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Phase 2 Trial of KN026+KN046±XELOX in HER2-positive Locally Advanced GC

Primary Purpose

HER2-positive Locally Advanced Resectable Gastric Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
KN026
KN046
XELOX
Sponsored by
Peking University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2-positive Locally Advanced Resectable Gastric Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The subject can understand the informed consent, voluntarily participate and sign the informed consent ; Subjects are older than or equal to 18 years old and younger than or equal to 75 years old on the day of signing the informed consent; Histologically or cytologically confirmed, locally advanced HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma. ECOG score 0 or 1; Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either ECHO (preferred) or MUGA; Liver function met the following criteria within 7 days prior to initial administration: Total bilirubin ≤1.0x ULN (Gilbert's syndrome, or total bilirubin ≤1.5x ULN in liver metastases); Aminotransferase (ALT/AST) ≤1.5x ULN (liver metastatic subjects ≤3xULN); -Renal function within 7 days prior to initial administration: serum creatinine ≤1.5x ULN and serum creatinine clearance ≥60mL/min (according to Cockcroft-Gault Formula calculation); Bone marrow function met the following criteria within 7 days prior to initial administration: Hemoglobin ≥90 g/L; Neutrophil absolute count ≥1.5 x 109/L; Platelet count ≥100x 109/L; INR or PT≤1.5x ULN, and aPTT≤ 1.5x ULN; Life expectancy >3 months; The subjects are able and willing to follow the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol Exclusion Criteria: Existence of other active malignant tumors within 5 years or at the same time. Plan to perform or have undergone an organ or bone marrow transplant. Myocardial infarction and poorly controlled arrhythmias occurred within 6 months prior to the first dose. Existence of grade III - IV cardiac disorders defined by the NYHA or echocardiogram shows: LVEF (left ventricular ejection fraction) < 50%. Human immunodeficiency virus (HIV) infection. Patients with active tuberculosis. Patient with previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severely impaired lung function, etc. Patients who have previously received other antibody/drug treatments for immune checkpoints, such as PD-1, PD-L1, and CTLA4 treatments. Have diseases that may increase the risk of participating in the study and using the study medications, or other severe, acute, and chronic diseases and therefore are judged by the investigator to be unsuitable for clinical studies.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    KN026 combined with KN046

    KN026,KN046 and XELOX

    Arm Description

    KN026 combined with KN046

    KN026,KN046 and XELOX

    Outcomes

    Primary Outcome Measures

    pCR rate
    Pathological complete response (pCR) rate (assessed by central pathology laboratory and the site)

    Secondary Outcome Measures

    Event-free survival (EFS)
    Event-free survival (assessed by the investigator per RECIST v1.1 criteria)
    Disease-free survival (DFS)
    Disease-free survival (assessed by the investigator per RECIST v1.1 criteria)
    overall survival (OS)
    overall survival

