Trastuzumab Deruxtecan With or Without Bevacizumab for HER2-low Unresectable and/or Metastatic Breast Cancer With Brain Metastasis: A Multicenter, Randomized, Open Label, Phase II Trial (THUMB Trial)
A phase II, open-label, multicenter, randomized controlled trial exploring the efficacy and safety of Trastuzumab Deruxtecan combined with or without Bevicizumab in HER2-low breast cancer with brain metastasis.
• ECOG score of 0 to 1.
• Expected survival period greater than 12 weeks.
• Histologically confirmed invasive HER2-low expressing breast cancer (specific definition: breast cancer patients with low expression of human epidermal growth factor receptor 2 (HER-2) as determined by pathological testing. Specifically: HER2 IHC 1+ or HER2 IHC++ with FISH/CISH negative. All specimens must be verified by the pathology department of the research participating center.
• Tumor stage: recurrent or metastatic breast cancer; local recurrence must be confirmed by the researcher to be unable to undergo radical surgical resection.
• Patients must have at least one lesion that has not previously received radiation therapy (measurable and/or non-measurable).
• MRI or CT shows brain metastasis and meets one of the following conditions:
• i) Untreated brain parenchymal metastasis found by imaging screening; ii) Previously locally treated stable or progressive brain parenchymal metastasis and meets one of the following conditions:a) Imaging stability ≥4 weeks; b) New brain parenchymal metastasis found by MR or CT.
• Received no more than 2 lines of chemotherapy after metastasis.
• HR-positive patients must have previously received CDK4/6 inhibitor treatment, whether in the adjuvant treatment phase or in the recurrent metastatic phase.
• Never used T-DXd or bevacizumab before.
⁃ The main organ functions are basically normal, meeting the following conditions:
⁃ Blood routine examination standards must comply with: HB≥90g/L (not transfused within 14 days); ANC≥1.5×10\^9/L; PLT≥75×10\^9/L;
⁃ Biochemical examination must comply with the following standards: TBIL≤1.5×ULN (upper limit of normal); ALT and AST≤3×ULN; if there is liver metastasis, ALT and AST≤5×ULN; serum Cr ≤1.5×ULN, endogenous creatinine clearance rate ≥30mL/min.
⁃ Allowed to use mannitol, hormone therapy before enrollment, but the drug treatment dose can be stable for at least one week without the need for an increase.
⁃ Female subjects with reproductive capacity need to use one medically recognized contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug.
⁃ Subjects voluntarily join this study, sign an informed consent form, have good compliance, and cooperate with follow-up.