A Phase II Clinical Study to Evaluate the Efficacy and Safety of Disitamab Vedotin in Combination With Bevacizumab in Patients With HER2-Low Metastatic Breast Cancer After Progression on Prior T-DXd Therapy
This is a multicenter, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of disitamab vedotin in combination with bevacizumab in patients with HER2-low advanced or metastatic breast cancer who have experienced disease progression following prior T-DXd therapy. Eligible patients must have HER2-low expression (IHC 1+ or 2+/FISH-) and have previously received T-DXd. Participants will receive RC48 (disitamab vedotin) plus bevacizumab according to the study protocol. Treatment-related adverse events will be closely monitored and managed, with severity graded according to CTCAE v5.0 criteria. Supportive care or dose adjustments will be implemented as necessary. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR), all of which will be evaluated by an independent review committee. Safety assessments will include the incidence, severity, management, and outcomes of adverse events. Patient-reported quality of life will be evaluated using the EORTC QLQ-C30 questionnaire at predefined intervals. In addition, this study will conduct exploratory multi-omics translational research to investigate the potential molecular mechanisms underlying treatment response and resistance, and to identify predictive biomarkers associated with clinical outcomes. The ultimate goal is to assess the therapeutic efficacy and safety of this regimen, and to develop predictive models that may help identify HER2-low patients most likely to benefit, thereby supporting precision and individualized treatment strategies.
• Signed written informed consent prior to any study-related procedures.
• Female or male participants aged 18 years or older.
• Histologically or cytologically confirmed advanced or recurrent/metastatic HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-).
• Received at least two cycles of trastuzumab deruxtecan (T-DXd) during treatment for recurrent or metastatic disease.
• At least one measurable lesion according to RECIST version 1.1. A lesion within a previous radiation field may be considered measurable if disease progression is confirmed at that site.
• ECOG performance status 0-2.
• Expected survival time \>3 months.
• Left ventricular ejection fraction (LVEF) ≥50% by ECHO or MUGA within 4 weeks prior to the first dose.
• Adequate organ function as determined by laboratory assessments per investigator's judgment.