A Phase II, Single-Arm, Single-Center, Prospective Study of SKB264 Plus Inetetamab in HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer Patients Progressing After T-DXd Treatment
This is a prospective, single-arm, single-center, Phase II clinical study designed to assess the preliminary efficacy and safety of SKB264 Plus Inetetamab plus inetetamab for the treatment of HER2-positive, unresectable, locally advanced or metastatic breast cancer following progression on prior T-DXd therapy.
• Age ≥ 18 years, male or female.
• Patients with histologically or cytologically confirmed breast cancer who meet the following criteria:
‣ Unresectable locally advanced or metastatic breast cancer.
⁃ Pathologically confirmed HER2-positive breast cancer, regardless of hormone receptor (HR) status. HER2 positivity is defined as: IHC 3+, or IHC 2+ and FISH positive.
⁃ Prior treatment for unresectable locally advanced or metastatic disease must have included the following anti-HER2 therapies: trastuzumab deruxtecan (T-DXd) and trastuzumab (or a trastuzumab biosimilar). Patients who received T-DXd and trastuzumab (or a biosimilar) in the (neo)adjuvant setting and experienced recurrence or metastasis during or within 12 months of completing therapy are eligible. Additionally, prior treatment regimens must have included a taxane.
⁃ Documented disease progression or unacceptable toxicity after the last line of therapy for unresectable locally advanced or metastatic disease.
• ECOG performance status of 0-2, with a life expectancy of \> 3 months.
• At least one measurable target lesion according to RECIST v1.1 criteria.
• Adequate organ and bone marrow function, as defined below:
‣ Complete Blood Count: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L; Hemoglobin ≥ 90 g/L.
⁃ Liver Function: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN. For patients with liver metastases, ALT and AST ≤ 5.0 × ULN.
⁃ Renal Function: Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
⁃ Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 × ULN and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
⁃ Echocardiogram: Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
⁃ 12-lead ECG: QT interval corrected by Fridericia's formula (QTcF) \< 470 ms for females and \< 450 ms for males.
• Voluntarily agrees to participate in the study by signing the informed consent form (ICF), and is willing and able to comply with follow-up procedures.