Study of Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate in HER2-positive or Mutated Advanced Colorectal Cancer Who Failed Standard Therapy
Primary Purpose
HER2-positive or Mutated Advanced Colorectal Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tislelizumab
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive or Mutated Advanced Colorectal Cancer focused on measuring HER2-positive or Mutated, Advanced Colorectal Cancer, failure of standard treatment, Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate, PD-1 inhibitors+ADC+TKI
Eligibility Criteria
Inclusion Criteria:
- Colorectal cancer patients aged ≥18 years and ≤75 years old;
- ECOG score 0~1 points;
- Pathologically confirmed HER2 amplification-positive or mutated patients with advanced colorectal cancer who have failed or are intolerant of first-line therapy;
- Note: HER2 amplification positive means that in the pathological detection/recheck of the primary tumor or metastases conducted by the pathology department of our hospital, at least one tumor cell immunohistochemical staining intensity is 3+ or immunohistochemical staining intensity is 2+ and has been Fluorescence in situ hybridization [FISH] confirmed positive or NGS confirmed advanced colorectal cancer patients with HER2 gene amplification or mutation.
- According to RECIST1.1 criteria, there is at least one measurable target lesion, and tumor imaging evaluation is performed within 28 days before the first dose;
- Expected survival time ≥ 12 weeks;
Major organ function is normal, that is, the following criteria are met:
- The blood routine examination standards must meet: ANC ≥1.5×109/L; PLT ≥90×109/L; Hb ≥90g/L (no blood transfusion within 14 days);
- Biochemical examinations should meet the following criteria: ALB≥30g/L; (no ALB transfusion within 14 days); TBIL≤Upper limit of normal (ULN); ALT and AST≤2.5 times upper limit of normal (ULN), if there is liver metastasis , then ALT and AST≤5ULN; alkaline phosphatase≤2.5 times the upper limit of normal (ULN); BUN and Cr≤1.5×ULN and creatinine clearance rate≥50 mL/min (CockcroftGault formula);
- Cardiac ultrasound and echocardiography: left ventricular ejection fraction (LVEF≥50%);(4) QT interval (QTcF) corrected by Fridericia method of 18-lead ECG in females <470 ms;
- For premenopausal or surgically sterilized female patients: consent to abstinence or use of effective contraception during treatment and for at least 7 months after the last dose of study treatment;
- Voluntarily join the study and sign the informed consent
Exclusion Criteria:
- Patients who have not received first-line standard therapy;
- Previous antitumor therapy or radiation therapy for any other malignant tumor;
- concurrently receiving anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy, and immunotherapy;
- Has undergone major surgical procedures not related to colorectal cancer within 4 weeks prior to enrollment, or the patient has not fully recovered from such surgical procedures;
Serious heart disease or discomfort, including but not limited to the following:
- Diagnosed history of heart failure or systolic dysfunction (LVEF < 50%)
- High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate >100 bpm, significant ventricular arrhythmia (eg, ventricular tachycardia), or higher-grade AV block (ie, Mobitz II second-degree AV block or third-degree AV block)
- Angina pectoris requiring antianginal drug treatment
- Clinically significant heart valve disease
- ECG showing transmural myocardial infarction
- Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
- Inability to swallow, bowel obstruction, or other factors that interfere with drug taking and absorption;
- Known history of allergy to the drug components of this regimen; history of immunodeficiency, including HIV positive test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
- Pregnant or lactating female patients, female patients of childbearing potential with a positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period and within 7 months after the last study drug;
- have serious comorbidities or other comorbidities that would interfere with planned treatment, orAny other conditions for which the patient was deemed unsuitable for participation in this study by the investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate
Arm Description
One arm study
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
It is defined as the number of subjects with the best response effect as complete remission (CR) or partial remission (PR) during the period from the start of the subjects receiving the treatment regimen of this study to the progression of the subjects' disease in the total number of subjects in the analysis data set. percentage of the population(%).
Secondary Outcome Measures
Disease Control Rate (DCR)
Defined as the number of subjects whose tumors shrank or remained stable for a certain period of time from receiving the treatment regimen of this study to the progression of the subject's disease, including complete remission (CR) and partial remission (PR) in the analysis data set percentage of the total population(%).
