Efficacy and Safety of KN026 in Combination With HB1801 in the First-line Treatment of Subjects With HER2-positive Recurrent or Metastatic Breast Cancer.

Study Overview
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Brief Summary
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This is a randomized, controlled, open-label, multicenter, phase Ш clinical study designed to compare the efficacy and safety of KN026 in combination with HB1801 to trastuzumab in combination with pertuzumab and docetaxel in the first-line treatment of subjects with HER2-positive recurrent or metastatic breast cancer. The statistical assumption for this study is superiority. The primary study endpoint was PFS as assessed by Blinded Independ Review Committee (BIRC).

Detailed Description
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The purpose of this study is to assess the efficacy and safety of KN026 combined with HB1801 versus trastuzumab combined with pertuzumab and docetaxel as first-line treatment for HER2-positive recurrent or metastatic breast cancer. This study will establish an independent data monitoring committee (IDMC) to conduct safety assessments after approximately 20 subjects in the treatment group complete the first cycle of treatment. During the safety assessment period, the study will continue to enroll subjects, and safety review meetings will be at 1 year of randomization in the first subject. In addition, the IDMC plans to conduct one interim analysis of efficacy during the study period. The primary study hypotheses are that the combination of KN026 combined with HB1801 is superior to trastuzumab combined with pertuzumab and docetaxel with respect to: Progression-free Survival (PFS) as assessed by the BIRC per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Official Title
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A Randomized, Controlled, Open-label, Multicenter, Phase Ш Clinical Study of the Efficacy and Safety of KN026 in Combination With HB1801 Versus Trastuzumab in Combination With Pertuzumab and Docetaxel in the First-line Treatment of Subjects With HER2-positive Recurrent or Metastatic Breast Cancer.

Conditions
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First-line Treatment of HER2-positive Recurrent or Metastatic Breast Cancer

Intervention / Treatment
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* Drug: KN026
* Drug: HB1801
* Drug: Pertuzumab
* Drug: Trastuzumab
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Voluntarily enrolled in this study and signed an informed consent form (ICF). Age ≥ 18 years. Recurrent or metastatic breast cancer confirmed by histology and/or cytology. Latest tumor tissue sample confirmed as HER2 positive by central laboratory testing. No prior systemic chemotherapy and/or HER2-targeted therapy for recurrent or metastatic breast cancer. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 - 1. Presence of lesion (RECIST 1.1). Adequate organ and bone marrow function Key Exclusion Criteria: Ineligible for any of the agents on the study Untreated or unstable parenchymal metastases, spinal cord metastases or compression, or carcinomatous encephalitis. Pregnant or lactating women. Presence of other circumstances that may interfere with the subject's participation in the study procedures or are inconsistent with the maximum benefit of the subject's participation in the study or affect the results of the study: e.g., history of mental illness, drug or substance abuse, any other disease or condition of clinical significance, etc.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN026+HB1801<br>Subjects will receive an intravenous (IV) infusion of KN026 plus HB1801. All subjects are required to receive study treatment as planned until investigator-assessed loss of benefit, toxic intolerance, withdrawal of consent, loss to follow-up, or death, whichever occurrs first. | Drug: KN026<br>* IV infusion<br>Drug: HB1801<br>* IV infusion<br>|
| Active Comparator: Trastuzumab + Pertuzumab + Docetaxel<br>On Day 1 of each 21-day cycle, patients will receive an intravenous (IV) infusion of Pertuzumab 840 mg loading dose followed by 420 mg per cycle, IV, D1, Q3W, in combination with trastuzumab 8 mg/kg loading dose followed by 6 mg/kg per cycle, IV, D1, Q3W and docetaxel 75 mg/m^2. All subjects are required to receive study treatment as planned until investigator-assessed loss of benefit, toxic intolerance, withdrawal of consent, loss to follow-up, or death, whichever occurred first. | Drug: Pertuzumab<br>* 840 mg loading dose followed by 420 mg per cycle, D1 Q3W, IV infusion<br>Drug: Trastuzumab<br>* 8 mg/kg loading dose followed by 6 mg/kg per cycle, D1 Q3W, IV infusion<br>Drug: Docetaxel<br>* 75 mg/m^2, D1 Q3W, IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free-progression survival (PFS) as evaluated by BIRC (RECIST1.1). |  | Up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (investigator assessment, RECIST1.1) |  | Up to approximately 4 years | 
| Overall survival (OS) |  | Up to approximately 4 years | 
| Objective response rate (ORR) |  | Up to approximately 4 years | 
| Disease control rate (DCR) |  | Up to approximately 4 years | 
| Duration of response (DoR) |  | Up to approximately 4 years | 
| Frequency and severity of TEAE and SAE |  | Up to approximately 4 years | 
| Concentration of KN026 in serum |  | Up to approximately 4 years | 
| Concentration of HB1801 in serum |  | Up to approximately 4 years | 
| Incidence of KN026 Anti-drug antibody (ADA) and neutralizing antibody (Nab) (if applicable) |  | Up to approximately 4 years |