Eribulin plus anlotinib for HER2‑negative recurrent or metastatic breast cancer after ADCs

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 trial tests whether combining eribulin and anlotinib helps people with HER2‑negative recurrent or metastatic breast cancer whose disease progressed after antibody‑drug conjugates.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, anlotinib
• Locations: 1 site (Guangzhou)
• Trial ID: NCT07520760 on ClinicalTrials.gov

What this trial studies

This is a multicenter, single‑arm Phase II exploratory trial testing eribulin, a microtubule inhibitor, together with anlotinib, an oral anti‑angiogenic tyrosine kinase inhibitor, in patients with HER2‑negative recurrent or metastatic breast cancer. Eligible participants have progressed on or are intolerant to prior antibody‑drug conjugate therapy and must have measurable disease by RECIST v1.1, ECOG 0–1, and no more than four prior lines of chemotherapy. The regimen will be given according to protocol dosing with regular imaging and safety monitoring to document tumor responses, adverse events, and survival outcomes. The goal is to generate early evidence on activity and tolerability of this combination in a treatment‑resistant population.

Who should consider this trial

Good fit: Adult women (≥18 years) with pathologically confirmed HER2‑negative recurrent or metastatic breast cancer, measurable disease, prior progression or intolerance to an antibody‑drug conjugate, ECOG performance status 0–1, adequate organ function, and no more than four prior lines of chemotherapy are the ideal candidates.

Not a fit: Patients who are HER2‑positive, have ECOG >1, poor organ function, have received more than four prior chemotherapy lines, or who have effective alternative treatments available are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could provide a new treatment option that prolongs disease control and potentially improves survival for patients who have exhausted ADCs.

How similar studies have performed: Eribulin has shown single‑agent activity in metastatic breast cancer and anti‑angiogenic TKIs have shown signals in combination with chemotherapy in other cancers, but this specific eribulin–anlotinib combination after ADC failure is novel and not yet proven.

Eligibility criteria

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.

Where this trial is running

Guangzhou

• Sun yat-Sen University Cancer Center — Guangzhou, China (RECRUITING)

Study contacts

• Study coordinator: Meiting Chen, Doctor

Conditions: HER 2 Negative Breast Cancer, HER2-Negative Recurrent/Metastatic Breast Cancer, Previously Treated with Antibody-Drug Conjugates, Eribulin, Anlotinib