Chemotherapy Sequential Tislelizumab After Radical Resection in Patients With dMMR/MSI-H or POLE/POLD1 Mutations

NCT06118658 | Not Yet Recruiting Phase 2

• 1 other identifier: Adjuvant-GC/EGJ/CRC
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Objective of this study to evaluate 1-year disease-free survival in patients with dMMR/MSI-H or POLE/POLD1 gene mutations with gastric or esophagus-gastric junctional adenocarcinoma or colorectal adenocarcinoma after chemotherapy-sequential tiralizumab adjuvant radical resection (based on RECIST v1.1 criteria).

Conditions

Gastric; Colorectal Adenocarcinoma

Keywords

radical resection; adjuvant therapy; gastric; colorectal adenocarcinoma; esophagogastric junction adenocarcinoma; dMMR/MSI-H or POLE/POLD1 mutations

Outcome Measures

Primary Outcomes (1)

• 1-year disease-free survival based on RECIST v1.1 criteria (1-year DFS rate)

  The 1-year DFS rate was defined as the proportion of all subjects who did not have disease recurrence within 1 year from the start of randomization.

  1-year

Secondary Outcomes (5)

• 1-year MRD-negative survival assessed based on MRD testing

  1 year

• Disease-free survival (DFS)

  DFS is defined as the time from the start of randomization until a subject's disease recurrences or death from any cause, whichever occurs first

• overall survival (OS)

  OS is defined as the time from randomization to death from any cause

• time to local recurrence (TTLR)

  TTLR was defined as the time from randomization to local tumor recurrence.

• time to recurrence (TTR)

  TTR is defined as the time from randomization to tumor recurrence (including local recurrence and distant metastasis).

Other Outcomes (1)

• dMMR/MSI-H POLE/POLD1 gene mutation, TMB and its dynamic changes, and the relationship between efficacy and adverse reactions

  Subject recurrence of disease or discontinuation of treatment for any reason

Study Arms (1)

Chemotherapy-sequential tislelizumab adjuvant therapy

EXPERIMENTAL

About 30 patients who underwent radical gastrectomy or enterectomy with gastric adenocarcinoma or esophagogastric junction adenocarcinoma with postoperative pathological stage III or intestinal adenocarcinoma with postoperative pathological stage T1-3N2M0 or T4N+M0(American Joint Committee on Cancer,AJCC 8th Edition Cancer Stage) were scheduled to be enrolled after fully informed and signed informed consent Qualified subjects were selected to receive the standard XELOX or SOX regimen selected by the investigators according to the disease and postoperative pathology of the subjects for 4 cycles, followed by the sequential treatment of monotherapy tislelizumab (200mg,Q3W, IV infusion,4 cycles) starting from 4-6 weeks after surgery, with a maximum of 12 weeks Safety assessments such as ECOG physical examination of vital signs and laboratory tests will be performed regularly during treatment

Drug: tislelizumab

Interventions

tislelizumab DRUG

About 30 patients who underwent radical gastrectomy or enterectomy with gastric adenocarcinoma or esophagogastric junction adenocarcinoma with postoperative pathological stage III or intestinal adenocarcinoma with postoperative pathological stage T1-3N2M0 or T4N+M0(American Joint Committee on Cancer,AJCC 8th Edition Cancer Stage) were scheduled to be enrolled after fully informed and signed informed consent Qualified subjects were selected to receive the standard XELOX or SOX regimen selected by the investigators according to the disease and postoperative pathology of the subjects for 4 cycles, followed by the sequential treatment of monotherapy tislelizumab (200mg,Q3W, IV infusion,4 cycles) starting from 4-6 weeks after surgery, with a maximum of 12 weeks Safety assessments such as ECOG physical examination of vital signs and laboratory tests will be performed regularly during treatment

