Kumorixilib Plus Capecitabine and Letrozole for Neoadjuvant Treatment of HR-Positive HER2-Negative Breast Cancer

An Exploratory Study to Evaluate the Efficacy and Safety of Kumorixilib Combined With Capecitabine and Letrozole as Neoadjuvant Therapy for HR-Positive, HER2-Negative Breast Cancer

This study is a single-center, prospective, open-label exploratory clinical study to assess the efficacy and safety of kumorixilib combined with capecitabine and letrozole as neoadjuvant therapy in patients with HR+/HER2- stage II-III invasive breast cancer. The study plans to enroll 35 eligible patients, and all participants will receive the triple-drug combination regimen without randomization. The treatment regimen: kumorixilib 180 mg orally once daily, capecitabine 500 mg orally three times daily, and letrozole 2.5 mg orally once daily; each cycle lasts 28 days, for a total of 6 cycles. Breast MRI will be used to evaluate radiological tumor response. Surgical resection will be arranged 2-4 weeks after neoadjuvant treatment ends. The primary endpoint is the percentage change in Ki-67 score from baseline to Cycle 1 Day 28. Secondary endpoints include the complete cell cycle arrest rate (CCCA, Ki-67 ≤ 2.7%) on Day 28, the reduction rate of functional tumor volume (FTV), the proportion of patients with RCB 0-1, objective response rate (ORR), and treatment safety. Treatment will be discontinued upon disease progression, intolerable adverse events, withdrawal of consent, or investigator judgment.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Neoplasms; HR+/HER2- Breast Cancer
• Intervention / Treatment: Drug: Kumorixilib 180mg; Drug: Capecitabine 500mg; Drug: Letrozole 2.5mg

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chuangui Song, doctor; Phone Number: 13960709993; Email: songcg1971@outlook.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Provincial Hospital
      • Contact: ruijuan Wang, doctor; Phone Number: 13799367490; Email: Rjwang2025@126.com
    • Fuzhou, Fujian, China, 350001
      • Fujian Cancer Hospital
      • Contact: Chuangui Song, doctor; Phone Number: 13960709993; Email: songcg1971@outlook.com
    • Quanzhou, Fujian, China, 362000
      • The Second Affiliated Hospital of Fujian Medical University
      • Contact: kaiyan Huang, doctor; Phone Number: 15905059388; Email: kaiyanhuang@fjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-

Patients who meet all of the following inclusion criteria are eligible for enrollment in this trial:

1. Female patients with breast cancer aged ≥18 and ≤75 years, satisfying one of the following menopausal status criteria: (1) Bilateral oophorectomy in medical history, or age ≥60 years; (2) Age <60 years with natural menopause (defined as spontaneous cessation of regular menses for at least 12 consecutive months without other pathological or physiological causes), with postmenopausal levels of E2 and FSH; (3) Pre-menopausal or peri-menopausal female patients who are willing to receive LHRH agonist therapy throughout the study period.
2. Histopathologically confirmed estrogen receptor (ER)-positive (>10%) and/or progesterone receptor (PR)-positive (>10%), HER2-negative breast cancer, assessed in accordance with the 2018 ASCO-CAP guidelines. HER2 negativity is defined as immunohistochemistry (IHC) score of 0+, or IHC 2+ with negative in situ hybridization (ISH) test (ISH amplification ratio <2.0), verified by the pathological laboratory.
3. Accept core needle biopsy to provide initial tissue samples with Ki-67 ≥10% tested on the initial specimen; agree to provide tissue samples for tumor biomarker testing and peripheral blood samples for biomarker analysis.
4. Treatment-naïve breast cancer patients staged as Stage II-III per the 8th edition of the AJCC staging system.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

6. Adequate organ function as defined below: Hematologic function: ① Absolute neutrophil count (ANC) ≥1.5×10⁹/L (no growth factor administered within 14 days prior to screening); ② Platelet count ≥100×10⁹/L (no corrective hematologic therapy within 7 days prior to screening); ③ Hemoglobin ≥100 g/L (no corrective hematologic therapy within 7 days prior to screening).

