFS) [From enrollment until disease progression or up to 2 years]: Defined as the time from study enrollment to the first documentation of disease progression (per RECIST 1.1) or all-cause death, whichever occurs first.

Other outcomes

• Overall Survival (OS) [From enrollment until all-cause death.]: Defined as the time from study enrollment to all-cause death.
• Safety and Tolerability [From first dose of study drug up to 30 days after last dose]: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Aged ≥ 18 years old.
2. Pathologically confirmed HER2-positive advanced breast cancer. HER2 positivity is defined as IHC 3+ in >10% immunoreactive cells or HER2 gene amplification confirmed by in situ hybridization (ISH), which shall be verified by the pathology department of the participating center.
3. Patients with advanced breast cancer who have received no more than 2 lines of prior systemic therapies.
4. Expected survival time ≥ 4 months.
5. Have at least one measurable lesion per RECIST 1.1 criteria (helical CT scan lesion diameter ≥ 10 mm with slice thickness ≤ 5 mm).
6. Adequate major organ function without blood transfusion.
7. Voluntarily participate in the study, sign informed consent form, with good compliance and willingness to complete follow-up visits.

Exclusion Criteria:

1. Prior treatment with anti-HER2 antibody-drug conjugates (ADC).
2. Known leptomeningeal metastasis or active brain metastasis.
3. A history of other malignancies within the past 5 years, except for cured cervical carcinoma in situ, cutaneous basal cell carcinoma and squamous cell carcinoma. Malignancies cured solely by surgery more than 5 years prior to enrollment are allowed.
4. Major surgery or severe trauma within 4 weeks before enrollment, or planned major surgery during the study period.
5. Participation in other investigational new drug clinical trials within 4 weeks prior to enrollment.
6. Presence of hereditary bleeding tendency or coagulation disorders.
7. Uncontrolled hypertension with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg despite standard antihypertensive therapy.
8. A history of clinically significant pulmonary diseases, including but not limited to interstitial pneumonia, active pneumonia, pulmonary fibrosis and radiation pneumonitis (excluding asymptomatic post-radiation changes without treatment requirement).
9. A history of severe cardiac diseases or uncontrolled cardiac conditions, including NYHA class II or higher cardiac insufficiency, unstable angina, myocardial infarction within one year, and arrhythmias requiring clinical intervention.
10. Conditions affecting drug intake and absorption, such as dysphagia, chronic diarrhea and intestinal obstruction.
11. Known allergy to any component of the study drugs.
12. Uncontrolled pleural effusion or ascites that cannot be relieved by drainage or other clinical interventions.
13. Severe uncontrolled comorbidities, including immune deficiency disorders (e.g. HIV positivity, history of organ transplantation), active hepatitis B or hepatitis C, and severe ongoing infections requiring systemic anti-infective treatment.
14. Any other conditions considered inappropriate for study enrollment by the investigator.