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

Phase 2

Not yet recruiting

• Conditions: HER2-positive or Mutated Advanced Colorectal Cancer
• Interventions: Drug: Tislelizumab

• Registration Number: NCT05350917
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

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 .

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-17
• Study First Submitted QC: 2022-04-27
• Study First Posted: 2022-04-28
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17
• Study Start: 2022-06-20
• Primary Completion: 2025-06-20
• Study Completion: 2026-06-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tislelizumab Combined With DisitamabVedotin and Pyrotinib Maleate	Tislelizumab	One arm study

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 24 months	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

Name	Time	Method
Disease Control Rate (DCR)	Up to 24 months	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（%）.
Overall survival (OS)	Up to 24 months	Defined as the time from randomization to death from any cause（Unit: month）.
Progression Free Survival (PFS)	Up to 24 months	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.
Drug-Related Safety Indicators	Up to 24 months	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	Up to 24 months	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.