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.
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).
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.
Parallel
Culmerciclib
Drug24 weeks of continuous oral Culmerciclib 180 mg once daily ，continuously
Aromatase Inhibitor (AI)
DrugAnastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg, administered orally once daily continuously
Rate of participants achieving Residual Cancer Burden (RCB) grade 0 or 1
Proportion of subjects achieving RCB-0 or RCB-1 scores for tumor in the breast tumor bed and regional lymph nodes following neoadjuvant therapy, calculated using the online calculator available on the MD Anderson official website, as assessed by pathologists blinded to treatment assignment. Subjects who discontinued study treatment and received other non-protocol-specified neoadjuvant therapy prior to definitive surgery, subjects who did not undergo surgery, and subjects with missing efficacy information will be categorized as not achieving RCB-0/I (non-responders).
Pathological complete response rate
The proportion of patients with no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ
Objective response rate
The proportion of participants achieving complete response and partial response from the initiation of treatment until disease progression or completion of preoperative neoadjuvant therapy. According to RECIST Version 1.1, intra-breast lesions are evaluated by breast MRI at the end of Week 8 and end of week 24, and after discontinuation of study treatment (if applicable).
Endocrine Prognostic Index score 0 rate
The proportion of participants achieving a score of 0 according to the standard Pre-operative Endocrine Prognostic Index (PEPI) after neoadjuvant therapy
Complete Cell Cycle Arrest (CCCA) rate
Proportion of subjects with Ki67 \< 2.7% after neoadjuvant therapy
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