Brest CancerPhase 2NETHERNCT07333937
Neratinib Combined With Fulvestrant and Eribulin in the Treatment ofHR+/HER2+ Advanced Breast Cancer
A Phase 2 study testing Neratinib Combined with Fulvestrant and Eribulin in people with Brest Cancer, run by Xijing Hospital.
Trial summary
This study aims to explore the efficacy and safety of neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Brest Cancer
- What is being tested?
- Neratinib Combined with Fulvestrant and Eribulin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- 20 Dec 2025to 20 Nov 2028
- 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
- Female patients aged ≥18 years and ≤75 years;
- ECOG performance status of 0-2;
- Histologically confirmed HR-positive/HER2-positive advanced breast cancer:
- Definition of HER2 positivity: IHC 3+ or IHC 2+/ISH positive prior to T-DXd treatment;
- Definition of HR positivity: ER or PR ≥1%;
- Refractory to prior treatment containing T-DXd (definition of resistance: a. Definite disease progression per RECIST v1.1 criteria; b. Intolerance to T-DXd treatment);
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- Prior exposure to anthracyclines and taxanes (including use in the adjuvant/neoadjuvant setting);
- Presence of at least one measurable lesion (per RECIST v1.1 criteria);
- Estimated survival time ≥3 months;
- Adequate function of major organs, meeting the following requirements (no blood transfusion, no use of leukocyte- or platelet-stimulating agents within 2 weeks prior to screening);
- For premenopausal or non-surgically sterilized female patients: Agreement to abstain from sexual activity or use effective contraceptive methods during treatment and for at least 7 months after the last dose of study treatment;
- Voluntary participation in the study, signing of the informed consent form, good compliance, and willingness to cooperate with follow-up.
Who cannot join
- Severe allergic reactions to neratinib, eribulin, fulvestrant, or any of their excipients;
- Prior treatment with neratinib, other small-molecule anti-HER2 TKIs, or eribulin;
- Patients with inflammatory breast cancer;
- A history of other malignant tumors within the past 5 years or concurrent malignant tumors (including cured malignant tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma);
- Concurrent receipt of anti-tumor therapies in other clinical trials, including endocrine therapy, bisphosphonate therapy, or immunotherapy;
- Receipt of major surgical procedures unrelated to breast cancer within 4 weeks prior to enrollment, or failure to fully recover from such surgical procedures;
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- Severe cardiac diseases or disorders, including but not limited to: --Documented history of heart failure or systolic dysfunction (LVEF < 50%); --High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or high-grade atrioventricular block (i.e., Mobitz II second-degree atrioventricular block or third-degree atrioventricular block);
- Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg);
- Inability to swallow, intestinal obstruction, or other factors affecting drug administration and absorption;
- Known history of allergies to any components of the study drugs; history of immunodeficiency (including positive HIV test results), other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
- Pregnant or lactating female patients; female patients of childbearing potential with a positive baseline pregnancy test; or fertile patients unwilling to use effective contraceptive methods throughout the trial and for 7 months after the last dose of study treatment;
- Severe comorbid diseases or other concurrent conditions that may interfere with the planned treatment, or any other circumstances deemed by the investigator to make the patient 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.
Ethics Committee of the First Affiliated Hospital of Air Force contact
About this study
Official title: Neratinib Combined With Fulvestrant and Eribulin in the Treatment ofHR+/HER2+ Advanced Breast Cancer After Trastuzumab Deruxtecan Resistance:A Single-Arm, Multicenter, Exploratory Clinical Study
This study aims to explore the efficacy and safety of neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance. The treatment regimen of neratinib + fulvestrant + eribulin in this study is expected to provide a new and effective therapeutic strategy for patients with triple-positive breast cancer who develop resistance to trastuzumab deruxtecan, and offer novel therapeutic insights for advanced triple-positive breast cancer.
