A Study of Entinostat in Combination With Fulvestrant for the Treatment of Locally Advanced or Metastatic Breast Cancer

NCT07235618 | Not Yet Recruiting Phase 2

• 1 other identifier: EOC103D201
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy of Entinostat combined with Fulvestrant in HR+/HER2- advanced breast cancer patients with recurrence/progression after endocrine therapy (primary endpoint: progression-free survival \[PFS\]), and explore the correlation between peripheral blood mononuclear cell (PBMC) acetylation levels and treatment response to determine the baseline acetylation threshold .

Conditions

Locally Advanced or Metastatic Breast Cancer

Keywords

Locally Advanced or Metastatic Breast Cancer; Entinostat; Fulvestrant; HR positive and HER2 negtive

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression-free survival(PFS) is defined as the time from treatment initiation to disease progression or death from any cause.

  Up to 1 year

Secondary Outcomes (7)

• Overall Survival(OS)

  Up to 3 years

• Objective Response Rate(ORR)

  Up to 3 years

• Clinical Benefit Rate(CBR)

  Up to 3 years

• Duration of response(DOR)

  Up to 3 years

• Health-Related Quality of Life

  Up to 3 years

Other Outcomes (1)

• Biomarker analysis(protein lysine acetylation of peripheral blood samples (PBMCs))

  Up to 1 year

Study Arms (1)

Entinostat + Fulvestrant

EXPERIMENTAL

Drug: Entinostat; Drug: Fulvestrant

Interventions

Entinostat DRUG

Entinostat (5mg/week, po)

Entinostat + Fulvestrant

Fulvestrant DRUG

Fulvestrant( 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28-day cycle)

Entinostat + Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form.
• Female participants aged ≥18 and ≤75 years. 3 .Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• \. Life expectancy ≥3 months. 5.Participants must have histopathologically and molecular pathologically diagnosised HR-positive and HER2-negative breast cancer (based on the most recent report),defined as presence of following criteria:
• Hormone receptor positivity is defined by the presence of estrogen receptors (ER), where a threshold of ≥10% positive staining cells is considered indicative of positivity. The status of progesterone receptors (PR) can be either negative or positive, with the same criterion of ≥10% positive staining cells applied to determine receptor positivity.
• HER-2 negativity indicates that the immunohistochemical assessment of the pathological specimen yields a result classified as 0 or 1+. Alternatively, a result classified as 2+ may also be deemed HER-2 negative if corroborated by negative findings from ISH or FISH testing.
• \. Participants must have received endocrine +CDK4/6 inhibitor treatment and meet any of the following conditions, namely endocrine resistance:
• a) Imaging progression occurs during adjuvant/neoadjuvant endocrine therapy; or b) Recurrence/metastasis within ≤12 months after the completion of adjuvant endocrine therapy; or c) Disease progression occurred after first-line endocrine therapy in the advanced stage (RECIST v1.1).
• Prior chemotherapy history for the participants must meet:
• For metastatic diseases, having received ≤1 line of chemotherapy (including antibody-drug conjugates) in the past;
• The period from the end of the last chemotherapy administration to the randomization date is ≥4 weeks;
• If disease progression occurs within ≤12 months after the end of neoadjuvant or adjuvant chemotherapy, this regimen is regarded as first-line chemotherapy in the metastasis stage.
• One week (7 days) before the start of the study administration, the participant must have adequate organ function, as defined below: Hematology: Hemoglobin (HgB) ≥80 g/L, platelet count ≥50×109 /L, absolute neutrophil count ≥1.0×109 /L.
• Note: Before these laboratory tests, platelet transfusion is not allowed within 3 days, red blood cell transfusion is not allowed within 14 days, and hematopoietic growth factor (pegylated G-CSF and erythropoietin within 14 days) is not allowed within 7 days.
• Renal function: Serum creatinine (Cre) ≤1.5× upper limit of normal (ULN), or glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2.
• Liver function: Total bilirubin ≤1.5×ULN; If Gilbert syndrome is present, the total bilirubin is ≤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.

You may not qualify if:

• Presence of current or prior Central Nervous System (CNS) metastases or leptomeningeal disease (LMD).
• Prior treatment with Selective Estrogen Receptor Degraders (SERD, e.g., fulvestrant) or Histone Deacetylase (HDAC) inhibitors (e.g., entinostat, chidamide).
• Known to be allergic to SERD, entinostat or other drugs with a benzamide structure (such as tyapride, remopilib, cloprapride, etc.).
• Pregnant or lactating women.
• Combined with other malignant tumors, unless radical treatment has been carried out and there is no evidence of recurrence or metastasis;
• Clinically significant effusions requiring drainage (e.g., pericardial, pleural, or ascites with symptoms).
• Significant clinical gastrointestinal dysfunction that may affect oral medication intake, transport, or absorption(e.g., dysphagia, chronic diarrhea, intestinal obstruction).
• Severe infectious diseases, uncontrolled or severe cardiovascular diseases, or other abnormalities within 14 days before enrollment that the investigators considered might affect the safety and compliance of the subjects and were not suitable for participation in this clinical trial.
• Participants deemed by investigators as unsuitable for endocrine therapy.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

entinostat; Fulvestrant

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

Shusen Wang, MD

CONTACT

+86-02087342491; wangshs@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 19, 2025
• Study Start: January 5, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)