Dalpiciclib with or without entinostat plus letrozole for HR-positive, HER2-negative early breast cancer

An Open-Label, Randomized, Phase II Study of Dalpiciclib in Combination With Entinostat and Letrozole Versus Dalpiciclib Plus Letrozole as Neoadjuvant Therapy in Patients With HR-positive, HER2-negative Early Breast Cancer

This tests whether adding the CDK4/6 drug dalpiciclib, with or without the HDAC blocker entinostat, to the hormone pill letrozole helps shrink tumors in people with HR+/HER2- early breast cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Hebei Medical University Fourth Hospital (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shijiazhuang, Hebei)
• Trial ID: NCT07492394 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized phase II neoadjuvant study enrolling 60 premenopausal, perimenopausal, and postmenopausal patients with ER-positive (>10%), HER2-negative early or locally advanced breast cancer. Participants are randomized to receive dalpiciclib with letrozole, with or without entinostat, before surgery and clinical data including imaging and pathology (including Ki-67) are collected per standard practice. A second tumor biopsy is taken after 14 days in consenting patients to measure complete cell-cycle arrest, and outcomes are investigator-assessed with safety and imaging evaluated at treatment completion or withdrawal. The study compares biological and clinical responses across the regimens to see if adding dalpiciclib and/or entinostat improves neoadjuvant endocrine therapy.

Who should consider this trial

Good fit: Ideal candidates are adults (18–74) with untreated ER-positive (>10%), HER2-negative early or locally advanced breast cancer who have at least one measurable lesion and are willing to undergo neoadjuvant hormone-based therapy and biopsy.

Not a fit: Patients with HER2-positive disease, prior systemic therapy for their current breast cancer, very small/non-measurable tumors, or significant comorbidities that prevent study treatments are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could increase tumor shrinkage from endocrine therapy, potentially enabling more breast-conserving surgery and avoiding or delaying chemotherapy.

How similar studies have performed: Previous DAWNA studies have supported dalpiciclib's activity in breast cancer, while prior trials of HDAC inhibitors like entinostat have shown mixed results.

Eligibility criteria

Inclusion Criteria:

\- Inclusion Criteria

1. Female patients aged ≥18 and \<75 years, including postmenopausal, premenopausal, or perimenopausal. Postmenopause is defined as:Prior bilateral oophorectomy, or age ≥60 years; orAge \<60 years, natural postmenopause (spontaneous cessation of menses for ≥12 months without other pathological or physiological cause) with estradiol (E2) and FSH in postmenopausal range; orPremenopausal or perimenopausal women willing to receive LHRH agonist (OFS) therapy during the study.
2. Histologically confirmed estrogen receptor (ER)-positive (\>10%) invasive breast cancer, regardless of PR expression, and HER2-negative according to the 2018 ASCO/CAP HER2 testing guidelines (IHC 0+ or IHC 2+ with ISH-negative, amplification ratio \<2.0).
3. At least one measurable lesion according to RECIST 1.1; clinical stage T1c-T2, cN1-2, or T3-T4, cN0-2.
4. No prior anticancer therapy for breast cancer, including chemotherapy,endocrine therapy, or targeted therapy.
5. Ability to swallow oral medications.
6. Baseline left ventricular ejection fraction (LVEF) ≥50%.
7. Adequate organ function:Hematology (within 1 week):Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;White blood cell count (WBC) ≥3.0 × 10⁹/L;Platelet count ≥90 × 10⁹/L;Hemoglobin ≥90 g/L Liver and kidney function (within 1 week):Total bilirubin (TBIL) ≤ upper limit of normal (ULN);ALT and AST ≤1.5 × ULNBUN and creatinine ≤1.5 × ULN, with creatinine clearance ≥60 mL/min (Cockcroft-Gault formula)
8. ECG: Corrected QT interval ≤470 ms (12-lead ECG)
9. Willingness and ability to undergo all required biopsy procedures.
10. Women of childbearing potential must have a negative pregnancy test before study entry and agree to use medically acceptable contraception during the study; postmenopausal women are exempt.
11. Voluntary participation with signed informed consent, good compliance, and willingness to adhere to follow-up requirements.

Exclusion Criteria:

\- Exclusion Criteria

1. Pregnant or breastfeeding women, or women with a positive pregnancy test at baseline; women of childbearing potential unwilling to use effective contraception during the study.
2. Bilateral breast cancer or inflammatory breast cancer.
3. Stage IV (metastatic) breast cancer at initial diagnosis.
4. History of congestive heart failure, unstable angina, significant arrhythmia, or myocardial infarction.
5. Active pulmonary disease, including interstitial lung disease, pneumonia, pulmonary fibrosis, or other acute lung conditions.
6. Significant liver disease, such as acute or fulminant hepatitis, impaired coagulation factor synthesis, or other severe hepatic dysfunction.
7. For patients positive for HBsAg or HBV core antibody, peripheral blood HBV DNA must be \<1×10³ IU/mL to be eligible.
8. Any concurrent disease or condition that may interfere with study participation or affect patient safety (e.g., active or uncontrolled infection).
9. Other invasive malignancies (including second primary breast cancer) that may interfere with study outcomes or compliance.
10. Prior chemotherapy, endocrine therapy, or biologic therapy for breast cancer (except diagnostic biopsy for primary breast cancer).
11. Major surgery within 4 weeks prior to study entry or unresolved significant medical conditions.
12. Tumors that are non-measurable during the study treatment.
13. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation.

Where this trial is running

Shijiazhuang, Hebei

• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (RECRUITING)

Study contacts

• Study coordinator: Zhenchuan Song

Conditions: Breast Cancer