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

Inclusion criteria

• Aged ≥ 18 years old.
• 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.
• Patients with advanced breast cancer who have received no more than 2 lines of prior systemic therapies.
• Expected survival time ≥ 4 months.
• Have at least one measurable lesion per RECIST 1.1 criteria (helical CT scan lesion diameter ≥ 10 mm with slice thickness ≤ 5 mm).
• Adequate major organ function without blood transfusion.
• Voluntarily participate in the study, sign informed consent form, with good compliance and willingness to complete follow-up visits.

Exclusion criteria

• Prior treatment with anti-HER2 antibody-drug conjugates (ADC).
• Known leptomeningeal metastasis or active brain metastasis.
• 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.
• Major surgery or severe trauma within 4 weeks before enrollment, or planned major surgery during the study period.
• Participation in other investigational new drug clinical trials within 4 weeks prior to enrollment.
• Presence of hereditary bleeding tendency or coagulation disorders.
• Uncontrolled hypertension with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg despite standard antihypertensive therapy.
• 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).
• 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.
• Conditions affecting drug intake and absorption, such as dysphagia, chronic diarrhea and intestinal obstruction.
• Known allergy to any component of the study drugs.
• Uncontrolled pleural effusion or ascites that cannot be relieved by drainage or other clinical interventions.
• 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.
• Any other conditions considered inappropriate for study enrollment by the investigator.