A Phase III Study of KN026 in Combination With HB1801 as Adjuvant Therapy for Resectable HER2-Positive Breast Cancer

A Randomized, Controlled, Open-label, Multicenter, Phase III Clinical Study to Evaluate the Efficacy and Safety of KN026 Combined With HB1801 and Chemotherapy Versus Trastuzumab Combined With Pertuzumab and Chemotherapy as Adjuvant Therapy in Resectable HER2-positive Breast Cancer

This is a randomized, controlled, open-label, multicenter, Phase Ⅲ clinical study designed to compare the efficacy and safety of KN026 combined with HB1801 and chemotherapy versus trastuzumab combined with pertuzumab and chemotherapy as adjuvant therapy in participants with HER2-positive breast cancer.

Inclusion Criteria:

1. Voluntarily participate and sign the informed consent form.

2. Age ≥ 18 years.

3. ECOG performance status score of 0 or 1.

4. Histologically or cytologically confirmed invasive breast cancer.

5. Must have undergone prior radical mastectomy or breast-conserving surgery for breast cancer.

6. Pathologically confirmed positive regional lymph nodes.

7. Tumor tissue confirmed as HER2-positive by the local laboratory.

8. Adequate organ and bone marrow function:

   1. Absolute neutrophil count ≥ 1.5 × 10⁹/L
   2. Platelet count ≥ 100 × 10⁹/L
   3. Hemoglobin ≥ 90 g/L
   4. Liver function: Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for participants with Gilbert's syndrome); ALT and AST ≤ 2.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN
   5. Coagulation function: INR ≤ 1.5 × ULN and aPTT ≤ 1.5 × ULN
   6. Renal function: Creatinine clearance ≥ 50 mL/min
   7. LVEF ≥ 55%

9. Female participants of childbearing potential must have a negative blood pregnancy test result within 7 days prior to randomization, and agree to use reliable and effective contraception during the study treatment period and for 7 months after the last dose of study treatment. Male participants with female partners of childbearing potential must agree to use reliable and effective contraception during the study treatment period and for 7 months after the last dose of study treatment.

Exclusion Criteria:

1. History of any prior ipsilateral and/or contralateral invasive breast cancer.
2. History of other malignancy within 5 years prior to randomization, except for the breast cancer under study and locally curable malignancies treated with curative intent.
3. Prior systemic chemotherapy, endocrine therapy, anti-HER2 targeted therapy, or local radiotherapy for breast cancer.
4. Use of strong CYP3A4 inhibitors within 14 days prior to randomization or planned use during the combination chemotherapy period.
5. Known contraindication to any study drug or history of hypersensitivity to any component or known excipient of the study drugs.
6. Significant cardiovascular disease history, including: prior coronary artery bypass graft or coronary stenting; myocardial infarction or cerebrovascular accident within 6 months prior to randomization; history of congestive heart failure/systolic dysfunction (LVEF < 50%) or unstable angina; history of clinically significant prolonged QT interval or QTcF (Fridericia) > 450 ms at screening; uncontrolled severe hypertension (systolic BP > 180 mmHg and/or diastolic BP > 100 mmHg); high-risk arrhythmias [e.g., atrial tachycardia with resting heart rate ≥ 100 bpm, significant ventricular arrhythmia (ventricular tachycardia), or high-grade atrioventricular block (Mobitz type II second-degree or third-degree AV block)].
7. Severe chronic or active infection requiring intravenous anti-infective therapy within 14 days prior to randomization.
8. Participation in another interventional clinical trial within 4 weeks prior to randomization.
9. Pregnant or lactating women.
10. Any other condition that may interfere with the participant's ability to comply with study procedures, may not be in the participant's best interest to participate, or may affect study results (e.g., history of neurological or psychiatric disorders, alcohol or drug abuse, or any other clinically significant disease or condition).