KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor

Study Overview
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Brief Summary
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This is a phase Ib, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of KN026 combined with KN046 in subjects with advanced HER2 positive solid tumors.

Detailed Description
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The study is composed of 2 stages. Stage 1 consists of dose escalation cohorts for determining the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 consists of 4 tumor type expansion cohorts for expanding the information on clinical safety, clinical pharmacokinetics and antitumor activity in HER2 positive patients.

Official Title
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A Phase Ib Study to Evaluate Efficacy, Safety and Tolerability of KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor

Conditions
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HER2 Positive Solid Tumor

Intervention / Treatment
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* Biological: KN026 combined with KN046


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed inform consent form (ICF) Age ≥ 18 years and ≤ 75 years, male or female Histologically or cytologically documented advanced HER2 positive solid tumor Received at least one prior standard therapy At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function LVEF≥ 50% (ECHO) Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed. Ability to comply with treatment, procedures and pharmacokinetics (PK) sample collection and the required study follow-up procedures Exclusion Criteria: Accepted any other anti-tumor drug therapies within 4 weeks before fist dose Accepted radiotherapy within 4 weeks before enrollment An anthracyclines antibiotic treatment was received exceeding 320 mg/m² or other equivalent dose antharcyclines 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 Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement doses, equivalent to < 10 mg prednisone daily, inhaled steroids and topical use of steroids) Vaccination within 28 days of the first administration of trial treatment, except for administration of inactivated vaccines (e.g., inactivated influenza vaccines) Pregnant or nursing females；or intend pregnancy within this study period or within 6 monthes after the end of this study Severe chronic and active infection, need to system antibiosis/antiviral treatment Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management 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
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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN026 combined with KN046<br>KN026 is an anti-HER2 bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, leading to a dual HER2 signal blockade. KN046 is a PD-L1 - CTLA-4 bispecific antibody. | Biological: KN026 combined with KN046<br>* KN026 and KN046 are given at 20mg/Kg and 3mg/Kg intravenously on day 1of each 2 weeks cycle at the beginning respectively.The dosage will be escalated if adverse events are tolerated according to the scheme.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity（DLT） | Dose-limiting toxicity | 28 days | 
| Objective response rate (ORR) | Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment | 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 |
| --- | --- | --- |
| Clinical benefit rate | Clinical benefit rate | up to 2 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KN026, KN046, HER2 Positive Solid Tumor