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NCT Number: NCT07259473

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

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.

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Key information

Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma Immunotherapy Mismatch Repair Deficient or MSI-High Solid Tumors Turcot syndrome

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Immunotherapy

Drug

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.

Induction chemotherapy

Drug

Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m^2

D2 radical gastrectomy

Procedure

Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.

Primary outcomes

  1. Rate of pathological complete response

    Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.

    The proportion of subjects exhibiting no residual tumor cells in the surgical specimen and the absence of positive lymph nodes (i.e., a pathological stage of ypT0N0).

Secondary outcomes

  1. Major Pathological Response Rate

    Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.

    The proportion of subjects with residual viable tumor cells accounting for <10% of the surgical specimen from the primary tumor site.

  2. ypN stage

    Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.

    Lymph-node status after neoadjuvant therapy (ypN stage) will be assessed according to the American Joint Committee on Cancer (AJCC) 8th edition staging system.

  3. R0 resection rate

    Time frame: From the initiation of treatment to the date of surgery, an average of 14 weeks.

    The proportion of patients who undergo surgery with microscopically negative resection margins.

  4. 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.

    The time from the subject's enrollment until disease progression, disease recurrence, or death from any cause.

  5. Overall Survival

    Time frame: From the initiation of treatment until death from any cause or 3 years since enrollment.

    The time from the subject's enrollment until death from any cause.

Study contacts

Contact information is provided by the study sponsor or research team.

Zhaoqing Tang

CONTACT

[email protected]

021-64041990

Sponsors and collaborators

Lead sponsor

Shanghai Zhongshan Hospital

Other

Registry information

Official study title

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

Acronym: Pre-CATALIS

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Dec 2, 2025
Registry last updated
Jan 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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