HER2-positive Breast CancerPhase 2/3BRIGHTNCT07366840
RC48 Combined With Chemotherapy in HER2-Positive Advanced Breast Cancer Patients With Prior TOP1i-ADC Failure
A Phase 2/3 study testing Disitamab Vedotin, Gemcitabine and Capecitabine in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Fudan University.
Trial summary
The purpose of this study is to assess the safety and efficacy of RC48 (a HER2 antibody drug conjugate with MMAE payload) in combination with gemcitabine or capecitabine (with or without trastuzumab/inetetamab), for treatment of patients with HER2-positive advanced breast cancer (ABC) who have developed disease… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER2-positive Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Disitamab Vedotin, Gemcitabine and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 268 participants
- Where
- No sites listed yet
- Study dates
- 16 Jan 2026to 16 Jan 2029
- Phase
- Phase 2/3
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subjects aged ≥ 18 years.
- Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with positive FISH) advanced breast cancer.
- Disease progression on or intolerance to prior treatment with a topoisomerase I inhibitor-conjugated antibody-drug conjugate (TOP1i-ADC).
- ≤ 3 lines of systemic therapy received in the recurrent or metastatic setting. Prior exposure to only one ADC agent.
- At least one extracranial measurable lesion according to RECIST v1.1 criteria.
- ECOG Performance Status (PS) of 0 or 1.
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- Adequate function of major organs, meeting the following criteria:Hematological criteria:Hemoglobin (HB) ≥ 90 g/L (no blood transfusion within 14 days prior);Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L;Platelet count (PLT) ≥ 75 × 10⁹/L.Biochemical criteria:Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN; for subjects with liver metastases, ALT and AST ≤ 5 × ULN;Serum Creatinine (Cr) ≤ 1 × ULN, and calculated Creatinine Clearance Rate (Ccr) > 50 mL/min (using the Cockcroft-Gault formula).
- Expected survival ≥ 3 months.
- No prior radiotherapy, chemotherapy, endocrine therapy, molecular targeted therapy or surgery within 3 weeks prior to the start of the study; complete recovery from acute toxicities of previous treatments (if surgery was performed, surgical wounds must be fully healed); no peripheral neuropathy or peripheral neurotoxicity of Grade 1 at most.
- Female subjects with childbearing potential must use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last administration of the study drug.
- Voluntary participation in the study, provision of written informed consent, and good compliance with study procedures and follow-up schedules.
Who cannot join
- Unstable brain metastases, leptomeningeal metastases, or untreated brain metastases (excluding subjects with treated and stable brain metastases who have been asymptomatic for ≥ 4 weeks).
- A history of arterial or venous thromboembolic events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 3 years prior to the start of study treatment.
- Uncontrolled systemic diseases, including diabetes mellitus, hypertension, pulmonary fibrosis, acute lung disease, liver cirrhosis, etc.
- Current active infection requiring systemic treatment.
- Failure to recover from toxicities of prior anti-tumor therapy to CTCAE v5.0 Grade 0 or 1 (except for alopecia, hyperpigmentation, or other conditions deemed by the investigator not to increase the risk of study drug administration).
- A history of clinically significant or uncontrolled cardiac diseases, including severe ventricular arrhythmia, congestive heart failure, angina pectoris, or myocardial infarction within 6 months prior.
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- Known immediate or delayed hypersensitivity to RC48 or any of its components.
- Pregnant or lactating women.
- A history of other malignancies within 3 years prior (except for bilateral breast cancer with HER2 positivity in both lesions, cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma with favorable prognosis, or carcinoma in situ of the lung or minimally invasive adenocarcinoma with favorable prognosis).
- Any other conditions that, in the investigator's judgment, make the subject unsuitable for participation in the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 3, Randomized Advanced Breast Cancer Study Investigating RC48 Combined With Chemotherapy Versus Guideline-recommended Trastuzumab/Inetetamab Plus Chemotherapy in HER2-Positive Patients With Prior TOP1i-ADC Failure
The purpose of this study is to assess the safety and efficacy of RC48 (a HER2 antibody drug conjugate with MMAE payload) in combination with gemcitabine or capecitabine (with or without trastuzumab/inetetamab), for treatment of patients with HER2-positive advanced breast cancer (ABC) who have developed disease progression or intolerance to prior therapy with a topoisomerase I inhibitor antibody-drug conjugate (TOP1i-ADC).
Read the detailed description
This is a randomized, open-label, parallel-controlled, multi-centered, phase 3 clinical study enrolling patients with HER2-positive ABC who have experienced disease progression or intolerance to prior TOP1i-ADC treatment, with ≤ 3 lines of systemic therapy received in the recurrent/metastatic setting. The study consists of two main parts: Part 1: Run-in Phase and Part 2: Randomized Controlled Trial.
