Hormone Receptor-Positive Breast CancerPhase 2NCT07796880
Neoadjuvant Culmerciclib Combined With Endocrine Therapy for Hormone Receptor-Positive， Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer
A Phase 2 study testing Culmerciclib and Aromatase Inhibitor (AI) in people with Hormone Receptor-Positive Breast Cancer and HER2 Low Breast Carcinoma, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Hormone Receptor-Positive Breast Cancer, HER2 Low Breast Carcinoma, Early-Stage Breast Cancer
- What is being tested?
- Culmerciclib and Aromatase Inhibitor (AI)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 14 Sep 2026to 15 Mar 2033
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Adequate cardiac function meeting all of the following criteria:
- 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.
Who cannot join
- 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:
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510120
Chang Gong, 02034070499, gchang@mail.sysu.edu.cn
About this study
Official title: Neoadjuvant Culmerciclib Combined With Endocrine Therapy Versus Endocrine Therapy Alone for Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Breast Cancer: a Single-center, Open-label, Randomized-controlled Phase II Clinical Trial
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
- Being tested
- Culmerciclib, Aromatase Inhibitor (AI)
- Keywords
- Culmerciclib, Hormone receptor-positive breast cancer, HER2-negative, endocrine therapy, neoadjuvant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CulmerciclibDrug
24 weeks of continuous oral Culmerciclib 180 mg once daily ，continuously
Aromatase Inhibitor (AI)Drug
Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg, administered orally once daily continuously
| Study group | Role | What they receive |
|---|---|---|
| Culmerciclib combined with aromatase inhibitor | Experimental | Not described Receives: Drug: Culmerciclib; Drug: Aromatase Inhibitor (AI) |
| Aromatase inhibitor | Active comparator | Not described Receives: Drug: Aromatase Inhibitor (AI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Within 4 weeks after surgery
Secondary outcomes (10)
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
Measured: Within 4 weeks after surgery
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).
Measured: Within 2 weeks of breast MR examination
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
Measured: Within 4 weeks after surgery
Complete Cell Cycle Arrest (CCCA) rate
Proportion of subjects with Ki67 < 2.7% after neoadjuvant therapy
Measured: Within 4 weeks after surgery
Breast conservation surgery rate
The proportion of patients who had successful breast conservation surgery after neoadjuvant therapy
Measured: Within 4 weeks after surgery
Health-related Quality of Life 1
Scores on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30, version 3.0) are linearly transformed to a 0-100 scale for all subscales and single items. The instrument comprises functional scales (physical, role, cognitive, emotional, social), a global health status/quality-of-life scale, and symptom scales/items (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For functional and global health status scales, higher scores indicate better functioning and higher quality of life; for symptom scales, higher scores indicate worse symptoms or greater problems.
Measured: Within 7 days before the first treatment and the end of each cycle (each cycle is 28 days)
Health-related Quality of Life 2
The EORTC Quality of Life Questionnaire Breast Cancer Module (QLQ-BR42) has all subscale and item scores also linearly transformed to a 0-100 scale. The module includes functional subscales (e.g., body image, sexual functioning) and symptom subscales (e.g., systemic therapy side effects, breast symptoms, arm symptoms). Higher scores on functional subscales indicate better functioning, while higher scores on symptom subscales indicate more severe symptoms or side effects.
Measured: Within 7 days before the first treatment and the end of each cycle (each cycle is 28 days)
5-year event-free survival
the time from random assignment until any relapse, unequivocal tumor progression, or any-cause death
Measured: During the 5 years after random assignment
5-year overall survival
the time from random assignment until any-cause death
Measured: During the 5 years after random assignment
Safety (AEs+SAEs)
General safety will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Ovarian toxicity will be evaluated by menstrual status and FSH and E2
Measured: from signing the informed consent form until 2 years after completion of neoadjuvant treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2026
- Study start14 Sep 2026
- Primary completion15 Sep 2028 (estimated)
- Study completion15 Mar 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Hormone Receptor-Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Gong, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Investigators
- Chang Gong, Principal investigator, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07796880
- Sponsor's protocol ID
- SYSKY-2026-711-01
- Status last verified
- Sep 2026
- First submitted
- 27 Aug 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in future research article after de-identification and the study protocol will be shared beginning 3 months and ending 5 years following publication. Proposals should be directed to gchang@mail.sysu.edu.cn and data will be shared by email
Publications
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
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.
PubMed 41413016Korde 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.
PubMed 33507815Jiang 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.
PubMed 38751537Delaloge 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.
PubMed 35337692Wallden 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.
PubMed 26297356Prat 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.
PubMed 31838010Cottu 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.
PubMed 30307466Yau 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.
PubMed 34902335Symmans 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.
PubMed 28135148Kaufmann 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.
PubMed 16622270Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.
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PubMed 18997125Peiffer DS, Zhao F, Chen N, Hahn OM, Nanda R, Olopade OI, Huo D, Howard FM. Clinicopathologic Characteristics and Prognosis of ERBB2-Low Breast Cancer Among Patients in the National Cancer Database. JAMA Oncol. 2023 Apr 1;9(4):500-510. doi: 10.1001/jamaoncol.2022.7476.
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