Multigene Risk Score Combined With Ki-67 Dynamic Assessment in Stratified Neoadjuvant Endocrine Therapy Treatment With or Without CDK4/6 Inhibitors in HR+/HER2- Breast Cancer

NCT06650748 | Enrolling By Invitation Phase 2 DMC

• 1 other identifier: OBU-BC-II-164
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, randomize-controlled study. The purpose of this study is to evaluate the efficacy of neoadjuvant CDK4/6 inhibitors in patients with high-risk EPclin multigene risk analysis and non-response to Ki-67 2W, and to explore predictive biomarkers for sensitivity to CDK4/6 inhibitor therapy.

Conditions

Breast Cancer; Early-stage Breast Cancer

Keywords

Early-stage Breast Cancer; neoadjuvant endocrine therapy; CDK4/6; HR+/HER2-

Outcome Measures

Primary Outcomes (1)

• 1. The proportion of (PEPI score 0 + pCR) in patients with discordant EPclin scores and Ki67 assessments who were randomly assigned to the "+CDK4/6i" group

  proportion of subjects who were PEPI score 0 or pCR after neoadjuvant endocrine therapy in patients with discordant EPclin scores and Ki67 assessments who were randomly assigned to the "+CDK4/6i" group

  Start of treatment until 6-month follow-up

Secondary Outcomes (12)

• The change in Ki-67 compared to the baseline after two weeks of treatment

  Start of treatment until 2-week follow-up

• The change in Ki-67 after surgery compared to two weeks post-treatment

  Start of treatment until 6-month follow-up

• Rate of patients with pCR (pathological complete response) after surgery

  Start of treatment until 6-month follow-up

• ORR

  Start of treatment until 6-month follow-up

• CCCA rate

  Start of treatment until 6-month follow-up

Study Arms (4)

Arm 1

EXPERIMENTAL

gene high-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks

Drug: Dalpiciclib; Drug: Letrozole

Arm 2

EXPERIMENTAL

gene high-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks and gene low-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks, randomly assigned to letrozole treatment arm

Drug: Letrozole

Arm 3

EXPERIMENTAL

gene high-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks and gene low-risk according to Epclin who are insensitive to single-agent AI treatment for two weeks, randomly assigned to Dalpiciclib and letrozole treatment arm

Drug: Dalpiciclib; Drug: Letrozole

Arm 4

EXPERIMENTAL

gene low-risk according to Epclin who are sensitive to single-agent AI treatment for two weeks

Drug: Letrozole

Interventions

Dalpiciclib DRUG

Dalpiciclib, oral administration, 125g each time, once daily, days 1-21, with a 28-day cycle (3 weeks on/1 week off). Continuous medication for 6 cycles, or disease progression, intolerable toxicity, withdrawal from the study for any reason or death, whichever occurs first; or after researcher's judgement, patient would no longer benefit from the treatment.

Arm 1; Arm 3

Letrozole DRUG

2.5 mg, oral, once daily (continuously), with a 28-day cycle. Continuous medication for 6 cycles, or disease progression, intolerable toxicity, withdrawal from the study for any reason or death, whichever occurs first. Refer to drug instructions for specific usage

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

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

You may qualify if:

• Females aged 18 to 70 years;
• Patients with histologically confirmed HR+/HER2- invasive breast cancer that is sensitive to endocrine therapy. Tumor diameter \>2 cm, clinically positive axillary lymph nodes not more than 2 (T2N1M0), Ki67≥+20%. Endocrine therapy sensitivity is defined as ER expression \>50% by immunohistochemistry. HER-2 negativity is defined as HER-2 results of 0 or 1+ by immunohistochemistry, or negative by FISH;
• Within 28 days before the first dose of study medication, patients must have at least one measurable lesion according to RECIST 1.1 standards, as assessed by ultrasound or MRI;
• Laboratory test values: a. Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 10\^9/L); b. Platelet count (PLT) ≥ 100,000/mm3 (100 × 10\^9/L); c. Hemoglobin (Hb) ≥ 9 g/dL (90 g/L); d. Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 30 ml/min (based on the Cockroft-Gault formula); e. Total bilirubin (BIL) ≤ 1.5 times the upper limit of normal (ULN), Gilbert's syndrome; f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 times the upper limit of normal (ULN); g. INR or PT ≤1.5 ULN, APTT ≤1.5 ULN.
• Subject agrees to collect tumor biopsy specimen during the screening period;
• Subject signed the informed consent form, expressing willingness and ability to comply with the planned visits, study treatments, laboratory tests, and other trial procedures.

You may not qualify if:

• Coexisted with other malignant tumors within 5 years prior to first medication, except for cured squamous cell carcinoma of the skin, basal cell carcinoma, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix/breast, etc;
• Had a serious infection within 1 month before screening or required systemic treatment for any active infection within 2 weeks before first medication;
• History or current presence of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis), autoimmune hepatitis, systemic sclerosis (scleroderma, etc.), Hashimoto's thyroiditis (exceptions are noted below), autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. The following exceptions apply: Type I diabetes, thyroid dysfunction requiring only hormone replacement therapy (including thyroid dysfunction caused by autoimmune thyroid disease), psoriasis or vitiligo not requiring systemic treatment;
• History of organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Patients who received systemic anti-cancer treatment within 2 weeks before the first dose, including chemotherapy, immunotherapy, hormone therapy, biological therapy (cytokines or growth factors that control the progression of cancer);
• Metastatic breast cancer;
• Positive for human immunodeficiency virus antibodies (HIV-Ab) or syphilis antibodies (Anti-TP); positive for hepatitis C virus antibodies (HCV-Ab), with hepatitis C virus RNA quantification \> the upper limit of the normal value of the detection unit; positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (HBcAb), with HBV DNA quantification \> the lower limit of detection of the detection unit;
• History of alcohol abuse or drug abuse.

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

dalpiciclib; Letrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zhaoqing Fan

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)