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

• Status: Not yet recruiting
• Trial end date: 2026-04-20
• Target enrollment: 0
• Participant gender: All

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 .

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University
• Collaborators: BeiGene; Jiangsu Hengrui Pharmaceutical Co., Ltd.; RemeGen Co., Ltd.
• Treatments: Maleic acid

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.