Read the detailed description
This study is a single-arm, exploratory clinical trial. Eligible patients with recurrent or metastatic breast cancer will be screened and enrolled after signing the informed consent form, and will receive neratinib combined with fulvestrant and eribulin until disease progression or intolerable toxicity occurs. During the treatment period, clinical tumor imaging assessments will be performed every 6 weeks (2 cycles) in accordance with RECIST v1.1; safety assessments will be conducted using NCI-CTCAE 5.0, and adverse events will be recorded throughout the study and within 30 days after the end of treatment (the recording period for serious adverse events or adverse events related to the drugs involved in this trial will be extended to 90 days after the end of treatment).
- Conditions
- Brest Cancer
- Being tested
- Neratinib Combined with Fulvestrant and Eribulin
- Keywords
- Neratinib, Fulvestrant, Eribulin, HR+/HER2+ Advanced Breast Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neratinib Combined with Fulvestrant and EribulinDrug
neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance
| Study group | Role | What they receive |
|---|---|---|
| Neratinib Combined with Fulvestrant and Eribulin | Experimental | Neratinib Combined with Fulvestrant and Eribulin after Trastuzumab Deruxtecan Resistance Receives: Drug: Neratinib Combined with Fulvestrant and Eribulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate(ORR)
The proportion of patients whose tumor lesions achieve "Partial Response (PR)" or "Complete Response (CR)" after treatment
Measured: From treatment initiation to disease progression, intolerable toxicity, or study completion, whichever occurs first，assessed up to 10 months
Secondary outcomes (5)
progression free survival
the length of time from a patient's enrollment to the first occurrence of either "disease progression (PD)" or "death from any cause".
Measured: From first treatment initiation to the first occurrence of disease progression (per RECIST v1.1) or death from any cause, or study completion (whichever occurs first)，assessed up to 60 months
overall survival
the length of time from a patient's enrollment to death from any cause
Measured: From first treatment initiation to death from any cause or study completion, whichever occurs first, with a minimum follow-up of 12 months for surviving patients，assessed up to 100 months
Disease control rate
Measured: From first treatment initiation to disease progression, intolerable toxicity, or study completion (whichever occurs first), with disease control status confirmed for ≥4 weeks per RECIST v1.1
duration of response
Measured: From the first confirmed Complete Response (CR) or Partial Response (PR) (per RECIST v1.1, maintained for ≥4 weeks) to the first documented disease progression (PD) or death from any cause, or study completion，assessed up to 10 months
adverse effects
Measured: From the first dose of study treatment (neratinib + fulvestrant + eribulin) to 30 days after the last dose of study treatment. For serious adverse events (SAEs), the follow-up and recording period is extended to 90 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 posted12 Jan 2026
- Study start20 Dec 2025 (estimated)
- Primary completion20 Nov 2027 (estimated)
- Study completion20 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brest CancerStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe 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
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07333937
- Sponsor's protocol ID
- XJYY-KY-20252554
- Acronym
- NETHER
- Status last verified
- Dec 2025
- First submitted
- 14 Dec 2025
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neratinib Combined With Fulvestrant and Eribulin in the Treatment ofHR+/HER2+ Advanced Breast Cancer After Trastuzumab Deruxtecan Resistance:A Single-Arm, Multicenter, Exploratory Clinical Study
- ClinicalTrials.gov ID
- NCT07333937
- Acronym / sponsor ID
- NETHER / XJYY-KY-20252554
- Conditions
- Brest Cancer
- Keywords
- Neratinib, Fulvestrant, Eribulin, HR+/HER2+ Advanced Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- 20 Dec 2025 (estimated)
- Primary completion
- 20 Nov 2027 (estimated)
- Study completion
- 20 Nov 2028 (estimated)
- First posted
- 12 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.
This study aims to explore the efficacy and safety of neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance. The treatment regimen of neratinib + fulvestrant + eribulin in this study is expected to provide a new and effective therapeutic strategy for patients with triple-positive breast cancer who develop resistance to trastuzumab deruxtecan, and offer novel therapeutic insights for advanced triple-positive breast cancer.
