Factors Influencing Immunotherapy Response in Mismatch Repair Deficiency (dMMR) / Microsatellite Instability-High (MSI-H) Gastric/Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 主要终点
- Rate of pathological complete response
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
dMMR/MSI-H GC
Immunotherapy with induction chemotherapy
干预措施: Immunotherapy (Drug)
dMMR/MSI-H GC
Immunotherapy with induction chemotherapy
干预措施: Induction chemotherapy (Drug)
dMMR/MSI-H GC
Immunotherapy with induction chemotherapy
干预措施: D2 radical gastrectomy (Procedure)
结局指标
主要结局
Rate of pathological complete response
时间窗: 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).
次要结局
- Major Pathological Response Rate(From the initiation of treatment to the date of surgery, an average of 14 weeks.)
- ypN stage(From the initiation of treatment to the date of surgery, an average of 14 weeks.)
- R0 resection rate(From the initiation of treatment to the date of surgery, an average of 14 weeks.)
- Event-free Survival(The time from the initiation of treatment until disease progression, disease recurrence, death from any cause, or 3 years since enrollment.)
- Overall Survival(From the initiation of treatment until death from any cause or 3 years since enrollment.)
研究者
Xuefei.Wang
Chief of Department of Gastrointestinal Surgery
Shanghai Zhongshan Hospital