Study of Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate in HER2-positive or Mutated Advanced Colorectal Cancer Who Failed Standard Therapy

NCT ID: NCT05350917

Last Updated: 2022-05-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-20
• Study Completion Date: 2026-06-20

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 .

Conditions

HER2-positive or Mutated Advanced Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate

One arm study

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

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 .

Interventions

Tislelizumab

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 .

Intervention Type: DRUG

Other Intervention Names

DisitamabVedotin; Pyrotinib maleate

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:

1. 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);

2. 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);

3. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: collaborator

Jiangsu Hengrui Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: lead

Responsible Party

Hong Zong

Department of Oncology, The First Affiliated Hospital of Zhengzhou University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

RCVDTYPEC024

Identifier Type: -

Identifier Source: org_study_id