RecruitingPhase 2NCT07446452

Disitamab Vedotin Plus Bevacizumab in HER2-Low Metastatic Breast Cancer After T-DXd Failure: A Phase II Study

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

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Enrollment

37 participants

Start Date

Jan 1, 2024

Study Type

INTERVENTIONAL

Conditions

HER2-low Breast Cancer

Summary

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.

Eligibility

Sex: FEMALEMin Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This Phase II trial is testing a combination of two cancer drugs — disitamab vedotin and bevacizumab — in people with HER2-low metastatic breast cancer (a specific type of breast cancer with low levels of HER2 protein) who have already been treated with another drug called trastuzumab deruxtecan (T-DXd) and whose cancer has continued to grow or spread. **You may be eligible if:** - You are 18 or older (male or female) - You have been diagnosed with advanced or metastatic HER2-low breast cancer (confirmed by lab testing) - You have received at least two cycles of T-DXd and your cancer has progressed - Your cancer has at least one measurable tumor on imaging - You have good general health (ECOG performance status 0–2) - Your heart function is adequate (ejection fraction ≥50%) **You may NOT be eligible if:** - You have uncontrolled fluid buildup around your lungs or heart - You have a history of lung inflammation (interstitial lung disease) - You have had an organ transplant (except corneal transplant) - You are taking immune-suppressing medications - You have a known allergy to bevacizumab or disitamab vedotin Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGDisitamab Vedotin (RC48)

A HER2-targeted antibody-drug conjugate comprising a humanized anti-HER2 monoclonal antibody linked via a cathepsin-cleavable MC-VC-PAB linker to the microtubule inhibitor MMAE (drug-to-antibody ratio ≈4). Administered intravenously at 2.0 mg/kg every 2 weeks.

DRUGBevacizumab

A recombinant humanized monoclonal antibody that binds vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis. Administered intravenously at 5 mg/kg every 2 weeks in combination with RC48.