Clinical trial NCT05350917: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
Collaborators: name: BeiGene
name: Jiangsu Hengrui Pharmaceutical Co., Ltd.
name: RemeGen Co., Ltd.
First posted: 2022-04-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single-arm, prospective, open-label clinical study
Primary purpose: TREATMENT

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 .


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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 24 months
measure: Overall survival (OS)
timeFrame: Up to 24 months
measure: Drug-Related Safety Indicators
timeFrame: Up to 24 months
measure: Study on the mechanism of drug resistance after progression
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
References: