A Phase II Clinical Study Evaluating Entinostat With or Without Anlotinib + Fulvestrant for the Treatment of Hormone Receptor (HR) -Positive, Human Epidermal Growth Factor Receptor-2 (HER-2) -Negative Advanced Breast Cancer That Relapsed or Progressed After Endocrine Therapy

NCT07330544 | Recruiting Phase 2

• 1 other identifier: EAF-BC-IIT-001
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

• This study was an open, multicenter phase II clinical trial that enrolled 118 patients with HR+/HER2- with recurrent or progressive advanced breast cancer treated with CDK4/6 inhibitors;
• The study adopted the Simon phase 2 design, and all 20 eligible patients were treated with entinostat + fulvestrant; The study was terminated if no more than 2 patients achieved objective response and continued to enter Phase 2 if no more than 3 patients achieved objective response. In Phase 2, qualified patients were randomly assigned at a ratio of 1:1.5 to either the entestasta + fluvestrus group (Group 1) or the anlotinib + entestasta + fluvestrus group (Group 2), with 39 patients enrolled in group 1 and 59 patients enrolled in group 2; All patients were treated until the subjects' treatment would continue until the subjects experienced disease progression, intolerable toxicity, active withdrawal from treatment, or other conditions specified in the protocol, whichever occurred first.
• During the study period, efficacy evaluations will be conducted every 8 weeks in accordance with the Solid Tumor Efficacy Evaluation Criteria (RECIST) v1.1 until disease progression, the initiation of a new anti-tumor treatment by the subject, or the withdrawal of informed consent, whichever occurs first.
• Continuous safety evaluations will be conducted during the study treatment period. All subjects who have received at least one study treatment will be required to undergo end-of-treatment visits and safety follow-up visits within 7 days and 30±2 days after the last study treatment, respectively.
• The end of the study was defined as the occurrence of disease progression or the end of the study treatment in all subjects, or the early termination of the study for other reasons, whichever occurred first.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  To evaluate the objective response rate (ORR) of entinostat combined with fulvestrant in the treatment of HR+/HER2- advanced breast cancer that has recurred or progressed after CDK4/6 inhibitor therapy. Objective response rate was defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses were evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR was defined as disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).

  Up to 2 years

Secondary Outcomes (3)

• PFS

  Up to 2 years

• CBR

  up to 2 years

• DoR

  Date of CR or PR to date of disease progression or death due to any cause (up to 2 years)

Other Outcomes (1)

• ORR of anlotinib+entinostat+fulvestrant

  Up to 2 years

Study Arms (2)

entinostat + fulvestrant

EXPERIMENTAL

Entinostat tablets Dosage form: Tablets Specification Appearance: 1.0 mg (pink to pale red) or 5.0 mg/ tablet (yellow) Dosage and Administration: 1 tablet (5 mg/ tablet) once a week, orally administered. Take at least 1 hour before meals or at least 2 hours after meals. Combination therapy: Fulvestrant injection Dosage form: Injection Appearance: A clear, viscous, colorless to yellowish liquid Specification: 5 ml; 0.25g per vial Dosage and Administration: 500 mg by intramuscular injection. Each 28-day treatment cycle is administered on day 1 and day 15 of the first cycle, followed by day 1 of each subsequent cycle

Drug: entinostat; Drug: Fulvestrant

entinostat + fulvestrant+anlotinib

EXPERIMENTAL

Entinostat tablets Dosage form: Tablets Specification Appearance: 1.0 mg (pink to pale red) or 5.0 mg/ tablet (yellow) Dosage and Administration: 1 tablet (5 mg/ tablet) once a week, orally administered. Take at least 1 hour before meals or at least 2 hours after meals. Combination therapy: Fulvestrant injection Dosage form: Injection Appearance: A clear, viscous, colorless to yellowish liquid Specification: 5 ml; 0.25g per vial Dosage and Administration: 500 mg by intramuscular injection. Each 28-day treatment cycle is administered on day 1 and day 15 of the first cycle, followed by day 1 of each subsequent cycle Anlotinib capsules Dosage form: Capsule Appearance: White or off-white powder or granules Dosage and Administration: The recommended dose is 10mg each time, once daily, orally before breakfast. Continuous administration 2 weeks, then 1 week off, that is 3 weeks (21 days) as one course of treatment.

Drug: entinostat; Drug: Fulvestrant; Drug: Anlotinib

Interventions

entinostat DRUG

Entinostat tablets, orally once a week (5 mg); Each treatment cycle lasts for 28 days. Treatment will continue until the subject experiences disease progression, intolerable toxicity, voluntary withdrawal, or any other condition specified in the protocol, whichever occurs first.

entinostat + fulvestrant; entinostat + fulvestrant+anlotinib

Fulvestrant DRUG

Fulvestrant, intramuscular injection, 500 mg each time, administered on d1 and d15 of the first cycle, and on d1 of each subsequent cycle. Each treatment cycle lasts for 28 days. Treatment will continue until the subject experiences disease progression, intolerable toxicity, voluntary withdrawal, or any other condition specified in the protocol, whichever occurs first.

