HER2-low Breast CancerPhase 2NCT07446452
Disitamab Vedotin Plus Bevacizumab in HER2-Low Metastatic Breast Cancer After T-DXd Failure: A Phase II Study
A Phase 2 study testing Disitamab Vedotin (RC48) and Bevacizumab in people with HER2-low Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- HER2-low Breast Cancer
- What is being tested?
- Disitamab Vedotin (RC48) and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2024to 1 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu
Li Wei, Ph.D, 025-68307102, liwei1218@njmu.edu.cn
About this study
Official title: 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.
- Conditions
- HER2-low Breast Cancer
- Being tested
- Disitamab Vedotin (RC48), Bevacizumab
- Keywords
- Disitamab Vedotin (RC48), Bevacizumab, Trastuzumab deruxtecan failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disitamab Vedotin (RC48)Drug
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.
BevacizumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Disitamab Vedotin + Bevacizumab | Experimental | 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. Receives: Drug: Disitamab Vedotin (RC48); Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Measured: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
Secondary outcomes (6)
Progression-Free Survival (PFS)
Measured: 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)
Measured: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
Duration of Response (DOR)
Measured: From first documented tumor response (CR or PR) until disease progression or death, whichever occurs first, assessed up to 24 months.
Overall Survival (OS)
Measured: 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
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.
Measured: 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
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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2026
- Study start1 Jan 2024
- Primary completion6 Dec 2026 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-low Breast CancerStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- RenJi Hospital, Anhui Provincial Hospital, The Affiliated Hospital of Xuzhou Medical University, The First Hospital of Jilin University, Shanghai Minhang Central Hospital, Zhejiang Cancer Hospital, Huai'an First People's Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07446452
- Sponsor's protocol ID
- NJMU-BC09
- Status last verified
- Nov 2025
- First submitted
- 24 Nov 2025
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07446452
- Acronym / sponsor ID
- NJMU-BC09
- Conditions
- HER2-low Breast Cancer
- Keywords
- Disitamab Vedotin (RC48), Bevacizumab, Trastuzumab deruxtecan failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- RenJi Hospital, Anhui Provincial Hospital, The Affiliated Hospital of Xuzhou Medical University, The First Hospital of Jilin University, Shanghai Minhang Central Hospital, Zhejiang Cancer Hospital, Huai'an First People's Hospital
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 6 Dec 2026 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 3 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Disitamab Vedotin + Bevacizumab | Experimental | Drug: Disitamab Vedotin (RC48), Drug: BevacizumabParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Disitamab Vedotin + Bevacizumab |
| BevacizumabA 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. | Drug | Disitamab Vedotin + Bevacizumab |
Primary outcome
Objective Response Rate (ORR)
Time frame: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.
6 secondary outcomes
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.
Disease Control Rate (DCR)
Time frame: 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.
Overall Survival (OS)
Time frame: 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.
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Individual participant dataSharing planned: Yes
Related trials for HER2-low Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingPhase 2
Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Breast Neoplasms, Breast Cancer
RecruitingObservational study
Negative/Low Hormone Receptor And/or HER2 POsitive Lobular Invasive Breast Carcinoma - A Real-World International Cohort Study
Lobular Breast Carcinoma
Active, not recruitingPhase 3
A Study of Elacestrant Versus Standard Endocrine Therapy in Women and Men With ER+,HER2-, Early Breast Cancer With High Risk of Recurrence
Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Disitamab Vedotin (RC48) and Bevacizumab in people with HER2-low Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Li, Ph.D (025-68307102, liwei1218@njmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From first dose until disease progression or death, whichever occurs first, assessed up to 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.