Biomarker Analysis of Tislelizumab Combined With Chemotherapy for Perioperative Treatment of G/GEJ Adenocarcinoma

NCT05508399 | Completed

• 1 other identifier: Gang Ji -2
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

G/GEJ adenocarcinoma is one of the most common malignant tumors in China, ranking the fifth highest incidence and third highest mortality worldwide. Currently, surgical resection is the preferred treatment for G/GEJ adenocarcinoma, while the 5-year survival rate of patients is lower than 25%. Compared with surgical resection, immunotherapy is proved to be able to effectively prolong the survival time of patients. On one hand, with the continuous promotion of immunotherapy drugs, the exploration of neoadjuvant application of immunotherapy in G/GEJ adenocarcinoma has become a hotspot in recent years. It's also on their way that clinical trials of programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1) and other immune checkpoints are carried out. On the other hand, the research found that although the curative effect of immune therapy seems better, the present G/GEJ adenocarcinoma immunotherapy marker researches mainly focused on the late stage of the cancer, with few studies of immune markers of neoadjuvant therapy for G/GEJ adenocarcinoma. Additionally, it's not quite feasible for single biomarkers to predict the immune treatment effect precisely. Therefore, combined with clinicopathology and therapeutic effects, this study is aimed to construct the efficacy prediction model of anti-PD-1 antibody together with chemotherapy for G/GEJ adenocarcinoma, by detecting RNA expression. Furthermore, this study will perform drug sensitivity test and bio-molecular test on patient derived organoid model to validate the biomarkers found from biological specimens.

Conditions

Locally Advanced Gastric Adenocarcinoma; PD-1

Outcome Measures

Primary Outcomes (2)

• Relative RNA biomarkers

  At the RNA level, to identify the biomarkers related to the efficacy of neoadjuvant therapy with PD-1 mab combined with chemotherapy in locally advanced gastric cancer.

  From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Prediction model for efficacy

  A prediction model for the efficacy of PD-1 mab combined with chemotherapy, constructed on the basis of clinical pathology, gene variation, gene expression and other factors.

  From the date of completing collecting data, to the date of death from any cause or the end date of the whole trail, whichever came first, assessed up to 2 years

Secondary Outcomes (3)

• Conditions of immune microenvironment

  From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Drug resistance mechanism

  From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• Response of organoids to the same neoadjuvant drugs as the corresponding patients

  From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Study Arms (1)

PD-1 group

Patients who are qualified for receiving anti-PD-1 antibody combined with chemotherapy neoadjuvant therapy

Other: DNA panel and RNA Sequencing

Interventions

DNA panel and RNA Sequencing OTHER

Interventions include collecting samples, DNA panel test and full transcriptome sequencing. Before collecting samples, obtaining written informed consent from patient in advance. 1. Blood cell samples; 2. Paraffin sample of residual tumor tissue of biopsy; 3. Paraffin sample of residual tumor tissue and paracancer tissue after gastrectomy.

PD-1 group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with G/GEJ adenocarcinoma who are ready to receive PD-1 monoclonal antibody combined with chemotherapy neoadjuvant treatment.

You may qualify if:

• Aged 18-80 (including 18 and 80);
• G/GEJ adenocarcinoma confirmed by basic ultrasound gastroscopy, enhanced CT (PET/CT), MRI or diagnostic laparoscopy;
• Biopsy histologically confirmed adenocarcinoma
• As assessed by the investigator, patients who are qualified for receiving PD-1 mab combined with chemotherapy neoadjuvant therapy;
• Patients who volunteer to participate in this study and sign the informed consent, with good compliance and cooperation in the acquisition of biological specimens.

You may not qualify if:

• Patients whose biological specimens do not meet the detection standards;
• In the judgment of the investigator, the patients with factors that might have caused the study to be terminated.

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Xijing Hospital of Digestive Diseases

Xi'an, Shaanxi, 710000, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biological samples of DNA will be collected before and after neoadjuvant treatment with PD-1 mab combined with chemotherapy, then they will be used to detect and analyze the variation in DNA. Biological samples of RNA detection will be used to analyze the expression profile. Combined with clinicopathological features, clinical treatment efficacy and prognosis, samples of DNA and RNA will be used to analyze biomarkers and construct models for predicting efficacy of PD-1 mab combined with chemotherapy in locally advanced gastric cancer. Meanwhile, the investigators are going to establish organoids with immune microenvironment from surgically resected tumor tissues of G/GEJ adenocarcinoma patients. Organoids will be treated with the same immune-chemotherapy drugs with the corresponding patients who accepted neoadjuvant therapy.

MeSH Terms

Interventions

Sequence Analysis, RNA

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 19, 2022
• Study Start: July 18, 2022
• Primary Completion: January 10, 2024
• Study Completion: October 10, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-03

Locations

CN (1)