Brief Summary This is an open-label, randomized, phase II clinical study designed to evaluate neoadjuvant treatment regimens in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.
A total of 60 premenopausal, perimenopausal, and postmenopausal patients with HR+/HER2- breast cancer who meet the inclusion criteria will be enrolled. During the study, clinical information will be collected according to standard practice, including demographic data, tumor imaging, and pathological results (e.g., Ki-67). Investigator-assessed outcomes will be used as the final results.
After 14 days of treatment, patients who provide consent will undergo a second biopsy to evaluate the rate of complete cell-cycle arrest. Safety assessments and imaging evaluations will be performed at treatment completion or upon study withdrawal. Informed consent must be obtained at each study center before participation.
Treatment arms:
Arm A (30 patients):
Dalpiciclib 125 mg orally once daily on Days 1-21 of each 28-day cycle (3 weeks on, 1 week off), for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Entinostat 3 mg orally once weekly (Days 1-28 of each 28-day cycle), for 6 cycles
Arm B (30 patients):
Dalpiciclib 150 mg orally once daily on Days 1-21 of each 28-day cycle, for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Premenopausal and perimenopausal women will also receive ovarian function suppression (OFS), such as with a GnRHa agent.
After signing informed consent, patients will begin neoadjuvant therapy with dalpiciclib plus entinostat and letrozole ± OFS. Ultrasound assessments will be conducted every two treatment cycles and before surgery under the same imaging conditions as baseline. Bone scans will be performed at the end of neoadjuvant treatment. MRI of the breast will be performed at baseline, after two cycles, and before surgery to assess treatment efficacy. Treatment discontinuation will occur if toxicity is intolerable, consent is withdrawn, or the investigator determines it is necessary.
Adjuvant therapy:
After surgery, patients will receive physician's choice of therapy (TPC).
Safety follow-up:
Patients will be followed until they start another anticancer therapy, all adverse events have resolved to Grade 0-1 or baseline level, or death-whichever occurs first.
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.
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).
At least one measurable lesion according to RECIST 1.1; clinical stage T1c-T2, cN1-2, or T3-T4, cN0-2.
No prior anticancer therapy for breast cancer, including chemotherapy,endocrine therapy, or targeted therapy.
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.
Bilateral breast cancer or inflammatory breast cancer.
Stage IV (metastatic) breast cancer at initial diagnosis.
History of congestive heart failure, unstable angina, significant arrhythmia, or myocardial infarction.
Parallel
entinostat
DrugEntinostat is added in the experimental arm, while the control arm does not receive Entinostat.
Dalpiciclib
DrugDalpiciclib is both added in the experimental arm and control arm.
Letrozole
DrugLetrozole is both added in the experimental arm and control arm.
ORR
Objective Response Rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed according to RECIST v1.1 criteria. Tumor response must be confirmed by repeat imaging at least 4 weeks after the initial documentation of response.
tpCR
Total pathological complete response (tpCR) is defined as the absence of residual invasive cancer in both the breast and axillary lymph nodes following neoadjuvant therapy, corresponding to ypT0/Tis, ypN0.
Breast-conserving surgery (BCS) rate
Breast-conserving surgery rate is defined as the proportion of participants who undergo breast-conserving surgery (lumpectomy) among all participants who proceed to definitive breast surgery after completion of neoadjuvant therapy. The classification of breast-conserving surgery is based on the operative report and pathology assessment.
Proportion of participants achieving PEPI 0
PEPI 0 (Preoperative Endocrine Prognostic Index score of 0) is defined as meeting all of the following criteria at surgery after completion of neoadjuvant endocrine-based therapy: Pathologic tumor size: ypT1 or smaller (≤2 cm) Nodal status: ypN0 (no metastatic involvement in regional lymph nodes) Ki-67 proliferation index: ≤2.7% in the surgical specimen Estrogen receptor (ER): Allred score of 3-8 (ER-positive) Participants meeting all components are classified as achieving PEPI score = 0, indicating an extremely low risk of relapse.
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Hebei Medical University Fourth Hospital
Lead sponsor
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Collaborator
