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

NCT07333937 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: XJYY-KY-20252554
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Brest Cancer

Keywords

Neratinib; Fulvestrant; Eribulin; HR+/HER2+ Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  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 Outcomes (5)

• progression free survival

  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

  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

  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

  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

  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.

Study Arms (1)

Neratinib Combined with Fulvestrant and Eribulin

EXPERIMENTAL

Neratinib Combined with Fulvestrant and Eribulin after Trastuzumab Deruxtecan Resistance

Drug: Neratinib Combined with Fulvestrant and Eribulin

Interventions

Neratinib Combined with Fulvestrant and Eribulin DRUG

neratinib combined with fulvestrant and eribulin in the treatment of HR+/HER2+ advanced breast cancer after trastuzumab deruxtecan resistance

Neratinib Combined with Fulvestrant and Eribulin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xijing Hospital: lead

MeSH Terms

Interventions

Fulvestrant; eribulin

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Ethics Committee of the First Affiliated Hospital of Air Force

CONTACT

029-84771794; EC84771794@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: January 12, 2026
• Study Start: December 20, 2025
• Primary Completion (Estimated): November 20, 2027
• Study Completion (Estimated): November 20, 2028
• Last Updated: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share