Study of KN026 Monotherapy or Combination Therapy in Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is an open-label, three-cohort phase 2 study of KN026 in subjects with advanced breast Cancer.

Detailed Description
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KN026 is an anti-HER2 bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, leading to a dual HER2 signal blockade.The HER2- positive mBC subjects without systemic treatment will be enrolled in cohort 1 and received 30 mg/kg KN026 and docetaxol. The HER2 low expression and hormone-receptor positive mBC subjects failed standard chemotherapy and hormone therapy will be enrolled in cohort 2 and received 30 mg/kg KN026 monotherapy. The HER2 low expression and hormone-receptor negative/weak positive mBC subjects failed standard chemotherapy will be enrolled in cohort 3 and received 30 mg/kg KN026 and 5 mg/kg KN046

Official Title
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Phase II Study of Efficacy and Safety Evaluation of KN026 Monotherapy or Combination Therapy in Patients With HER2 Expressing or Positive Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Concurrent chemotherapy and KN026
* Drug: KN026 monotherapy
* Drug: KN026 combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject >= 18 years Histologically/cytologically confirmed, locally advanced unresectable or metastatic breast cancer ECOG score 0 or 1 Life expectancy >3 months According to the definition of RECIST1.1, the patient has at least one measurable lesion Adequate organ function prior to start treatment with KN026 Able to understand, voluntarily participate and willing to sign the ICF Exclusion Criteria: Accepted any other anti-tumor drug therapies within 4 weeks before fist dose Accepted radiotherapy within 4 weeks before enrollment Subjects are eligible with clinically controlled and stable neurologic function >= 4 weeks, which is no evidence of CNS disease progression; Subjects with spinal cord compression and cancerous meningitis are not eligible Pregnant or nursing females；or intend pregnancy within this study period or within 6 monthes after the end of this study History of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation History of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) are not well controlled, and need locally treatment or repeated drainage

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent chemotherapy and KN026<br>KN026 combined with docetaxol | Drug: Concurrent chemotherapy and KN026<br>* 30 mg/kg Q3W KN026 75 mg/m2 docetaxol<br>* Other names: docetaxol;|
| Experimental: KN026 monotherapy<br>KN026 monotherapy | Drug: KN026 monotherapy<br>* 30 mg/kg Q3W KN026<br>* Other names: KN026;|
| Experimental: A combination treatment of KN026 and KN046<br>KN026 combined with KN046 | Drug: KN026 combination<br>* 30 mg/kg Q3W KN026 5 mg/kg Q3W KN046<br>* Other names: KN046;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment | Throughout the duration of the study; up to 2 years | 
| Duration of response (DOR) | Duration of response (DOR) per RECIST 1.1 criteria according to investigators assessment | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest | AEs, SAEs | Throughout the duration of the study | 
| Progression free survival (PFS) rates | Progression free survival (PFS) rates | 6 months and 12 months | 
| Overall survival (OS) rates | Overall survival (OS) rates | 6 months and 12 months | 
| durable benefit rate (DBR) | durable benefit rate (DBR) | DBR calculated as the proportion of subjects with best overall response of CR, PR, or SD ≥24 weeks |