Neratinib Combined With Fulvestrant and Eribulin in the Treatment ofHR+/HER2+ Advanced Breast Cancer (NETHER)

December 31, 2025 updated by: Xijing Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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.

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 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.
35

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.
  • Name: Ethics Committee of the First Affiliated Hospital of Air Force
  • Phone Number: 029-84771794
  • Email: EC84771794@163.com

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:

  • 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);
  • 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.

Exclusion Criteria:

  • 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;
  • 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.

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: Neratinib Combined with Fulvestrant and Eribulin
Neratinib Combined with Fulvestrant and Eribulin after Trastuzumab Deruxtecan Resistance
Drug: Neratinib Combined with Fulvestrant and Eribulin
neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance

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
Measure Description
Time Frame
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
From treatment initiation to disease progression, intolerable toxicity, or study completion, whichever occurs first，assessed up to 10 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
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
the length of time from a patient's enrollment to the first occurrence of either "disease progression (PD)" or "death from any cause".
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
the length of time from a patient's enrollment to death from any cause
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
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
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.
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.

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.
Xijing 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 (Estimated)

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.
December 20, 2025

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.
November 20, 2027

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.
November 20, 2028

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).
December 14, 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.
December 31, 2025

First Posted (Estimated)

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.
January 12, 2026

Study Record Updates

Last Update Posted (Estimated)

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.
January 12, 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.
December 31, 2025

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.
December 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.
  • XJYY-KY-20252554

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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