Overview

This is a single-center, open-label, randomized phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant Culmerciclib combined with aromatase inhibitor versus aromatase-inhibitor monotherapy in patients with Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative early-stage breast cancer.

Eligibility

Inclusion Criteria:

• Able to understand study procedures, voluntarily participate in the study, and provide written informed consent.
• Female patients aged ≥18 and ≤70 years with histopathologically confirmed untreated unilateral primary invasive breast cancer.
• Hormone-receptor positive (estrogen receptor immunohistochemical expression ≥10%), and HER2-negative (IHC 0-1+, or IHC 2+ with negative FISH test).
• Tumor size \>2 cm or positive regional lymph nodes (TNM stage II-IIIA).
• At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate cardiac function meeting all of the following criteria: i. 12-lead electrocardiogram shows no abnormality or clinically insignificant changes requiring no medical intervention; ii. QTc interval ≤480 ms; iii. No history of torsades de pointes or other symptomatic QTc abnormalities; iv. Left-ventricular ejection fraction (LVEF) ≥50%.
• Adequate bone-marrow reserve: white blood cell count ≥3.0×10⁹/L; absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90 g/L.
• Adequate hepatic and renal function: AST and ALT ≤2.5 × upper limit of normal (ULN); alkaline phosphatase ≤2.5 × ULN; total bilirubin ≤1.5 × ULN; serum creatinine ≤1.5 × ULN.
• For pre-menopausal females or females without surgical sterilization: agree to use effective contraception during study treatment and for at least 6 months after the last dose of study treatment.

Exclusion Criteria:

• Occult breast cancer, inflammatory breast cancer, Paget's disease of the breast, stage IV (metastatic) breast cancer, or bilateral breast cancer.
• Known hypersensitivity to active ingredients or other excipients of study drugs.
• Requirement for additional anti-tumor therapy (excluding ovarian function suppression) during neoadjuvant treatment, as judged by the investigator.
• Prior hormone-replacement therapy that has not been discontinued for at least 2 weeks before study treatment initiation.
• Previous history of anti-tumor chemotherapy, selective estrogen-receptor modulators, or aromatase inhibitor therapy.
• Severe cardiac diseases or conditions that would preclude tolerability of study treatment, including but not limited to: i. Life-threatening arrhythmias or higher-grade atrioventricular block (Mobitz type II second-degree or third-degree atrioventricular block); ii. Unstable angina pectoris; iii. Clinically significant valvular heart disease; iv. Electrocardiogram evidence of transmural myocardial infarction; v. Poorly controlled hypertension.
• Major surgery unrelated to breast cancer within 4 weeks prior to enrollment, or incomplete recovery from such surgical procedures.
• Severe or uncontrolled infections that may interfere with study treatment or outcome assessment, including but not limited to active viral hepatitis, positive human immunodeficiency virus antibody, pulmonary infection.
• History of other malignancies within the past 5 years (except cured carcinoma in-situ of cervix or basal-cell carcinoma of skin).
• Underlying gastrointestinal disorders (especially chronic diarrhea or constipation), inability to swallow, intestinal obstruction, or other conditions interfering with drug intake and absorption.
• Any other condition rendering the patient unsuitable for study participation, in the investigator's opinion