Detailed description
This study is a single-arm, exploratory clinical trial. Eligible patients with recurrent or metastatic breast cancer will be screened and enrolled after signing the informed consent form, and will receive neratinib combined with fulvestrant and eribulin until disease progression or intolerable toxicity occurs. During the treatment period, clinical tumor imaging assessments will be performed every 6 weeks (2 cycles) in accordance with RECIST v1.1; safety assessments will be conducted using NCI-CTCAE 5.0, and adverse events will be recorded throughout the study and within 30 days after the end of treatment (the recording period for serious adverse events or adverse events related to the drugs involved in this trial will be extended to 90 days after the end of treatment).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neratinib Combined with Fulvestrant and Eribulin | Experimental | Drug: Neratinib Combined with Fulvestrant and EribulinNeratinib Combined with Fulvestrant and Eribulin after Trastuzumab Deruxtecan Resistance |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Female patients aged ≥18 years and ≤75 years;
- ECOG performance status of 0-2;
- Histologically confirmed HR-positive/HER2-positive advanced breast cancer:
- Definition of HER2 positivity: IHC 3+ or IHC 2+/ISH positive prior to T-DXd treatment;
- Definition of HR positivity: ER or PR ≥1%;
Key exclusion criteria (12 listed)
- Severe allergic reactions to neratinib, eribulin, fulvestrant, or any of their excipients;
- Prior treatment with neratinib, other small-molecule anti-HER2 TKIs, or eribulin;
- Patients with inflammatory breast cancer;
- A history of other malignant tumors within the past 5 years or concurrent malignant tumors (including cured malignant tumors such as carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma);
- Concurrent receipt of anti-tumor therapies in other clinical trials, including endocrine therapy, bisphosphonate therapy, or immunotherapy;
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 |
|---|---|---|
| Neratinib Combined with Fulvestrant and Eribulinneratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance | Drug | Neratinib Combined with Fulvestrant and Eribulin |
Primary outcome
Objective response rate(ORR)
Time frame: From treatment initiation to disease progression, intolerable toxicity, or study completion, whichever occurs first，assessed up to 10 months
The proportion of patients whose tumor lesions achieve "Partial Response (PR)" or "Complete Response (CR)" after treatment
5 secondary outcomes
progression free survival
Time frame: From first treatment initiation to the first occurrence of disease progression (per RECIST v1.1) or death from any cause, or study completion (whichever occurs first)，assessed up to 60 months
overall survival
Time frame: From first treatment initiation to death from any cause or study completion, whichever occurs first, with a minimum follow-up of 12 months for surviving patients，assessed up to 100 months
Disease control rate
Time frame: From first treatment initiation to disease progression, intolerable toxicity, or study completion (whichever occurs first), with disease control status confirmed for ≥4 weeks per RECIST v1.1
duration of response
Time frame: From the first confirmed Complete Response (CR) or Partial Response (PR) (per RECIST v1.1, maintained for ≥4 weeks) to the first documented disease progression (PD) or death from any cause, or study completion，assessed up to 10 months
adverse effects
Time frame: From the first dose of study treatment (neratinib + fulvestrant + eribulin) to 30 days after the last dose of study treatment. For serious adverse events (SAEs), the follow-up and recording period is extended to 90 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 12 Jan 2026.
- Individual participant dataSharing planned: No
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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.
Ethics Committee of the First Affiliated Hospital of Air Force contact
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neratinib Combined with Fulvestrant and Eribulin in people with Brest Cancer, run by Xijing Hospital.
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 12 inclusion and 12 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 12 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 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 Ethics Committee of the First Affiliated Hospital of Air Force (029-84771794, EC84771794@163.com), 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 treatment initiation to disease progression, intolerable toxicity, or study completion, whichever occurs first，assessed up to 10 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 12 Jan 2026.