Progression Free Survival (PFS)
Defined as the time from randomization to tumor progression in any aspect or death from any cause(Unit: month).
Assessed according to RECIST 1.1 criteria, analysis of this indicator included tumor evaluation results during study treatment and follow-up. If the patient has several indicators that can be judged as PD, the first indicator will be used for PFS analysis; recurrence, new lesions or death are considered to have reached the end of the study, and the patient is treated with other systemic or target-targeted anti-PD. Tumor treatment is also considered tumor progression.
Overall survival (OS)
Defined as the time from randomization to death from any cause(Unit: month).
Drug-Related Safety Indicators
Exposure to the investigational drug and incidence, nature, and severity of adverse events, including serious adverse events(n,%)。
Study on the mechanism of drug resistance after progression
Changes in HER2 status, HER2 gene, and HER2-related signaling pathways before and after treatment.
Note: HER2 positive means that in the pathological detection/recheck of the primary or metastatic lesions performed by the pathology department, at least one tumor cell immunohistochemical staining intensity of 3+ or immunohistochemical staining intensity of 2+ and fluorescence in situ hybridization Technical [FISH] confirmed positive or NGS confirmed advanced colorectal cancer patients with HER2 gene amplification or mutation.
Full Information
NCT ID
NCT05350917
First Posted
February 17, 2022
Last Updated
May 16, 2022
Sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborators
BeiGene, Jiangsu Hengrui Pharmaceutical Co., Ltd., RemeGen Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05350917
Brief Title
Study of Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate in HER2-positive or Mutated Advanced Colorectal Cancer Who Failed Standard Therapy
Official Title
A Single-arm, Prospective, Open-label Clinical Study of Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate in HER2-positive or Mutated Advanced Colorectal Cancer Who Failed Standard Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 20, 2022 (Anticipated)
Primary Completion Date
June 20, 2025 (Anticipated)
Study Completion Date
June 20, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborators
BeiGene, Jiangsu Hengrui Pharmaceutical Co., Ltd., RemeGen Co., Ltd.
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 study will explore the efficacy and safety of tislelizumab (PD1 inhibitor) combined with DisitamabVedotin (ADC) and pyrotinib maleate (TKI) in the treatment of HER2-positive or mutated advanced colorectal cancer who have failed standard therapy .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive or Mutated Advanced Colorectal Cancer
Keywords
HER2-positive or Mutated, Advanced Colorectal Cancer, failure of standard treatment, Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate, PD-1 inhibitors+ADC+TKI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
A single-arm, prospective, open-label clinical study
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate
Arm Type
Experimental
Arm Description
One arm study
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
DisitamabVedotin, Pyrotinib maleate
Intervention Description
Tislelizumab: 200 mg, d1, intravenous infusion (ivgtt) administration, 21 days as a cycle.
DisitamabVedotin : 2mg/kg, d1, intravenous drip (ivgtt) administration, 21 days as a cycle.
Pyrotinib maleate tablets: 320 mg each time, Qd, orally administered within 30 minutes after breakfast, 21 days as a cycle.
Continuous administration until disease progression, death, toxicity intolerance, withdrawal of informed consent, or other reasons specified in the protocol; for patients who still benefit after comprehensive evaluation after initial disease progression, the investigator may decide whether to continue the treatment with the experimental drug .
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
It is defined as the number of subjects with the best response effect as complete remission (CR) or partial remission (PR) during the period from the start of the subjects receiving the treatment regimen of this study to the progression of the subjects' disease in the total number of subjects in the analysis data set. percentage of the population(%).
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR)
Description
Defined as the number of subjects whose tumors shrank or remained stable for a certain period of time from receiving the treatment regimen of this study to the progression of the subject's disease, including complete remission (CR) and partial remission (PR) in the analysis data set percentage of the total population(%).
Time Frame
Up to 24 months
Title
Progression Free Survival (PFS)
Description
Defined as the time from randomization to tumor progression in any aspect or death from any cause(Unit: month).
Assessed according to RECIST 1.1 criteria, analysis of this indicator included tumor evaluation results during study treatment and follow-up. If the patient has several indicators that can be judged as PD, the first indicator will be used for PFS analysis; recurrence, new lesions or death are considered to have reached the end of the study, and the patient is treated with other systemic or target-targeted anti-PD. Tumor treatment is also considered tumor progression.
