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

Inclusion criteria

• 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.

Exclusion criteria

• Uncontrolled comorbid conditions.
• Clinically uncontrolled pleural effusion, ascites, or pericardial effusion requiring drainage within 2 weeks prior to enrollment.
• History or current evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
• Use of systemic immunosuppressive medications within 14 days prior to the first dose.
• Clinically significant pulmonary comorbidities.
• Allogeneic organ transplantation or hematopoietic stem cell transplantation (except corneal transplant).
• Known hypersensitivity to bevacizumab, disitamab vedotin, or any of their components or excipients.
• Spinal cord compression or clinically active central nervous system (CNS) metastases.
• Unresolved toxicities or complications from prior therapy that have not recovered to baseline or ≤Grade 1 (per CTCAE v5.0).
• Known human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive).
• Untreated active hepatitis B infection.
• Active hepatitis C virus (HCV) infection.
• Receipt of a live vaccine within 30 days before Cycle 1 Day 1.
• Pregnant or breastfeeding women.
• Any severe or uncontrolled systemic disease judged by the investigator to interfere with study participation or safety evaluation.
• Gastrointestinal perforation or fistula, wound dehiscence requiring medical intervention, wound-healing complications, severe hemorrhage, arterial thrombotic events, or life-threatening (Grade 4) venous thromboembolism, including pulmonary embolism.