Part 1: Run-in Phase The primary objective of the Run-in Phase is to preliminarily verify whether the addition of trastuzumab or inetetamab to the combination regimen of RC48 plus chemotherapy can enhance the anti-tumor efficacy and whether it is associated with any specific toxicities. This phase comprises two regimens, and 30 patients will be randomized 1:1 to receive treatment with either of the two regimens: RC48 plus Gemcitabine or Capecitabine; RC48 plus Gemcitabine or Capecitabine, plus Trastuzumab or Inetetamab.
. Part 2: Randomized Controlled Trial The primary objective of this part is to assess the anti-tumor activity and safety of the optimal regimen identified in Part 1 in patients with HER2-positive ABC who have failed prior TOP1i-ADC treatment. Eligible patients will be stratified and randomized 1:1 to either the experimental group or the control group. 238 patients are expected to be enrolled in Part 2.
Experimental group: RC48 plus Gemcitabine or Capecitabine ± Trastuzumab or Inetetamab.
Control group: Trastuzumab or Inetetamab plus Gemcitabine or Capecitabine.
- Being tested
- Disitamab Vedotin, Gemcitabine, Capecitabine, Trastuzumab, Inetetamab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disitamab VedotinDrug
Also called RC48
2.0mg/kg every two weeks
GemcitabineDrug
1000mg/m2 on days 1 and 8 every three weeks
CapecitabineDrug
1000 mg/m2 twice daily on days 1 to14 every three weeks
TrastuzumabDrug
6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg
InetetamabDrug
6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Disitamab Vedotin plus chemo | Experimental | Participants received Disitamab Vedotin (RC48), 2.0mg/kg intravenously on day 1 of two-week cycle, plus chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000 mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity. Receives: Drug: Disitamab Vedotin; Drug: Gemcitabine; Drug: Capecitabine; Drug: Inetetamab |
| Trastuzumab plus chemo | Experimental | Participants received chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity. Receives: Drug: Gemcitabine; Drug: Capecitabine; Drug: Trastuzumab; Drug: Inetetamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median progression free survival (by investigator)
Progression-Free Survival (PFS), analyzed using the Kaplan-Meier method, is defined as the time from randomization to the first occurrence of disease progression or death, whichever comes first. For subjects without evidence of disease progression or death at the time of analysis, data will be censored at the date of their last tumor assessment.
Measured: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Secondary outcomes (5)
Objective Response Rate (by investigator)
Objective response rate (ORR), defined as best overall response of either complete or partial response based on RECIST 1.1 criteria, will be assessed among participants who have measurable disease at screening and start protocol therapy.
Measured: Baseline at screening and the time of the identification of disease progression, assessed up to 36 months.
Median overall survival (by investigator)
Overall Survival (OS), analyzed using the Kaplan-Meier method, is defined as the time from randomization to death from any cause. For participants who remain alive at the time of analysis, data will be censored at the date of last contact or informed consent withdrawal.
Measured: The observation period for this endpoint will be terminated upon death or if disease progression occurs after 1 year of follow-up.
Duration of response (by investigator)
Duration of Overall Response (DOR) is defined as the time from the first documentation of meeting the criteria for Complete Response (CR) or Partial Response (PR) to the first date of objectively confirmed disease recurrence, progression, or death from any cause. For disease progression, the reference shall be the smallest tumor measurements recorded since the initiation of treatment.
Measured: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Disease control rate (by investigator)
Disease control rate (DCR) is defined as the percentage of participants with CR, PR, or stable disease (SD) by investigator per RECIST v1.1.
Measured: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Adverse events
The number of participants who experienced an adverse event (AE) based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms, whether or not considered related to the investigational medicines.
Measured: The observation period for this endpoint is up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start16 Jan 2026 (estimated)
- Primary completion16 Jan 2028 (estimated)
- Study completion16 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 268 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Zhang,MD, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07366840
- Sponsor's protocol ID
- 2510331-7
- Acronym
- BRIGHT
- Status last verified
- Jan 2026
- First submitted
- 14 Jan 2026
- Last updated
- 26 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized Advanced Breast Cancer Study Investigating RC48 Combined With Chemotherapy Versus Guideline-recommended Trastuzumab/Inetetamab Plus Chemotherapy in HER2-Positive Patients With Prior TOP1i-ADC Failure
- ClinicalTrials.gov ID
- NCT07366840
- Acronym / sponsor ID
- BRIGHT / 2510331-7
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 268 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 16 Jan 2026 (estimated)
- Primary completion
- 16 Jan 2028 (estimated)
- Study completion
- 16 Jan 2029 (estimated)
- First posted
- 26 Jan 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.
The purpose of this study is to assess the safety and efficacy of RC48 (a HER2 antibody drug conjugate with MMAE payload) in combination with gemcitabine or capecitabine (with or without trastuzumab/inetetamab), for treatment of patients with HER2-positive advanced breast cancer (ABC) who have developed disease progression or intolerance to prior therapy with a topoisomerase I inhibitor antibody-drug conjugate (TOP1i-ADC).