Time Frame
Up to 24 months
Title
Overall survival (OS)
Description
Defined as the time from randomization to death from any cause(Unit: month).
Time Frame
Up to 24 months
Title
Drug-Related Safety Indicators
Description
Exposure to the investigational drug and incidence, nature, and severity of adverse events, including serious adverse events(n,%)。
Time Frame
Up to 24 months
Title
Study on the mechanism of drug resistance after progression
Description
Changes in HER2 status, HER2 gene, and HER2-related signaling pathways before and after treatment.
Note: HER2 positive means that in the pathological detection/recheck of the primary or metastatic lesions performed by the pathology department, at least one tumor cell immunohistochemical staining intensity of 3+ or immunohistochemical staining intensity of 2+ and fluorescence in situ hybridization Technical [FISH] confirmed positive or NGS confirmed advanced colorectal cancer patients with HER2 gene amplification or mutation.
Time Frame
Up to 24 months
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:
Colorectal cancer patients aged ≥18 years and ≤75 years old;
ECOG score 0~1 points;
Pathologically confirmed HER2 amplification-positive or mutated patients with advanced colorectal cancer who have failed or are intolerant of first-line therapy;
Note: HER2 amplification positive means that in the pathological detection/recheck of the primary tumor or metastases conducted by the pathology department of our hospital, at least one tumor cell immunohistochemical staining intensity is 3+ or immunohistochemical staining intensity is 2+ and has been Fluorescence in situ hybridization [FISH] confirmed positive or NGS confirmed advanced colorectal cancer patients with HER2 gene amplification or mutation.
According to RECIST1.1 criteria, there is at least one measurable target lesion, and tumor imaging evaluation is performed within 28 days before the first dose;
Expected survival time ≥ 12 weeks;
Major organ function is normal, that is, the following criteria are met:
The blood routine examination standards must meet: ANC ≥1.5×109/L; PLT ≥90×109/L; Hb ≥90g/L (no blood transfusion within 14 days);
Biochemical examinations should meet the following criteria: ALB≥30g/L; (no ALB transfusion within 14 days); TBIL≤Upper limit of normal (ULN); ALT and AST≤2.5 times upper limit of normal (ULN), if there is liver metastasis , then ALT and AST≤5ULN; alkaline phosphatase≤2.5 times the upper limit of normal (ULN); BUN and Cr≤1.5×ULN and creatinine clearance rate≥50 mL/min (CockcroftGault formula);
Cardiac ultrasound and echocardiography: left ventricular ejection fraction (LVEF≥50%);(4) QT interval (QTcF) corrected by Fridericia method of 18-lead ECG in females <470 ms;
For premenopausal or surgically sterilized female patients: consent to abstinence or use of effective contraception during treatment and for at least 7 months after the last dose of study treatment;
Voluntarily join the study and sign the informed consent
Exclusion Criteria:
Patients who have not received first-line standard therapy;
Previous antitumor therapy or radiation therapy for any other malignant tumor;
concurrently receiving anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy, and immunotherapy;
Has undergone major surgical procedures not related to colorectal cancer within 4 weeks prior to enrollment, or the patient has not fully recovered from such surgical procedures;
Serious heart disease or discomfort, including but not limited to the following:
Diagnosed history of heart failure or systolic dysfunction (LVEF < 50%)
High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate >100 bpm, significant ventricular arrhythmia (eg, ventricular tachycardia), or higher-grade AV block (ie, Mobitz II second-degree AV block or third-degree AV block)
Angina pectoris requiring antianginal drug treatment
Clinically significant heart valve disease
ECG showing transmural myocardial infarction
Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
Inability to swallow, bowel obstruction, or other factors that interfere with drug taking and absorption;
Known history of allergy to the drug components of this regimen; history of immunodeficiency, including HIV positive test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
Pregnant or lactating female patients, female patients of childbearing potential with a positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period and within 7 months after the last study drug;
have serious comorbidities or other comorbidities that would interfere with planned treatment, orAny other conditions for which the patient was deemed unsuitable for participation in this study by the investigator.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate in HER2-positive or Mutated Advanced Colorectal Cancer Who Failed Standard Therapy
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