    Full Information

    First Posted
    August 8, 2023
    Last Updated
    September 3, 2023
    Sponsor
    Peking University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06023758
    Brief Title
    Phase 2 Trial of KN026+KN046±XELOX in HER2-positive Locally Advanced GC
    Official Title
    A Multicenter II Study to Compare KN026 and KN046 Versus Oxaliplatin, Capecitabine Combined KN026 and KN046 in Patients With HER2-positive Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    September 1, 2025 (Anticipated)
    Study Completion Date
    December 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peking University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    This is a multicenter II study to compare KN026 and KN046 versus Oxaliplatin, Capecitabine combined KN026 and KN046 in patients with HER2-positive locally advanced resectable gastric cancer or gastroesophageal junction adenocarcinoma.
    Detailed Description
    KN026 is an anti-HER2 bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, resulting in dual HER2 signaling blockade.KN046 is a PD-L1 - CTLA-4 bispecific antibody. The trial consists of two groups. All subjects will be treated with KN026 at 30 mg/kg Q3W in combination with KN046 at 5 mg/kg Q3W in Group 1. If the statistical hypothesis is not met in Group 1, patients will be enrolled in Group 2. Patients in group 2 will receive KN026+KN046+XELOX.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HER2-positive Locally Advanced Resectable Gastric Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    18 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    KN026 combined with KN046
    Arm Type
    Experimental
    Arm Description
    KN026 combined with KN046
    Arm Title
    KN026,KN046 and XELOX
    Arm Type
    Experimental
    Arm Description
    KN026,KN046 and XELOX
    Intervention Type
    Drug
    Intervention Name(s)
    KN026
    Intervention Description
    KN026:30 mg/kg Q3W
    Intervention Type
    Drug
    Intervention Name(s)
    KN046
    Intervention Description
    KN046:5 mg/kg Q3W
    Intervention Type
    Drug
    Intervention Name(s)
    XELOX
    Intervention Description
    Oxaliplatin 130mg/m2 d1,Capecitabine 1000mg/m2 d1-14,Q3W
    Primary Outcome Measure Information:
    Title
    pCR rate
    Description
    Pathological complete response (pCR) rate (assessed by central pathology laboratory and the site)
    Time Frame
    up to 2 years
    Secondary Outcome Measure Information:
    Title
    Event-free survival (EFS)
    Description
    Event-free survival (assessed by the investigator per RECIST v1.1 criteria)
    Time Frame
    from enrollment until firstly confirmed and recorded disease progression or death,assessed up to 3 years
    Title
    Disease-free survival (DFS)
    Description
    Disease-free survival (assessed by the investigator per RECIST v1.1 criteria)
    Time Frame
    from the start of surgery to disease recurrence or death (for any reason),assessed up to 3 years
    Title
    overall survival (OS)
    Description
    overall survival
    Time Frame
    From date of randomization until the date of death from any cause, assessed up to 5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: The subject can understand the informed consent, voluntarily participate and sign the informed consent ; Subjects are older than or equal to 18 years old and younger than or equal to 75 years old on the day of signing the informed consent; Histologically or cytologically confirmed, locally advanced HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma. ECOG score 0 or 1; Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either ECHO (preferred) or MUGA; Liver function met the following criteria within 7 days prior to initial administration: Total bilirubin ≤1.0x ULN (Gilbert's syndrome, or total bilirubin ≤1.5x ULN in liver metastases); Aminotransferase (ALT/AST) ≤1.5x ULN (liver metastatic subjects ≤3xULN); -Renal function within 7 days prior to initial administration: serum creatinine ≤1.5x ULN and serum creatinine clearance ≥60mL/min (according to Cockcroft-Gault Formula calculation); Bone marrow function met the following criteria within 7 days prior to initial administration: Hemoglobin ≥90 g/L; Neutrophil absolute count ≥1.5 x 109/L; Platelet count ≥100x 109/L; INR or PT≤1.5x ULN, and aPTT≤ 1.5x ULN; Life expectancy >3 months; The subjects are able and willing to follow the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol Exclusion Criteria: Existence of other active malignant tumors within 5 years or at the same time. Plan to perform or have undergone an organ or bone marrow transplant. Myocardial infarction and poorly controlled arrhythmias occurred within 6 months prior to the first dose. Existence of grade III - IV cardiac disorders defined by the NYHA or echocardiogram shows: LVEF (left ventricular ejection fraction) < 50%. Human immunodeficiency virus (HIV) infection. Patients with active tuberculosis. Patient with previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severely impaired lung function, etc. Patients who have previously received other antibody/drug treatments for immune checkpoints, such as PD-1, PD-L1, and CTLA4 treatments. Have diseases that may increase the risk of participating in the study and using the study medications, or other severe, acute, and chronic diseases and therefore are judged by the investigator to be unsuitable for clinical studies.

    12. IPD Sharing Statement

    Learn more about this trial

    Phase 2 Trial of KN026+KN046±XELOX in HER2-positive Locally Advanced GC

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