Predicting immunotherapy response in gastric cancer using tumor immune cells and H3K4me3

The Construction of a Predictive Model for Gastric Cancer Immunotherapy Response Based on Tumor-Infiltrating Lymphocytes (TILs) and Histone H3K4me3 in the Tumor Microenvironment

This project will test whether the number, location of tumor-infiltrating lymphocytes and levels of histone H3K4me3 in tumor tissue can help predict how well first-line immunotherapy plus chemotherapy works for people with advanced gastric or gastroesophageal junction cancer.

Quick facts

• Study type: Observational
• Enrollment: 170 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changzhi People's Hospital Affiliated to Changzhi Medical College (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Changzhi, Shanxi)
• Trial ID: NCT07069842 on ClinicalTrials.gov

What this trial studies

This observational study will collect tumor tissue and clinical outcome data from adults with locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma who are starting first-line immune checkpoint inhibitors plus chemotherapy. Researchers will measure the density and spatial distribution of tumor-infiltrating lymphocytes and the level of H3K4me3 modification using multiplex immunofluorescence, immunohistochemistry, Co-IP, and in situ hybridization. Those molecular and spatial features will be correlated with treatment response by iRECIST and other clinical endpoints to construct a predictive model. The goal is to identify biomarker patterns in the tumor microenvironment that distinguish responders from non-responders.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed locally advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma, ECOG 0–2, at least one measurable lesion, and planned first-line immune checkpoint inhibitor plus chemotherapy (with or without anti-HER2 therapy).

Not a fit: Patients with recent secondary malignancies, brain or meningeal metastases, serious comorbidities that preclude safe participation, or who do not receive first-line ICIs plus chemotherapy are unlikely to be included or benefit from this predictive model.

Why it matters

Potential benefit: If successful, the model could help clinicians choose immunotherapy for patients more likely to benefit and avoid ineffective treatment for others.

How similar studies have performed: Prior work has shown that TIL patterns often correlate with immunotherapy outcomes, while incorporating H3K4me3 epigenetic marks into a clinical predictive model for gastric cancer remains relatively novel with limited prior validation.

Eligibility criteria

Inclusion Criteria:

* 1.Diagnosed with histologically confirmed locally advanced (LA) unresectable or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, aged 18 to 75 years.

  2.Scheduled to receive first-line therapy with ICIs plus chemotherapy with or without anti-her-2 therapy.

  3.Have at least one measurable lesion as the target lesion per iRECIST V.1.1 criteria and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

\- 1.History of secondary malignant tumors within 3 years prior to study initiation, or other types of brain/meningeal metastatic tumors.

2.Presence of concomitant diseases that, in the investigator's judgment, may seriously jeopardize their safety or interfere with study completion

Where this trial is running

Changzhi, Shanxi

• Changzhi People's Hospital — Changzhi, Shanxi, China (Recruiting)

Study contacts

• Study coordinator: Wenqing Hu

Conditions Gastric Cancer; Immunotherapy