A Multicenter, Single-Arm, Phase II Exploratory Study of Eribulin in Combination With Anlotinib for HER2-Negative Recurrent/Metastatic Breast Cancer Previously Treated With Antibody-Drug Conjugates (MBC-EA)

A Multicenter, Single-Arm, Phase II Exploratory Study of Eribulin in Combination With Anlotinib for HER2-Negative Recurrent/Metastatic Breast Cancer Previously Treated With Antibody-Drug Conjugates（MBC-EA-II-01）

This study is looking at a new combination of two drugs-eribulin and anlotinib-for patients with HER2-negative advanced breast cancer. Participants in this study have already tried other treatments like T-DXd or SG, but their cancer has gotten worse, and there are currently no standard treatment options left for them. Researchers believe that using these two drugs together may work better than using either one alone based on how they target cancer cells. The goal is to offer a new choice and help improve survival for these patients.

Study Overview

• Status: Recruiting
• Conditions: HER 2 Negative Breast Cancer
• Intervention / Treatment: Drug: Eribulin in Combination with Anlotinib

Detailed Description

This is an exploratory study designed to evaluate the efficacy of eribulin in combination with anlotinib in patients with HER2-negative recurrent or metastatic breast cancer who have experienced treatment failure with antibody-drug conjugates (ADCs). The study aims to assess the efficacy and safety of eribulin combined with anlotinib in the treatment of patients with recurrent or metastatic HER2-low breast cancer, and to provide clinical evidence supporting this novel combination regimen.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Meiting Chen, Doctor; Phone Number: 02087341812; Email: chenmt@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-Sen University Cancer Center
    • Contact: Meiting Chen, Doctor; Phone Number: 02087341812; Email: chenmt@sysucc.org.cn
    • Sub-Investigator: Meiting Chen, Doctor
    • Principal Investigator: Jiajia Huang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged ≥ 18 years with pathologically confirmed metastatic or locally advanced unresectable breast cancer.
2. HER2-negative status, defined as immunohistochemistry (IHC) 0 or 1+, or IHC 2+ with negative HER2 gene amplification by fluorescence in situ hybridization (FISH). If multiple specimens have been tested, the most recent test result will be used for determination.
3. Prior treatment with anthracycline- or taxane-containing chemotherapy, including in the neoadjuvant or adjuvant setting.
4. Intolerance or disease progression following prior treatment with an antibody-drug conjugate (ADC), without the initiation of a new treatment regimen after ADC therapy.
5. Received no more than 4 prior lines (including 4 lines) of chemotherapy.
6. At least one measurable lesion per RECIST v1.1.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
8. Life expectancy ≥ 12 weeks.

9. Adequate major organ function as defined by the following criteria:

   Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 75 × 10⁹/L, hemoglobin (Hb) ≥ 85 g/L (without transfusion or blood product support, or use of G-CSF or other hematopoietic growth factors within 14 days prior to screening).

   Biochemistry: Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN (or < 5 × ULN in patients with liver metastases); blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1 × ULN, or calculated creatinine clearance ≥ 50 mL/min (using the Cockcroft-Gault formula).

10. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must agree to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment. Women not of childbearing potential (i.e., surgically sterile or postmenopausal for at least 1 year) are eligible without requiring contraception.
11. Willing and able to provide written informed consent, with good compliance and willingness to complete scheduled follow-up.

Exclusion Criteria:

