Neoadjuvant Culmerciclib Combined With Endocrine Therapy for Hormone Receptor-Positive， Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

NCT07796880 | Recruiting Phase 2

• 1 other identifier: SYSKY-2026-711-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hormone Receptor-Positive Breast Cancer; HER2 Low Breast Carcinoma; Early-Stage Breast Cancer

Keywords

Culmerciclib; Hormone receptor-positive breast cancer; HER2-negative; endocrine therapy; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• 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).

  Within 4 weeks after surgery

Secondary Outcomes (10)

• Pathological complete response rate

  Within 4 weeks after surgery

• Objective response rate

  Within 2 weeks of breast MR examination

• Endocrine Prognostic Index score 0 rate

  Within 4 weeks after surgery

• Complete Cell Cycle Arrest (CCCA) rate

  Within 4 weeks after surgery

• Breast conservation surgery rate

  Within 4 weeks after surgery

Study Arms (2)

Culmerciclib combined with aromatase inhibitor

EXPERIMENTAL

Drug: Culmerciclib; Drug: Aromatase Inhibitor (AI)

Aromatase inhibitor

ACTIVE COMPARATOR

Drug: Aromatase Inhibitor (AI)

Interventions

Culmerciclib DRUG

24 weeks of continuous oral Culmerciclib 180 mg once daily ，continuously

Culmerciclib combined with aromatase inhibitor

Aromatase Inhibitor (AI) DRUG

Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg, administered orally once daily continuously

Aromatase inhibitor; Culmerciclib combined with aromatase inhibitor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

Related Publications (16)

• Song E, Yin Y, Zhao J, et al. LBA25 Culmerciclib plus fulvestrant as first-line treatment for HR+/HER2- advanced breast cancer: A phase III trial (CULMINATE-2). Annals of Oncology. 2025;36:S1569-S1570

  RESULT

• Yin Y, Zhang Q, Sun T, Hao C, Wang Z, Yang J, Wang Y, Shi Y, Sun J, Ouyang Q, Su H, Wu J, Gan L, Han M, Gao L, Wang X, Zhao B, Li H, Zhao J, Yang H, Ning F, Tian F, Zhang J, Sun H, Niu Z, Zong H, Zang A, Wang X, Qian X, Wu S, Nie J, He L, Cheng Y, Hao Y, Zhai Y, Li H, Wang J, Wei S, Li M, Liu Y, Guo H, Hu Q, Liu L, Han X, Luo R, Ni M, Tang X, Zhai Z, Ding M, Wang H, Shen P, Wang X, Liu L, Chen W, Liu G, Cai Z, Jiang Z. Novel CDK2/4/6 inhibitor culmerciclib (TQB3616) plus fulvestrant in previously treated, HR-positive, HER2-negative advanced breast cancer: a randomized, double-blind, phase 3 trial. Signal Transduct Target Ther. 2025 Dec 18;10(1):414. doi: 10.1038/s41392-025-02475-6.

  PMID: 41413016 RESULT

• Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl S, Morris EA, Perez A, Regan MM, Spears PA, Sudheendra PK, Symmans WF, Yung RL, Harvey BE, Hershman DL. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021 May 1;39(13):1485-1505. doi: 10.1200/JCO.20.03399. Epub 2021 Jan 28.

  PMID: 33507815 RESULT

• Jiang Z, Li J, Chen J, Liu Y, Wang K, Nie J, Wang X, Hao C, Yin Y, Wang S, Yan M, Wang T, Yan Y, Chen X, Song E; CSCO BC guideline working group. Chinese Society of Clinical Oncology (CSCO) Breast Cancer Guidelines 2022. Transl Breast Cancer Res. 2022 Apr 30;3:13. doi: 10.21037/tbcr-22-21. eCollection 2022.

  PMID: 38751537 RESULT

• Delaloge S, Dureau S, D'Hondt V, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Lerebours F, Mouret-Reynier MA, Dalenc F, Frenel JS, Jouannaud C, Venat-Bouvet L, Nguyen S, Callens C, Gentien D, Rapinat A, Manduzio H, Vincent-Salomon A, Lemonnier J, Cottu P; French Breast cancer Intergroup Unicancer-UCBG. Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Eur J Cancer. 2022 May;166:300-308. doi: 10.1016/j.ejca.2022.01.014. Epub 2022 Mar 22.

  PMID: 35337692 RESULT

• Wallden B, Storhoff J, Nielsen T, Dowidar N, Schaper C, Ferree S, Liu S, Leung S, Geiss G, Snider J, Vickery T, Davies SR, Mardis ER, Gnant M, Sestak I, Ellis MJ, Perou CM, Bernard PS, Parker JS. Development and verification of the PAM50-based Prosigna breast cancer gene signature assay. BMC Med Genomics. 2015 Aug 22;8:54. doi: 10.1186/s12920-015-0129-6.

  PMID: 26297356 RESULT

• Prat A, Saura C, Pascual T, Hernando C, Munoz M, Pare L, Gonzalez Farre B, Fernandez PL, Galvan P, Chic N, Gonzalez Farre X, Oliveira M, Gil-Gil M, Arumi M, Ferrer N, Montano A, Izarzugaza Y, Llombart-Cussac A, Bratos R, Gonzalez Santiago S, Martinez E, Hoyos S, Rojas B, Virizuela JA, Ortega V, Lopez R, Celiz P, Ciruelos E, Villagrasa P, Gavila J. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020 Jan;21(1):33-43. doi: 10.1016/S1470-2045(19)30786-7. Epub 2019 Dec 11.

  PMID: 31838010 RESULT

• Cottu P, D'Hondt V, Dureau S, Lerebours F, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Mouret-Reynier MA, Dalenc F, Frenel JS, Jouannaud C, Venat-Bouvet L, Nguyen S, Ferrero JM, Canon JL, Grenier J, Callens C, Gentien D, Lemonnier J, Vincent-Salomon A, Delaloge S. Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.

  PMID: 30307466 RESULT

• Yau C, Osdoit M, van der Noordaa M, Shad S, Wei J, de Croze D, Hamy AS, Lae M, Reyal F, Sonke GS, Steenbruggen TG, van Seijen M, Wesseling J, Martin M, Del Monte-Millan M, Lopez-Tarruella S; I-SPY 2 Trial Consortium; Boughey JC, Goetz MP, Hoskin T, Gould R, Valero V, Edge SB, Abraham JE, Bartlett JMS, Caldas C, Dunn J, Earl H, Hayward L, Hiller L, Provenzano E, Sammut SJ, Thomas JS, Cameron D, Graham A, Hall P, Mackintosh L, Fan F, Godwin AK, Schwensen K, Sharma P, DeMichele AM, Cole K, Pusztai L, Kim MO, van 't Veer LJ, Esserman LJ, Symmans WF. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol. 2022 Jan;23(1):149-160. doi: 10.1016/S1470-2045(21)00589-1. Epub 2021 Dec 11.

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• Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017 Apr 1;35(10):1049-1060. doi: 10.1200/JCO.2015.63.1010. Epub 2017 Jan 30.

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• Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006 Apr 20;24(12):1940-9. doi: 10.1200/JCO.2005.02.6187.

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Chang Gong

  Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chang Gong

CONTACT

13925089353; gchang@mail.sysu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start: September 14, 2026
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): March 15, 2033
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: beginning 3 months and ending 5 years following publication of future research article
• Access Criteria: Researchers who provide a methodologically sound proposal, that need to be approved by an approved accredited ethics committee

Locations

CN (1)