Tislelizumab Combined With Neoadjuvant Chemotherapy Used in the Perioperative Treatment.

A Multicenter, Prospective Phase II Clinical Study of Tislelizumab in Combination With Chemotherapy for the Perioperative Treatment of Resectable Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma

To evaluate the efficacy of Tislelizumab in combination with chemotherapy versus chemotherapy in neoadjuvant treatment of patients with MHC-II positive (IHC≥2+) and locally advanced gastric/gastroesophageal junction adenocarcinoma by evaluating the main pathologic response rate (MPR).

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: SOX/XELOX

Detailed Description

This study is a multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of Tislelizumab combined with chemotherapy in the perioperative treatment of resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.

A study aimed at untreated gastric and gastroesophageal junction adenocarcinoma patients with resectable locally advanced cT3~4aN+M0 or cT4bNanyM0 (according to AJCC 8th edition staging) The study aimed to enroll 134 untreated resectable locally advanced gastric adenocarcinoma and gastroesophageal junction adenocarcinoma patients, with the primary pathological response rate (MPR) as the primary endpoint.

The subjects need to undergo a screening period examination within 21 days before randomization to determine whether they meet the study conditions. Subjects who meet the research criteria will be randomly divided into MHC - Ⅱ positive group (IHC ≥ 2+) and MHC - Ⅱ negative group (IHC 0/1+) based on their MHC - Ⅱ expression. The MHC - Ⅱ positive group (IHC ≥ 2+) will be randomly divided into two groups in a 1:1 ratio, receiving either Tislelizumab combined with chemotherapy (Group A) or chemotherapy (Group B). The MHC - Ⅱ negative group (IHC 0/1+) will be randomly divided into two groups in a 1:1 ratio, receiving either Tislelizumab combined with chemotherapy (Group C) or chemotherapy (Group D). Randomly stratified factors include Lauren classification (intestinal type vs. diffuse type vs. mixed type).

Based on the sample size assumption of this study, the proportion of MHC - Ⅱ positive population in this study should reach at least 50%.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiangdong Cheng; Phone Number: 13968032995; Email: chengxd@zjcc.org.cn
• Study Contact Backup: Name: Can Hu; Phone Number: 15168376735; Email: hucanchina@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient voluntarily joined this study and signed an informed consent form;
• Age ≥ 18 years old, ≤ 75 years old
• Pathological diagnosis of gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction
• Patients must be able to provide fresh slices of tumor tissue (FFPE tissue blocks or approximately 15 slides), unstained FFPE slides, and if clinically feasible, fresh biopsy samples will be preferred. If archived samples cannot be obtained, fresh tumor biopsy specimens must be collected during the baseline period, with the same requirements for glass slides as archived tumor tissue
• Clinical staging determined by CT and laparoscopy for curative resection is cT3~4aN+M0 or cT4bNanyM0 for gastric and gastroesophageal junction adenocarcinoma patients (according to AJCC 8th edition staging)
• Have not received anti-tumor treatment (such as surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.)
• Plan to undergo surgical treatment after the completion of neoadjuvant therapy
• Able to swallow pills normally
• ECOG score 0-1 points
• Expected survival time ≥ 12 months
• Normal function of major organs, i.e. meeting the following criteria:The standard for blood routine examination must comply with: (No blood transfusion or blood products within 14 days, no correction using G-CSF or other hematopoietic stimulating factors)，Neutrophil absolute count ≥ 1.5 × 109/L; Platelets ≥ 80 × 109/L; Hemoglobin ≥ 80g/L

• Biochemical examination must meet the following standards: Total bilirubin<1.5

  • ULN; ALT and AST ≤ 2.5 × ULN; Serum Cr ≤ 1.5 x ULN or endogenous creatinine clearance rate>50ml/min (male: endogenous creatinine clearance rate=(140 age) x body weight)/(72 x serum Cr); Female: Endogenous creatinine clearance rate=(140 age) x body weight/(72 x serum Cr) x 0.85; Weight unit: kg; Serum Cr unit: mg/mL
• Female subjects with pregnancy ability must undergo a serum pregnancy test within 7 days before the first medication, and the result is negative. They are willing to use efficient contraception methods during the trial period and 120 days after the last dose. For male subjects whose partners are women of childbearing age, surgical sterilization or agreement to use efficient methods of contraception during the trial period and 120 days after the last dose should be considered

Exclusion Criteria:

