Disitamab vedotin plus bevacizumab for HER2-low metastatic breast cancer after T‑DxD failure

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 study will try disitamab vedotin combined with bevacizumab in adults with HER2‑low metastatic breast cancer whose disease progressed after trastuzumab deruxtecan.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: trastuzumab, bevacizumab, disitamab, radiation
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07446452 on ClinicalTrials.gov

What this trial studies

This is a multicenter, single‑arm phase II trial enrolling adults with HER2‑low (IHC 1+ or 2+/ISH‑) advanced or metastatic breast cancer who progressed after prior trastuzumab deruxtecan (T‑DxD). Participants receive disitamab vedotin (RC48) plus bevacizumab per protocol, with tumor response reviewed by an independent committee. The primary endpoint is objective response rate (ORR); secondary endpoints include progression‑free survival, overall survival, disease control rate, and duration of response. Safety is monitored continuously and graded using CTCAE v5.0 with dose modifications and supportive care as needed.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed HER2‑low metastatic or recurrent breast cancer who have received prior T‑DxD, have at least one measurable lesion, ECOG 0–2, expected survival >3 months, and adequate organ function are ideal candidates.

Not a fit: Patients with uncontrolled serious comorbidities, clinically uncontrolled effusions, low cardiac function (LVEF <50%), or those who have not received prior T‑DxD or do not meet HER2‑low criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could offer a new treatment option that shrinks tumors or delays progression for patients with HER2‑low disease after T‑DxD.

How similar studies have performed: Antibody‑drug conjugates including disitamab vedotin have shown activity in HER2‑expressing tumors, but combining RC48 with bevacizumab after T‑DxD failure is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Signed written informed consent prior to any study-related procedures.
2. Female or male participants aged 18 years or older.
3. Histologically or cytologically confirmed advanced or recurrent/metastatic HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-).
4. Received at least two cycles of trastuzumab deruxtecan (T-DXd) during treatment for recurrent or metastatic disease.
5. 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.
6. ECOG performance status 0-2.
7. Expected survival time \>3 months.
8. Left ventricular ejection fraction (LVEF) ≥50% by ECHO or MUGA within 4 weeks prior to the first dose.
9. Adequate organ function as determined by laboratory assessments per investigator's judgment.

Exclusion Criteria:

1. Uncontrolled comorbid conditions.
2. Clinically uncontrolled pleural effusion, ascites, or pericardial effusion requiring drainage within 2 weeks prior to enrollment.
3. History or current evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
4. Use of systemic immunosuppressive medications within 14 days prior to the first dose.
5. Clinically significant pulmonary comorbidities.
6. Allogeneic organ transplantation or hematopoietic stem cell transplantation (except corneal transplant).
7. Known hypersensitivity to bevacizumab, disitamab vedotin, or any of their components or excipients.
8. Spinal cord compression or clinically active central nervous system (CNS) metastases.
9. Unresolved toxicities or complications from prior therapy that have not recovered to baseline or ≤Grade 1 (per CTCAE v5.0).
10. Known human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive).
11. Untreated active hepatitis B infection.
12. Active hepatitis C virus (HCV) infection.
13. Receipt of a live vaccine within 30 days before Cycle 1 Day 1.
14. Pregnant or breastfeeding women.
15. Any severe or uncontrolled systemic disease judged by the investigator to interfere with study participation or safety evaluation.
16. 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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Li, Ph.D

Conditions HER2-low Breast Cancer; Disitamab Vedotin; Bevacizumab; Trastuzumab deruxtecan failure