Study of KN026 in Combination With Palbociclib and Fulvestrant in Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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This is an open-label, multicenter, dose-escalation and parallel-group expansion Phase II clinical trial to evaluate the efficacy, safety and tolerability of KN026 in combination with palbociclib and fulvestrant in women or male with HER2-positive metastatic breast cancer .The subjects will receive 20 mg/kg IV Q2W+ palbociclib 100/125 mg/day orally+/-Fulvestrant 500 mg IM until progressive disease, unacceptable toxicity or death.

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.

Official Title
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A Phase II Study to Evaluate Efficacy, Safety and Tolerability of KN026 in Combination With Palbociclib and Fulvestrant in Patients With Locally Advanced HER2-positive Breast Cancer

Conditions
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HER2-positive Metastatic Breast Cancer

Intervention / Treatment
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* Drug: KN026 combined with Palbociclib and Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject >= 18 years; Histologically or cytologically confirmed, metastatic or locally advanced unresectable HER2-positive; Adequate organ function assessed within 7 days prior to first trial treatment ECOG score 0 or 1; Left ventricular ejection fraction (LVEF) ≥ 50% at baseline; Life expectancy >3 months Exclusion Criteria: Untreated active CNS metastasis or leptomeningeal metastasis; Uncontrolled tumor-related pain; Has received other anti-tumor treatment or an investigational drug within 28 days or within 5 times of half-life (whichever is shorter, and no less than 2 weeks) prior to the first trial treatment; Major surgery for any reason within 28 days; Curative radiation within 3 months of the first dose of trial treatment; History of uncontrolled intercurrent illness; Other medical conditions that at the discretion of investigator interfere with the requirements of the trial in terms of safety or efficacy evaluation, or treatment compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| dose-escalation Phase<br>KN026 20 mg/kg + palbociclib125 mg/day+Fulvestrant 500 mg (Patients with HR+/HER2-positive MBC ) | |
| parallel-group expansion Phase<br>KN026 20 mg/kg + palbociclib +Fulvestrant 500 mg(Patients with HR+/HER2-positive MBC ) | Drug: KN026 combined with Palbociclib and Fulvestrant<br>* HR+/HER2-positive MBC will be treated by KN026 20 mg/kg+Palbociclib+fulvestrant 500 mg<br>* Other names: combination;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | The proportion of patients experiencing dose limiting toxicities | up to 24 weeks | 
| Objective response rate (ORR) | ORR as assessed by the investigator according to RECIST 1.1 | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) | clinical response time (DOR) as determined by investigators based on RECIST 1.1 criteria | through study completion, an average of 1 year | 
| Progression free survival (PFS) rates | Progression free survival (PFS) rates | 6 months and 12 months | 
| Overall survival (OS) | Overall survival (OS) rates | 6 months and 12 months | 
| Clinical benefit rate (CBR) | Clinical benefit rate | CBR calculated as the proportion of subjects with best overall response of CR, PR, or SD ≥24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KN026, palbociclib, HER2-positive MBC