• There are non resectable factors, including tumor reasons that cannot be resected or surgical contraindications that cannot be resected or those who refuse surgery
• Previously or currently suffering from other malignant tumors
• Suffering from any chronic or major illness that is considered intolerable to treatment (such as severe heart disease, uncontrolled hypertension, certain degrees of liver and kidney dysfunction, etc.)
• Those who have experienced gastrointestinal perforation, abdominal abscess in the past, or recent (within 3 months) intestinal obstruction or imaging and clinical symptoms indicating accompanying intestinal obstruction
• If there are significant clinically significant bleeding symptoms or clear bleeding tendencies, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis, within the first 3 months prior to the first use of the study drug, and if fecal occult blood is positive during the baseline period, a follow-up examination can be conducted. If the results are still positive after the follow- up examination, a gastroscopy examination is required (excluding those who have undergone gastroscopy examination within 3 months prior to enrollment to exclude such situations)
• If the patient is in the active infection stage and needs treatment (such as using antibiotics, antiviral drugs, or antifungal drugs)
• Active hepatitis (hepatitis B reference: HBsAg positive and HBV DNA ≥ 500 IU/ml; hepatitis C reference: HCV antibody positive and HCV copy number>upper limit of normal value)
• Patients with congenital or acquired immune dysfunction (such as HIV infected individuals)
• Patients with any active autoimmune diseases or a history of autoimmune diseases with the possibility of recurrence
• Planned or previously received organ or allogeneic bone marrow transplantation
• Subjects who currently have interstitial pneumonia or interstitial lung disease, or have a history of requiring hormone therapy for interstitial pneumonia or interstitial lung disease, or those whose screening period CT shows active pneumonia or severe lung function impairment; Active pulmonary tuberculosis
• Current or recent use of immunosuppressive drugs or systemic corticosteroids for the purpose of achieving immunosuppression
• Patients who have received attenuated live vaccines within 28 days prior to the first use of the study drug, or who need to receive such vaccines during treatment or within 60 days after the last dose
• Known to be allergic to any investigational drug or excipient
• Lactating women
• Any factors determined by the researcher that may affect patient safety and result in the forced termination of this study midway

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (MHC-II positive with Tislelizumab and SOX/XELOX); Preoperative treatment with Tislelizumab and SOX/XELOX for MHC-II positive patient.	Drug: Tislelizumab; Preoperative treatment with Tislelizumab; Drug: SOX/XELOX; Preoperative treatment with SOX/XELOX
Active Comparator: B (MHC-II positive with SOX/XELOX); Preoperative treatment with SOX/XELOX for MHC-II positive patient.	Drug: SOX/XELOX; Preoperative treatment with SOX/XELOX
Experimental: C (MHC-II negative with Tislelizumab and SOX/XELOX); Preoperative treatment with Tislelizumab and SOX/XELOX for MHC-II negative patient.	Drug: Tislelizumab; Preoperative treatment with Tislelizumab; Drug: SOX/XELOX; Preoperative treatment with SOX/XELOX
Active Comparator: D (MHC-II negative with SOX/XELOX); Preoperative treatment with SOX/XELOX for MHC-II negative patient.	Drug: SOX/XELOX; Preoperative treatment with SOX/XELOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRP (Main pathological response)	The percentage of subjects who showed no residual tumor cells (including lymph nodes, stage ypT0N0M0) and only residual single or small focal cancer cells under the light microscope	After operation about 2 weeks until postoperative pathology report come out.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR (pathologic complete response)	The percentage of subjects with a TRG grade of 0 who do not have live tumor cell residues in the primary tumor lesion	After operation about 2 weeks until postoperative pathology report come out.
DFS (Disease free survival)	Refers to the time between the time of baseline imaging evaluation and disease recurrence or death (whichever occurs first) in disease-free subjects after surgery.	From date of randomization until the date of first documented progression， assessed up to 100 months
OS (Overall survival)	The time between the date of enrollment and death from any cause	From date of randomization until the date of death, assessed up to 120 months

Collaborators and Investigators

• Sponsor: Xiangdong Cheng
• Collaborators: Shanxi Province Cancer Hospital; The Second Affiliated Hospital of Harbin Medical University; Liaoning Tumor Hospital & Institute; Sichuan Cancer Hospital and Research Institute
• Investigators: Study Chair: Xiangdong Cheng, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 25, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: IRB-2024-311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No