A Single-Center, Single-Arm, Open-Label Phase II Study of SHR-A1811 in Patients With Advanced Breast Cancer With Ultra-Low HER2 Expression
This is a single-center, single-arm, open-label phase II exploratory study. A total of 30 patients aged 18-75 years with ECOG PS 0-1, pathologically confirmed advanced breast cancer with ultra-low HER2 expression will be enrolled. Eligible patients must have at least one measurable lesion and have received 1-2 lines of prior systemic therapy for advanced disease. All participants receive intravenous SHR-A1811 at 4.8 mg/kg every 3 weeks, until disease progression, intolerable adverse events or other discontinuation criteria. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), and safety profile.
• Female subjects, aged ≥18 years and ≤75 years;
• ECOG performance status 0-1;
• Expected survival of no less than 3 months;
• Histologically documented breast cancer:
∙ Advanced or metastatic breast cancer
‣ History of ultra-low HER2 expression: histopathology confirms ultra-low HER2 expression, defined as incomplete, faint membranous staining in ≤10% of invasive tumor cells.
⁃ If multiple historical/local HER2 test results are available for a subject, the most recent result derived from metastatic or advanced disease should be adopted.
• If local HER2 testing only classifies the subject's tumor as HER2-negative without available IHC status, the result must be re-confirmed by the Department of Pathology of Tianjin Medical University Cancer Institute and Hospital.
• Have radiographic or objective evidence of disease progression at or after the last prior systemic therapy before initiation of study treatment;
• For hormone-receptor-positive breast cancer: subjects have received 1-2 lines of endocrine therapy in the advanced-disease setting. Progression during adjuvant endocrine therapy or within 12 months after completion of adjuvant endocrine therapy counts as 1 prior line;
• For hormone-receptor-negative breast cancer: subjects have received 1-2 lines of prior systemic therapy. Progression during adjuvant therapy or within 12 months after completion of adjuvant therapy counts as 1 prior line;
• Have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1;
• Adequate major organ and bone marrow function meeting the following criteria:
∙ . Hemoglobin ≥90 g/L (no blood transfusion within 14 days);
‣ . Absolute neutrophil count ≥1.5×10⁹/L;
‣ . Platelet count ≥90×10⁹/L;
‣ . Total bilirubin ≤1.5 × upper limit of normal (ULN);
‣ . Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; in the presence of liver metastases, ALT and AST ≤5 × ULN;
‣ . Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (calculated by the Cockcroft-Gault formula);
‣ . International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN;
‣ . Left ventricular ejection fraction (LVEF) ≥50%; QTc interval \<470 ms for female subjects;
⁃ Female subjects of child-bearing potential must agree to use highly effective contraception from study screening through 7 months after the last dose of study drug and agree not to breast-feed. A negative serum pregnancy test must be obtained within 7 days prior to the first study drug administration;
⁃ No radiotherapy, chemotherapy, molecular-targeted therapy, immunotherapy or surgery within 4 weeks prior to enrollment; toxicities from prior therapies have recovered to Grade ≤1 (wounds fully healed if surgery was performed). No endocrine therapy within 14 days prior to enrollment.
⁃ Subjects voluntarily participate in the study and provide written informed consent, with anticipated good compliance to follow protocol-required study procedures.