entinostat + fulvestrant; entinostat + fulvestrant+anlotinib

Anlotinib DRUG

Anlotinib, 10mg each time, once daily, orally before breakfast. Take the drug for 2 consecutive weeks and then stop for 1 week, that is, 3 weeks (21 days) as one course of treatment.

entinostat + fulvestrant+anlotinib

Eligibility Criteria

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

You may qualify if:

• Sign an informed consent form;
• Female, aged 18 or above;
• The patient's Eastern Tumor Collaboration Group (ECOG) physical status is 0-1;
• The patient's expected survival time is ≥3 months;
• Breast cancer patients diagnosed as HR-positive and HER-2 negative by tumor histopathological and molecular pathological typing (based on the most recent report); 1) Hormone receptor positive refers to estrogen receptor (ER) positive, progesterone receptor (PR) negative or positive (≥1% positive staining cells are considered receptor positive); 2) HER-2 negative means: the immunohistochemical result of the pathological specimen test is 0 or 1+; Or an immunohistochemical result of 2+ and a negative ISH or FISH test.
• The subject has received at least one line of endocrine therapy as well as CDK 4/6 inhibitor therapy at an unresectable stage of locally advanced recurrence or metastasis; Or disease recurrence occurred during ET combined with CDK4/6 inhibitors as adjuvant therapy or within 12 months after the end of treatment.
• The subject has not received chemotherapy or ADC therapy for metastatic disease
• At least one measurable target lesion was evaluated by the investigator in accordance with RECIST 1.1
• No known active brain metastases or leptomeningeal disease
• The patient must have adequate organ function within 1 week (7 days) prior to the initiation of study administration, as defined below:
• Hematology: Hemoglobin (HgB) ≥80 g/L, platelet count ≥100×109 /L, absolute neutrophil count ≥1.0×10 /L.
• Note: Platelet transfusion is not allowed within 3 days before these laboratory tests, red blood cell transfusion is not allowed within 14 days, and hematopoietic growth factor (pegylated G-CSF, 14 days for erythropoietin) is not allowed within 7 days. No blood transfusion or use of auxiliary white blood cell, platelet increase drugs such as cytokines or erythropoietin drugs within 2 weeks prior to the screening test
• Renal function: Serum creatinine (Cre) ≤1.5× upper limit of normal (ULN), or glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2. Urine protein \<2+ or 24-hour urine protein quantification \<1g
• Liver function: Total bilirubin ≤1.5×ULN; If Gilbert syndrome is present, total bilirubin ≤3 mg/dL; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; If there is liver metastasis, both ALT and AST should be ≤5×ULN; Alkaline phosphatase (ALP) ≤2.5×ULN; If there is bone metastasis, it should be ≤5×ULN.
• \. Echocardiography shows left ejection fraction (LVEF) ≥50% and QTc interval ≤480 ms.

You may not qualify if:

• Patients should not be enrolled if any of the following conditions occur:
• Symptomatic visceral metastases or other conditions, visceral crisis, or the investigator deems it inappropriate to use endocrine therapy;
• The patient has a past or present central nervous system metastases, or leptomeningeal disease, brain metastases;
• Previous use of selective estrogen receptor degraders (SERD, such as fulvestrant) or histone deacetylase (HDAC) inhibitors (such as entectamine, chidamide, etc.) or small molecule multi-target tyrosine kinase inhibitors (such as apatinib, anlotinib, etc.) or PAM pathway inhibitors (such as PI3K inhibitor Alpelisib, AKT inhibitor Capivasertib, MTOR inhibitor everolimus, etc.
• Known allergy to SERD, entinostat, or other drugs with a benzamide structure (such as typapride, remopilib, cloprapride, etc.), anlotinib;
• Pregnant or lactating women;
• Coexisting with other malignant tumors, unless radical treatment has been administered and there is no evidence of recurrence or metastasis;
• There is pericardial effusion requiring drainage, pleural effusion with obvious clinical symptoms or ascites;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Zhejiang, Hangzhou, 310000, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

entinostat; Fulvestrant; anlotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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

Rong Wang

CONTACT

18867509858; jiangsuwangrong2006@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Breast Internal Medicine Department

Model Details: The study adopted the Simon phase 2 design, and all 20 eligible patients were treated with entinostat + fulvestrant; The study was terminated if no more than 2 patients achieved objective response and continued to enter Phase 2 if no more than 3 patients achieved objective response. In Phase 2, qualified patients were randomly assigned at a ratio of 1:1.5 to either the entinostat + fluvestrant group (Group 1) or the anlotinib + entinostat + fluvestrant group (Group 2), with 39 patients enrolled in group 1 and 59 patients enrolled in group 2; All patients were treated until the subjects' treatment would continue until the subjects experienced disease progression, intolerable toxicity, active withdrawal from treatment, or other conditions specified in the protocol, whichever occurred first.

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: January 9, 2026
• Study Start: November 24, 2025
• Primary Completion (Estimated): November 25, 2027
• Study Completion (Estimated): November 26, 2028
• Last Updated: January 9, 2026

Record last verified: 2025-11

Locations

CN (1)