CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment

NCT07366112 | Not Yet Recruiting Phase 2

• 1 other identifier: PKUPH2025CDK46NAE
• Study Type: interventional
• Target: 158
• Locations: 0 countries
• Sites: N/A

Brief Summary

Exploring the dynamics of ctDNA following neoadjuvant therapy with CDK4/6 inhibitors combined with endocrine treatment, and its potential to guide de-escalation of adjuvant chemotherapy

Conditions

Hormone Receptor-Positive Breast Cancer; High-risk Breast Cancer; Early-Stage Breast Cancer; HER2-negative Breast Cancer; ctDNA Monitoring

Outcome Measures

Primary Outcomes (1)

• ctDNA Clearance Rate after Neoadjuvant Therapy

  Proportion of patients achieving conversion from detectable to undetectable ctDNA in plasma after 4 cycles of neoadjuvant CDK4/6i+endocronetherapy. ctDNA analysis uses tumor-informed personalized panels (tracking 16 clonal variants via whole-exome sequencing), with clearance defined as ≥2 consecutive negative results at 1% variant allele frequency threshold.

  From baseline to 4 weeks post-neoadjuvant therapy (pre-surgery)

Secondary Outcomes (5)

• 3-Year Event-Free Survival (EFS)

  From neoadjuvant therapy to 36 months post-surgery

• Residual Cancer Burden (RCB) 0-1 Rate

  At surgery (approximately 16 weeks since neoadjuvant therapy)

• Objective Response Rate (ORR) by RECIST 1.1

  Baseline to pre-surgery (week 16)

• Complete Cell Cycle Arrest (CCCA) Rate (Ki67 ≤2.7%)

  Post-neoadjuvant therapy (pre-surgery, week 16)

• Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs)

  From first dose to 30 days after last treatment

Study Arms (1)

CDK4/6 inhibitor with endocrine therapy

EXPERIMENTAL

Patients receive 4 cycles of neoadjuvant CDK4/6 inhibitor with endocrine therapy. Post-surgery treatment is guided by ctDNA status: ctDNA-negative at baseline and post-neoadjuvant, with post-op Ki67 ≤10% ：Continue CDK4/6 inhibitor with endocrine therapy for 2-3 years. ctDNA-positive → negative, or persistently ctDNA-negative with post-op Ki67 \>10% : Randomized 1:1 to: Arm 1: CDK4/6 inhibitor with endocrine therapy for 2-3 years. Arm 2: Adjuvant chemotherapy (investigator's choice) → CDK4/6 inhibitor with endocrine therapy for 2-3 years. （3）Persistently ctDNA-positive or ctDNA-negative → positive: Adjuvant chemotherapy → CDK4/6 inhibitor with endocrine therapy for 2-3 years. Premenopausal women receive ovarian suppression with LHRH agonists.

Drug: CDK4/6 inhibitor with endocrine therapy

Interventions

CDK4/6 inhibitor with endocrine therapy DRUG

CDK4/6 inhibitor with endocrine therapy for neoadjuvent therapy

CDK4/6 inhibitor with endocrine therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female breast cancer patients aged ≥18 years and ≤75 years, either postmenopausal or premenopausal/perimenopausal; 2.Pathologically confirmed hormone receptor-positive (HR+), HER2-negative invasive breast cancer:
• ER-positive and/or PR-positive defined as: ≥10% of tumor cells showing positive staining;
• HER2-negative defined as: standard immunohistochemistry (IHC) result of 0/1+; or IHC 2+ with negative in situ hybridization (ISH) (confirmed by the central pathology laboratory); 3. At least one evaluable lesion per RECIST 1.1, with clinical staging meeting:
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• T1c-2N0M0 with high-risk factors (Grade 3, or Grade 2 with Ki67 ≥20%);
• T3N0M0;
• Any TN+M0; 4.Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 5.Willing to participate in the study and voluntarily sign informed consent; 6.Agree to undergo ctDNA testing during treatment; 7.Adequate organ and bone marrow function defined as:
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• Absolute neutrophil count (ANC) ≥1,500/mm³ (1.5 × 10⁹/L) (without granulocyte colony-stimulating factor \[G-CSF\] treatment within 14 days);
• Platelet count (PLT) ≥100,000/mm³ (100 × 10⁹/L) (without corrective therapy within 7 days);
• Hemoglobin (Hb) ≥9 g/dL (90 g/L) (without corrective therapy within 7 days);
• Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance ≥60 mL/min (without corrective therapy within 7 days);
• Total bilirubin (TBIL) ≤1.5×ULN (without corrective therapy within 7 days);
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤1.5×ULN (without corrective therapy within 7 days);
• Cardiac function: left ventricular ejection fraction (LVEF) ≥55%; QTc interval corrected by Fridericia's formula (QTcF) \<470 msec on 12-lead ECG; Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and agree to use non-hormonal contraception from informed consent signing until 2 months after the last treatment.

You may not qualify if:

• Bilateral breast cancer; 2.Prior history of breast cancer (including ductal carcinoma in situ or invasive breast cancer); 3.Any prior antitumor therapy for the current breast cancer, including systemic therapies (endocrine, chemotherapy, immunotherapy, biological therapy) or local therapies (radiotherapy, vascular embolization, axillary lymph node biopsy); 4.Diagnosis of any malignancy within 5 years prior to randomization, except cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin; 5.History of severe pulmonary diseases (e.g., interstitial pneumonia); 6. HIV infection, acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥500 IU/mL), hepatitis C (HCV antibody-positive with HCV RNA above the lower limit of detection), or co-infection with HBV and HCV; 7.Within 6 months prior to randomization: myocardial infarction, severe/unstable angina, NYHA Class ≥II heart failure, ≥Grade 2 persistent arrhythmia (per NCI CTCAE v5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or symptomatic pulmonary embolism; 8.Severe active infection within 4 weeks prior to randomization (requiring intravenous antibiotics, antifungals, or antivirals) or unexplained fever \>38.5°C during screening/before first dose; 9.Known allergy to any component of the study drugs; 10.Current participation in another interventional drug clinical study; 11.Pregnancy or lactation; 12.Refusal to comply with follow-up; 13.Other severe physical/mental illnesses or laboratory abnormalities that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.

Sponsors & Collaborators

• Peking University People's Hospital: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• shu wang, doctor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yuan peng, doctor

CONTACT

86+13671287670; 13671287670@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director of breast center

Model Details: All patients receives oral CDK4/6 inhibitor combined with endocrine therapy.

Study Record Dates

• First Submitted: January 18, 2026
• First Posted: January 26, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 26, 2026

Record last verified: 2026-01