Detailed description
This is a randomized, open-label, parallel-controlled, multi-centered, phase 3 clinical study enrolling patients with HER2-positive ABC who have experienced disease progression or intolerance to prior TOP1i-ADC treatment, with ≤ 3 lines of systemic therapy received in the recurrent/metastatic setting. The study consists of two main parts: Part 1: Run-in Phase and Part 2: Randomized Controlled Trial.
Part 1: Run-in Phase The primary objective of the Run-in Phase is to preliminarily verify whether the addition of trastuzumab or inetetamab to the combination regimen of RC48 plus chemotherapy can enhance the anti-tumor efficacy and whether it is associated with any specific toxicities. This phase comprises two regimens, and 30 patients will be randomized 1:1 to receive treatment with either of the two regimens: RC48 plus Gemcitabine or Capecitabine; RC48 plus Gemcitabine or Capecitabine, plus Trastuzumab or Inetetamab.
. Part 2: Randomized Controlled Trial The primary objective of this part is to assess the anti-tumor activity and safety of the optimal regimen identified in Part 1 in patients with HER2-positive ABC who have failed prior TOP1i-ADC treatment. Eligible patients will be stratified and randomized 1:1 to either the experimental group or the control group. 238 patients are expected to be enrolled in Part 2.
Experimental group: RC48 plus Gemcitabine or Capecitabine ± Trastuzumab or Inetetamab.
Control group: Trastuzumab or Inetetamab plus Gemcitabine or Capecitabine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Disitamab Vedotin plus chemo | Experimental | Drug: Disitamab Vedotin, Drug: Gemcitabine, Drug: Capecitabine, Drug: InetetamabParticipants received Disitamab Vedotin (RC48), 2.0mg/kg intravenously on day 1 of two-week cycle, plus chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000 mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity. |
| Trastuzumab plus chemo | Experimental | Drug: Gemcitabine, Drug: Capecitabine, Drug: Trastuzumab, Drug: InetetamabParticipants received chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Female subjects aged ≥ 18 years.
- Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with positive FISH) advanced breast cancer.
- Disease progression on or intolerance to prior treatment with a topoisomerase I inhibitor-conjugated antibody-drug conjugate (TOP1i-ADC).
- ≤ 3 lines of systemic therapy received in the recurrent or metastatic setting. Prior exposure to only one ADC agent.
- At least one extracranial measurable lesion according to RECIST v1.1 criteria.
Key exclusion criteria (10 listed)
- Unstable brain metastases, leptomeningeal metastases, or untreated brain metastases (excluding subjects with treated and stable brain metastases who have been asymptomatic for ≥ 4 weeks).
- A history of arterial or venous thromboembolic events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 3 years prior to the start of study treatment.
- Uncontrolled systemic diseases, including diabetes mellitus, hypertension, pulmonary fibrosis, acute lung disease, liver cirrhosis, etc.
- Current active infection requiring systemic treatment.
- Failure to recover from toxicities of prior anti-tumor therapy to CTCAE v5.0 Grade 0 or 1 (except for alopecia, hyperpigmentation, or other conditions deemed by the investigator not to increase the risk of study drug administration).
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 VedotinAlso: RC482.0mg/kg every two weeks | Drug | Disitamab Vedotin plus chemo |
| Gemcitabine1000mg/m2 on days 1 and 8 every three weeks | Drug | Disitamab Vedotin plus chemo, Trastuzumab plus chemo |
| Capecitabine1000 mg/m2 twice daily on days 1 to14 every three weeks | Drug | Disitamab Vedotin plus chemo, Trastuzumab plus chemo |
| Trastuzumab6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg | Drug | Trastuzumab plus chemo |
| Inetetamab6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg | Drug | Disitamab Vedotin plus chemo, Trastuzumab plus chemo |
Primary outcome
Median progression free survival (by investigator)
Time frame: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Progression-Free Survival (PFS), analyzed using the Kaplan-Meier method, is defined as the time from randomization to the first occurrence of disease progression or death, whichever comes first. For subjects without evidence of disease progression or death at the time of analysis, data will be censored at the date of their last tumor assessment.
5 secondary outcomes
Objective Response Rate (by investigator)
Time frame: Baseline at screening and the time of the identification of disease progression, assessed up to 36 months.
Median overall survival (by investigator)
Time frame: The observation period for this endpoint will be terminated upon death or if disease progression occurs after 1 year of follow-up.
Duration of response (by investigator)
Time frame: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Disease control rate (by investigator)
Time frame: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.
Adverse events
Time frame: The observation period for this endpoint is up to 36 months.
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 26 Jan 2026.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Disitamab Vedotin, Gemcitabine and Capecitabine in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Fudan University.
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 11 inclusion and 10 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: opening soon, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Jian Zhang, MD (+8664175590 ext. 85000, syner2000@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median progression free survival (by investigator) (time frame: The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.). 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 26 Jan 2026.