Perioprative Study of IBI363 in Patients With MHC-II-Negative Locally Advanced Gastric Cancer

IBI363 Combined Chemotherapy for Perioperative Treatment of MHC-II-Negative Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: A Single-Center, Single-Arm Phase II Clinical Study

This is a phase 2 study designed to evaluate the safety and efficacy of IBI363 in combination with oxaliplatin and capecitabine (XELOX) or S-1 and oxaliplatin (SOX) in perioprative treatment of locally advanced MHC-II-negative gastric and gastroesophageal junction adenocarcinoma.

Key Inclusion Criteria:

1. Patients voluntarily enrolled in this study and signed informed consent forms;
2. Age 18-75 years;
3. Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma;
4. MHC-II negative, with <5% tumour cells displaying staining <2+ (grade 2 or stronger);
5. Clinically staged as cT3-4aN+M0 gastric or gastroesophageal junction adenocarcinoma confirmed by CT and/or laparoscopy (per AJCC 8th Edition staging);
6. No prior antineoplastic therapy for current disease (e.g., surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy);
7. Scheduled for surgical intervention following completion of neoadjuvant therapy;
8. Able to swallow tablets orally;
9. ECOG performance status 0-1;
10. Expected survival ≥6 months.

Key Exclusion Criteria:

1. Pregnant or lactating women, or women planning to become pregnant within 6 months prior to, during, or after the last dose of the investigational medicinal product.
2. Known signs of active bleeding from a lesion.
3. Patients with known dMMR/MSI-H status.
4. Oesophageal or pyloric near-obstruction affecting the subject's ability to eat or gastric emptying, or difficulty swallowing tablets.
5. Subjects with unresolved Grade >1 toxicity related to any prior antineoplastic therapy (excluding persistent Grade 2 alopecia, anaemia, peripheral neuropathy, electrolyte abnormalities correctable with treatment, or endocrine abnormalities controlled and stable with hormone replacement therapy).
6. Known dihydropyrimidine dehydrogenase (DPD) deficiency (or prior fluorouracil-containing therapy resulting in Grade 3 or higher mucositis).
7. Known hypersensitivity to any monoclonal antibody or component of the chemotherapy agents (capecitabine, oxaliplatin) (resulting in Grade 3 or higher hypersensitivity reaction).
8. History of epileptic seizures, active, newly diagnosed, or untreated central nervous system metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal metastases.
9. Clinically significant cardiovascular or cerebrovascular disease.