Gastric / Gastroesophageal Junction Adenocarcinoma, Mismatch Repair Deficient or MSI-High Solid Tumors, Immunotherapy
Conditions
Brief summary
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
DRUGInduction chemotherapy
Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2
PROCEDURED2 radical gastrectomy
Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.
DRUGImmunotherapy
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.
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of pathological complete response | 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
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response Rate | 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. |
| ypN stage | 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. |
| R0 resection rate | 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. |
| Event-free Survival | 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. |
| Overall Survival | 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. |
Contacts
Primary ContactZhaoqing Tang
Outcome results
None listed