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 70 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.
• Aged ≥ 18 years.
• Histologically confirmed unresectable locally advanced or metastatic breast cancer, with immunohistochemistry (IHC) results indicating HER2-positive (IHC 3+; or IHC 2+ and FISH-positive) or HER2-low expression (IHC 1+; or IHC 2+ and FISH-negative).
• Prior treatment meeting one of the following criteria:
‣ 1 For HER2-positive breast cancer, patients must have received at least one prior anti-HER2 targeted therapy.
‣ 2 For HER2-low breast cancer, patients must have received at least one prior line of systemic therapy for metastatic disease, or have relapsed within 6 months during or after completion of adjuvant chemotherapy.
• ECOG Performance Status of 0 or 1.
• Evidence of radiographic or objective disease progression at or after the last systemic therapy prior to initiating study treatment.
• Anticipated life expectancy ≥ 12 weeks at screening.
• At least one measurable lesion that has not been previously irradiated, with a longest diameter ≥ 10 mm as accurately measured by CT or MRI at baseline (except for lymph nodes, which must have a short axis ≥ 15 mm). Alternatively, if only bone lesions are present, evaluable osteolytic or mixed osteolytic/blastic bone lesions as assessed by CT, MRI, or X-ray are acceptable.
• 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 parameters listed below, the most recent results must be used to meet the inclusion criteria:
∙ Hemoglobin ≥ 9 g/dL;
‣ Absolute Neutrophil Count (ANC) ≥ 1500/mm3;
‣ Platelet count ≥ 100,000/mm3;
‣ Total bilirubin (TBL) ≤ 1.5 × Upper Limit of Normal (ULN) at baseline in the absence of liver metastases; or \< 3 × ULN in the presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases;
‣ ALT and AST ≤ 3 × ULN; or \< 5 × ULN for patients with liver metastases;
‣ Serum albumin ≥ 2.5 g/dL;
‣ Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula);
‣ International Normalized Ratio (INR) or Prothrombin Time (PT), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN.
⁃ Female patients must not donate eggs or collect eggs for personal use from the screening period throughout the study treatment period and for 7 months after the last dose of study treatment. Breastfeeding should be avoided during this period. If oocyte preservation is desired, it should be considered prior to randomization in this study.