Study on Using HER2-PET to Predict the Efficacy of T-DXd Treatment in Advanced Breast Cancer and to Investigate the Heterogeneity of HER2 Expression
The study will be conducted as an open-label, single-center, Phase II clinical study, with a planned enrollment of 86 patients with locally advanced or metastatic HER2-positive and HER2-low breast cancer who are intended to receive at least two cycles of T-DXd monotherapy. All patients receiving T-DXd treatment must meet current clinical indications. After screening and enrollment, participants will undergo FDG-PET scans and free-of-charge HER2-PET scans prior to T-DXd treatment, with tissue biopsies performed as needed. Participants will receive single-agent T-DXd treatment until disease progression, with additional tissue biopsies performed as needed.This study will integrate and analyze patients' baseline clinical characteristics, treatment efficacy, and prognostic information, along with HER2 expression levels and HER2 expression heterogeneity as assessed by HER2-PET, to evaluate the feasibility of guiding T-DXd treatment in patients with advanced breast cancer.
⁃ Age ≥ 18 years.
⁃ Histopathologically confirmed unresectable locally advanced or metastatic breast cancer, with documented prior immunohistochemistry (IHC) results indicating HER2-positive (IHC 3+, or IHC 2+ with positive FISH) or HER2-low (IHC 1+, or IHC 2+ with negative FISH) expression.
⁃ For patients with hormone receptor-positive (HR+), HER2-negative breast cancer, patients must have received prior treatment with a CDK4/6 inhibitor in the locally advanced or metastatic setting, or experienced disease recurrence during adjuvant intensified CDK4/6 inhibitor therapy or within 12 months after completing adjuvant intensified CDK4/6 inhibitor therapy. (HR-positive is defined as ≥ 1% of tumor cells demonstrating positive ER staining by IHC; HER2-negative is defined as IHC score 0 or 1+, or IHC score 2+ with no evidence of in situ hybridization \[ISH\] gene amplification, or no evidence of ISH gene amplification in the absence of an IHC test.)
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
⁃ Documented radiological or objective evidence of disease progression on or after the most recent line of systemic therapy prior to initiating study treatment.
⁃ Life expectancy ≥ 12 weeks at the time of screening.
⁃ Presence of at least one lesion (measurable and/or non-measurable) that can be accurately evaluated at baseline by CT (or MRI if CT is contraindicated) and is suitable for repeated assessment according to RECIST v1.1.
⁃ Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to randomization.
⁃ Adequate organ and bone marrow function within 14 days prior to randomization. For all laboratory parameters listed below, the most recently obtained values must meet the eligibility criteria:
• Hemoglobin ≥ 9.0 g/dL;
• Absolute neutrophil count (ANC) ≥ 1,500/mm³;
• Platelet count ≥ 100,000/mm³;
• At baseline, total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) in the absence of liver metastases, or \< 3.0 × ULN in the presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) or documented liver metastases;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN (\< 5.0 × ULN for patients with liver metastases);
• Serum albumin ≥ 2.5 g/dL;
• Creatinine clearance (CrCl) ≥ 30 mL/min (calculated using the Cockcroft-Gault formula);
• International Normalized Ratio (INR) or prothrombin time (PT), and partial thromboplastin time or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
⁃ Female patients must refrain from donating eggs (oocytes) or retrieving/banking eggs for personal use from the screening period, throughout the entire study treatment period, and for at least 7 months after the final dose of study treatment. Breastfeeding must be discontinued during this period. Patients wishing to preserve eggs/fertility should consider undergoing these procedures prior to randomization in this study.