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

NCT05350917 | Not Yet Recruiting Phase 2

• 1 other identifier: RCVDTYPEC024
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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

Keywords

HER2-positive or Mutated; Advanced Colorectal Cancer; failure of standard treatment; Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate; PD-1 inhibitors+ADC+TKI

Outcome Measures

Primary Outcomes (1)

• 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（%）.

  Up to 24 months

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  Up to 24 months

• Progression Free Survival (PFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

• Drug-Related Safety Indicators

  Up to 24 months

• Study on the mechanism of drug resistance after progression

  Up to 24 months

Study Arms (1)

Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate

EXPERIMENTAL

One arm study

Drug: Tislelizumab

Interventions

Tislelizumab 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 .

Also known as: DisitamabVedotin, Pyrotinib maleate

Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead
• BeiGene: collaborator
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator
• RemeGen Co., Ltd.: collaborator

MeSH Terms

Interventions

tislelizumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Oncology, The First Affiliated Hospital of Zhengzhou University

Model Details: A single-arm, prospective, open-label clinical study

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: April 28, 2022
• Study Start: June 20, 2022
• Primary Completion: June 20, 2025
• Study Completion: June 20, 2026
• Last Updated: May 17, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share