Chemotherapy-sequential tislelizumab adjuvant therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and voluntarily sign a written informed consent, which must be signed prior to performing the specified study procedure required for the study 2.Age and gender: ≥18 years old and≤75 years old, both men and women. 3.dMMR/MSI-H or POLE/POLD1 gene mutation was confirmed by immunohistochemical PCR or NGS 4.0-1 physical fitness score by the Eastern United States Cancer Collaboration (ECOG)。 5. Expected survival is 12 weeks 6.Radical gastrectomy or enterectomy, including open surgery or laparoscopic surgery, to achieve R0 resection (no residual cancer at the margin) 7.According to the American Joint Committee on Cancer AJCC 8th Edition cancer stage, it was confirmed by histopathology as gastric adenocarcinoma or esophagogastric junction adenocarcinoma or intestinal adenocarcinoma, and the postoperative pathological stage of gastric adenocarcinoma or esophagogastric junction adenocarcinoma was stage III; Patients with postoperative pathological stage of intestinal cancer T1-3N2M0 or T4N+M0 8.No metastasis or recurrence was determined based on images taken after surgery and within the first 28 days of randomization 9. Subjects are required to provide sufficient FFPE tumor tissue specimens or sections for relevant testing 10.The functions of important organs must meet the following requirements:
• Hematological system（No blood component or cell growth factor was used to support treatment within 7 days prior to the start of study therapy）:
• Neutrophil count≥1.5×10\^9/L; Platelet count≥100×10\^9/L; Hemoglobin≥90g/L;
• Liver function： Serum albumin≥28g/L; Total bilirubin (TBI)≤1.5×ULN; Alanine aminotransferase (ALT)≤3×ULN Aspartate aminotransferase (AST)≤2.5×ULN
• Renal function:
• Serum creatinine ≤1.5×ULN Calculated creatinine clearance≥50 mL/min (using the Cockcroft-Gault formula); Female: CrCl = (140- age in years) × weight in kg × 0.85 72 × serum creatinine in mg/ dL
• Male: CrCl = (140- age in years) × weight in kg × 1.00 72 × serum creatinine in mg/ dL
• Coagulation function:
• Subjects not receiving anticoagulation therapy: INR or APTT ≤ 1.5×ULN;
• Cardiac function: Left ventricular ejection fraction (LVEF)≥ 50 10. Fertile female subjects must undergo a urine or serum pregnancy test within 3 days prior to the first dosing (if the urine pregnancy test result is not confirmed negative, a serum pregnancy test is required, depending on the serum pregnancy result), and the result is negative If a fertile female subject has sex with an unsterilized male partner, the subject must use a highly effective contraceptive method since screening and must consent to continued use of the contraceptive method for 120 days after the last administration of the study drug; Whether to stop contraception after this time point should be discussed with the investigator 11.If an unsterilized male subject has sex with a fertile female partner, the subject must use an effective contraceptive method from the beginning of screening until the 120th day after the last dose; Whether to stop contraception after this time point should be discussed with the investigator.
• Subjects were willing and able to comply with the schedule for visiting treatment protocol laboratory tests and other study requirements.

You may not qualify if:

• Subjects with other malignancies in the 5 years prior to enrolment do not exclude subjects with other malignancies that have been cured by local treatment, such as basal or skin squamous cell carcinoma superficial bladder cancer cervix or breast carcinoma in situ
• Have received non-surgical treatment for gastric/esophagogastric junction/bowel cancer (e.g., radiotherapy, chemotherapy and hormone therapy)
• Liver peritoneum or distant metastasis
• Inability to take medications orally
• Unrelieved postoperative complications during screening (such as postoperative infection, suture rupture, gastrointestinal bleeding, pancreatic leakage, etc.)
• There are chemotherapy drugs contraindicated in this study and any group of adjuvant therapy regiments specified in the regimen cannot be accepted
• People with active autoimmune diseases that have required systemic treatment within the past two years (such as treatment with disease-modifying drugs, corticosteroids, immunosuppressants) and replacement therapy (such as insulin thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered a systemic treatment
• There is a pleural, pericardial or abdominal effusion that is clinically symptomatic, requires diuretic treatment and/or requires repeated drainage.
• There are active or recurrent inflammatory gastrointestinal diseases (such as Crohn's disease ulcerative colitis hemorrhagic enteritis chronic diarrhea, etc.)
• A history of myocarditis and cardiomyopathy with malignant arrhythmias.Unstable angina pectoris, myocardial infarction, congestive heart failure (grade 2 or higher according to the New York Heart Association Functional Scale), or vascular disease (such as an aortic aneurysm at risk of rupture) requiring hospitalization in the 12 months prior to initial administration,Or other heart damage that may affect the safety evaluation of the investigational drug (e.g., poorly controlled arrhythmias, myocardial ischemia)
• Medically difficult to control hypertension (systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥100mmHg) (based on an average of ≥2 measurements).
• Uncontrolled diabetes.
• Peripheral neuropathy ≥ grade 2.
• Severe infection within 4 weeks prior to initial dosing, including but not limited to comorbidized sepsis or severe pneumonia requiring hospitalization; Active infections that have received systemic anti-infective therapy within 2 weeks prior to initial dosing (excluding antiviral therapy for hepatitis B or C)
• Known active tuberculosis (TB), suspected active TB subjects need to undergo clinical examination to rule out; Known active syphilis infection

Sponsors & Collaborators

• China Medical University, China: lead

Study Sites (1)

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

Location

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: Chief physician

Model Details: About 30 patients who underwent radical gastrectomy or enterectomy with gastric adenocarcinoma or esophagogastric junction adenocarcinoma with postoperative pathological stage III or intestinal adenocarcinoma with postoperative pathological stage T1-3N2M0 or T4N+M0(American Joint Committee on Cancer,AJCC 8th Edition Cancer Stage) were scheduled to be enrolled after fully informed and signed informed consent Qualified subjects were selected to receive the standard XELOX or SOX regimen selected by the investigators according to the disease and postoperative pathology of the subjects for 4 cycles, followed by the sequential treatment of monotherapy tislelizumab (200mg,Q3W, IV infusion,4 cycles) starting from 4-6 weeks after surgery, with a maximum of 12 weeks Safety assessments such as ECOG physical examination of vital signs and laboratory tests will be performed regularly during treatment

Study Record Dates

• First Submitted: October 29, 2023
• First Posted: November 7, 2023
• Study Start: November 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)