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

February 28, 2026 updated by: The First Affiliated Hospital with Nanjing Medical University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Recruiting
        • The First Affiliated Hospital with Nanjing Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Disitamab Vedotin + Bevacizumab
Participants receive Disitamab Vedotin (RC48) at 2.0 mg/kg IV every 2 weeks plus Bevacizumab 5 mg/kg IV every 2 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or initiation of new anticancer therapy.
Drug: Disitamab 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.
Drug: Bevacizumab
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Objective Response Rate (ORR)
Time Frame: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From first dose to the date of radiographically confirmed disease progression or death, whichever occurs first, assessed up to 24 months.
From first dose to the date of radiographically confirmed disease progression or death, whichever occurs first, assessed up to 24 months.
Disease Control Rate (DCR)
Time Frame: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
Duration of Response (DOR)
Time Frame: From first documented tumor response (CR or PR) until disease progression or death, whichever occurs first, assessed up to 24 months.
From first documented tumor response (CR or PR) until disease progression or death, whichever occurs first, assessed up to 24 months.
Overall Survival (OS)
Time Frame: From first dose to the date of death from any cause, assessed up to 36 months.
From first dose to the date of death from any cause, assessed up to 36 months.
Number of Participants With Treatment-Emergent Adverse Events as Assessed by NCI-CTCAE v5.0
Time Frame: From first dose through 90 days after last dose, assessed up to approximately 36 months.
Adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity will be graded on a scale of 1 to 5, where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, and 5 = Death. The number of participants with treatment-emergent adverse events (TEAEs) of any grade will be reported.
From first dose through 90 days after last dose, assessed up to approximately 36 months.
Change from Baseline in Global Health Status/Quality of Life Score Assessed by EORTC QLQ-C30
Time Frame: Assessed at baseline (pre-dose), every 8 weeks during treatment (±7 days), at end of treatment (within 30 days after the last dose), at safety follow-up (Day 90 ±7 days after the last dose).

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a 30-item questionnaire used to assess the quality of life of cancer patients. The Global Health Status/Quality of Life (GHS/QoL) scale is derived from 2 specific items within the questionnaire (questions 29 and 30).

Scoring: The raw score is transformed to a linear scale ranging from 0 to 100. Interpretation: A higher score indicates a higher ("better") quality of life, while a lower score indicates a lower quality of life.
Assessed at baseline (pre-dose), every 8 weeks during treatment (±7 days), at end of treatment (within 30 days after the last dose), at safety follow-up (Day 90 ±7 days after the last dose).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital with Nanjing Medical University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Zhejiang Cancer Hospital
RenJi Hospital
The First Hospital of Jilin University
The Affiliated Hospital of Xuzhou Medical University
Anhui Provincial Hospital
Shanghai Minhang Central Hospital
Huai'an First People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 6, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NJMU-BC09

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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