   Hepatic and renal function: ① Total bilirubin ≤1×upper limit of normal (ULN); ② Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN (ALT and AST ≤5×ULN for patients with liver metastases); ③ Blood urea nitrogen and serum creatinine ≤1.5×ULN, with creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula).

7. Cardiac function on echocardiogram: left ventricular ejection fraction (LVEF) ≥50%. 12-lead electrocardiogram (ECG): QT interval ≤480 ms.
8. Able to provide written informed consent prior to any study-related procedures.

Exclusion Criteria:

-

Patients presenting with any of the following conditions are ineligible for enrollment in this study:

1. Prior receipt of any form of anti-tumor therapy (including chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.).
2. Concurrent administration of other anti-tumor agents.
3. Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
4. Stage IV breast cancer.
5. Breast cancer without histopathological confirmation, or refusal to undergo breast core needle biopsy before or during study treatment.
6. History of other malignant tumors within the previous 5 years, except for cured carcinoma in situ of the cervix.
7. Severe dysfunction of vital organs including the heart, liver and kidneys.
8. Conditions interfering with oral drug intake and absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction.
9. Participation in another interventional clinical trial within 4 weeks prior to enrollment.
10. Known hypersensitivity to any components of the study regimen; history of immunodeficiency diseases, including positive human immunodeficiency virus (HIV) test, hepatitis C virus infection, active hepatitis B virus infection, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
11. Prior diagnosis of any cardiac disease, including clinically significant arrhythmias requiring medical intervention, myocardial infarction, heart failure, or any other cardiac disease judged by the investigator to render the patient unsuitable for trial participation.
12. Pregnant or breastfeeding female patients; fertile women with a positive baseline pregnancy test result, or fertile women unwilling to use effective contraception throughout the entire trial period.
13. Coexisting severe medical conditions that may compromise patient safety or interfere with study completion as assessed by the investigator, including but not limited to uncontrolled severe hypertension, uncontrolled severe diabetes, active infections, etc.
14. Confirmed prior history of neurological or psychiatric disorders, including epilepsy or dementia.
15. Any other conditions deemed by the investigator to make the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Kumorixilib + Capecitabine + Letrozole Neoadjuvant Therapy; Patients will receive 6 cycles of neoadjuvant treatment. Each cycle lasts 28 days. The regimen is as follows: kumorixilib 180 mg orally once daily, capecitabine 500 mg orally three times daily, and letrozole 2.5 mg orally once daily. After finishing all treatment cycles, patients will undergo breast surgery 2-4 weeks later.

Drug: Kumorixilib 180mg; Kumorixilib: 180 mg orally once daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.; Drug: Capecitabine 500mg; Capecitabine: 500 mg orally three times daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.; Drug: Letrozole 2.5mg; Letrozole: 2.5 mg orally once daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in Ki-67 score from baseline to Cycle 1 Day 28	The percentage reduction of Ki-67 proliferation index in tumor tissue between baseline and Cycle 1 Day 28 after treatment initiation.	At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete cell cycle arrest (CCCA) rate at Cycle 1 Day 28	Proportion of patients with Ki-67 ≤ 2.7% in tumor tissue at Cycle 1 Day 28	At the end of Cycle 1 (each cycle is 28 days)
Reduction rate of functional tumor volume (FTV)	Percentage shrinkage of functional tumor volume measured by breast MRI	At the end of Cycle 6 (each cycle is 28 days), before breast surgery
Incidence of Residual Cancer Burden (RCB) 0-1	Proportion of patients with RCB grade 0 or 1 on postoperative pathological specimen	After surgical resection (end of neoadjuvant treatment)
Objective Response Rate (ORR)	Proportion of patients achieving complete response (CR) or partial response (PR) assessed by breast MRI	At the end of Cycle 6 (each cycle is 28 days), before breast surgery
Treatment-related adverse events	Incidence and severity of all adverse events related to study treatment	From treatment initiation up to 30 days after the last dose

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital
• Investigators: Principal Investigator: Chuangui Song, doctor, Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nitriles; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Triazoles; Capecitabine; Letrozole
• Other Study ID Numbers: K2026-277-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No