1. Untreated active brain metastases. Patients with asymptomatic central nervous system (CNS) metastases or those with stable brain metastases following radiotherapy are eligible.
2. Known spinal cord compression or active CNS metastases that have not been treated with surgery or radiotherapy, except for patients who have been stable for at least 1 month after treatment and have discontinued corticosteroids for > 2 weeks.
3. HER2-positive status, defined as immunohistochemistry (IHC) 3+, or IHC 2+ with positive HER2 gene amplification by fluorescence in situ hybridization (FISH). Patients with a prior HER2-positive status but who are HER2-negative per the most recent pathology test are eligible.
4. History of clinically significant cardiovascular, hepatic, respiratory, renal, hematological, endocrine, or neuropsychiatric diseases.
5. Acute or chronic active hepatitis B (defined as hepatitis B surface antigen [HBsAg] positive and/or hepatitis B core antibody [HBcAb] positive with hepatitis B virus [HBV] DNA copy number ≥ 1 × 10³ copies/mL or ≥ 200 IU/mL) or acute or chronic active hepatitis C (hepatitis C virus [HCV] antibody positive). Patients with positive HCV antibody but negative HCV RNA are eligible.
6. Receipt of anti-tumor monoclonal antibody therapy within 4 weeks prior to study initiation, or prior treatment with other anti-tumor therapies with unresolved adverse events/reactions.
7. Known inherited or acquired bleeding tendencies (e.g., hemophilia, coagulation disorders, etc.).
8. History or evidence of any disease, condition, treatment, or laboratory abnormality that may interfere with the study results or preclude the patient's full participation in the study, or any other condition deemed unsuitable for enrollment by the investigator.
9. Any severe underlying disease, comorbidity, or active infection.
10. Concurrent receipt of other anti-tumor therapy.
11. History of epilepsy or conditions predisposing to seizure.
12. Pregnant or breastfeeding women.
13. Poor compliance or inability to complete scheduled follow-up.
14. Known hypersensitivity to the study drugs.
15. Diagnosis of another malignancy within 3 years, except for the following: surgically resected non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, locally curative prostate cancer, surgically resected ductal carcinoma in situ, or malignancies diagnosed > 2 years prior to enrollment with no evidence of disease and no treatment within ≤ 2 years before randomization.
16. Any other condition that, in the investigator's judgment, may affect the conduct of the study or the interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TNBC and HR positive cohorts

Drug: Eribulin in Combination with Anlotinib; Participants will receive eribulin mesylate administered as a 1-hour intravenous infusion at a dose of 1.4 mg/m² on Days 1 and 8 of each 21-day cycle. Anlotinib will be administered orally at a dose of 8 mg once daily on Days 1 through 14 of each 21-day cycle, followed by a 7-day rest period. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival (PFS) is defined as the time from the first dose of study treatment to the first documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first. For patients who have not experienced disease progression or death at the time of analysis, PFS will be censored at the date of the last adequate tumor assessment. If no post-baseline tumor assessment is available, PFS will be censored at the date of first dose. Disease progression is determined by investigator assessment based on imaging evaluations (e.g., CT, MRI) performed at baseline and at scheduled time points throughout the study. Unit of Measure: Months	From date of first dose until the date of first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) is defined as the time from the first dose of study treatment to death from any cause. For patients who are alive at the time of analysis, OS will be censored at the last known date the patient was known to be alive. If no post-baseline follow-up information is available, OS will be censored at the date of first dose. Survival status is collected through scheduled follow-up visits and/or via telephone contact at the end of the study. Unit of Measure: Months	From date of first dose until death from any cause, assessed up to 36 months
Safety	Safety and tolerability will be assessed by evaluating the incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs). AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Unit of Measure: Number of participants	From date of informed consent through 30 days after last dose of study treatment
Quality of Life (QoL)	Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the breast cancer-specific module. Unit of Measure: Score on a scale	From baseline to end of study follow-up, assessed up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of PIK3CA, ESR1, and GATA3 (PEG) Gene Mutations	The presence or absence of mutations in the PIK3CA, ESR1, and GATA3 genes (PEG gene panel) will be assessed using next-generation sequencing (NGS) performed on tumor tissue or circulating tumor DNA (ctDNA) collected at baseline. Unit of Measure: Mutant-type category (Mutant vs. Wild-type)	Baseline
Change in Metabolite Concentrations	Blood samples will be collected at baseline and during study treatment. Metabolomic profiling will be performed using liquid chromatography-mass spectrometry (LC-MS) to identify and quantify the concentration of specific metabolites. Unit of Measure: Concentration (μM or relative abundance)	Baseline and during study treatment

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2035

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Eribulin; Anlotinib; HER2-Negative Recurrent/Metastatic Breast Cancer; Previously Treated with Antibody-Drug Conjugates
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; anlotinib; eribulin
• Other Study ID Numbers: MBC-EA-II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No