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Not yet recruiting NCT07259473

Factors Influencing Immunotherapy Response in dMMR/MSI-H Gastric/Gastroesophageal Junction Adenocarcinoma

Phase II Interventional Gastric / Gastroesophageal Junction Adenocarcinoma Mismatch Repair Deficient or MSI-High Solid Tumors Immunotherapy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Immunotherapy, Induction chemotherapy, D2 radical gastrectomy.
Who it may be relevant to
Registry conditions: Gastric / Gastroesophageal Junction Adenocarcinoma, Mismatch Repair Deficient or MSI-High Solid Tumors, Immunotherapy. Basic parameters: 18 years — 85 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Center list to be confirmed — check the primary protocol.
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Factors Influencing Immunotherapy Response in Mismatch Repair Deficiency (dMMR) / Microsatellite Instability-High (MSI-H) Gastric/Gastroesophageal Junction Adenocarcinoma

Overview

dMMR/MSI-H is a key molecular subtype of gastric cancer, found in 8-22% of cases. It is typically associated with older age, female sex, distal tumor location, and intestinal histology (Lauren classification). While this subtype predicts better survival in locally advanced disease, its prognostic role in metastatic settings is less clear. Notably, dMMR/MSI-H tumors are often resistant to conventional chemotherapy. Conversely, they demonstrate exceptional sensitivity to immunotherapy. This has led to effective strategies using immune checkpoint inhibitors, either alone or combined with chemotherapy, in both neoadjuvant and advanced disease settings. However, key challenges remain. Prospective data are largely from Western populations, leaving the efficacy in Asian patients-who bear a high disease burden-less defined. Furthermore, about half of dMMR/MSI-H patients exhibit primary or acquired resistance to immunotherapy. A deeper understanding of the tumor-immune dynamics during treatment is crucial to uncover resistance mechanisms and improve patient outcomes.

Interventions

  • Drug Immunotherapy
    Drug: Immune checkpoint inhibitors (ICIs), specifically PD-1 antibodies, PD-L1 antibodies, PD-1/CTLA-4 bispecific antibodies, or PD-1/CTLA-4 combination therapy. Regimen: 4 treatment cycles.
  • Drug Induction chemotherapy
    Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2
  • Procedure D2 radical gastrectomy
    Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.

Primary outcome measures

  • Rate of pathological complete response [Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.]
Secondary outcome measures (5)
  • Major Pathological Response Rate [Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.]
  • ypN stage [Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.]
  • R0 resection rate [Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.]
  • Event-free Survival [Time frame: The time from the initiation of treatment until disease progression, disease recurrence, death from any cause, or 3 years since enrollment.]
  • Overall Survival [Time frame: From the initiation of treatment until death from any cause or 3 years since enrollment.]

Eligibility criteria

Inclusion criteria

  • Male or female, aged 18 to 85 years.
  • Histologically confirmed gastric cancer or adenocarcinoma of the esophagogastric junction (only Siewert types II and III are included).
  • dMMR status confirmed by immunohistochemistry (IHC) or MSI-H status confirmed by PCR/NGS.
  • Tumor clinical staging meeting the following criteria:

cT≥2, any N, M0, assessed by the investigator as potentially resectable and planned for preoperative treatment followed by surgery.

  • Willing to receive treatment with immune checkpoint inhibitors (including, but not limited to, various PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors, PD-1/CTLA-4 bispecific antibodies, etc.), which may be combined with or without standard chemotherapy regimens for gastric cancer.

Exclusion criteria

  • Tumor histology other than adenocarcinoma, such as squamous cell carcinoma, neuroendocrine carcinoma, etc.
  • Presence of central nervous system metastases and/or leptomeningeal carcinomatosis.
  • Prior antitumor therapy directed at the current gastric cancer (excluding palliative gastrointestinal bypass surgery performed to relieve obstructive symptoms).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07259473 · B2025-541R

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