Perioperative IBI363 plus chemotherapy for MHC-II–negative locally advanced gastric and gastroesophageal junction adenocarcinoma

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

Tests whether adding the experimental drug IBI363 to standard perioperative chemotherapy helps adults (18–75) with MHC‑II–negative locally advanced gastric or gastroesophageal junction adenocarcinoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07325630 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center study gives patients IBI363 alongside standard perioperative chemotherapy regimens (XELOX or SOX) before and after planned surgery for cT3-4aN+M0 gastric or gastroesophageal junction adenocarcinoma. Eligible tumors must be MHC‑II negative by specified immunohistochemistry criteria and patients must be treatment‑naive with ECOG 0–1. The study will monitor safety, surgical outcomes, and measures of anti-tumor activity following neoadjuvant therapy and after surgery. All treatment and follow-up are conducted at Zhejiang Cancer Hospital in Hangzhou, China.

Who should consider this trial

Good fit: Adults 18–75 with pathologically confirmed, treatment‑naive cT3‑4aN+M0 gastric or gastroesophageal junction adenocarcinoma that is MHC‑II negative, with ECOG performance status 0–1 and planned for surgery, are ideal candidates.

Not a fit: Patients who are pregnant or lactating, have prior anti-cancer therapy for the current disease, have metastatic disease, poor performance status, or do not meet the MHC‑II‑negative biomarker criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding IBI363 could increase tumor shrinkage before surgery and improve long-term outcomes for this specific MHC‑II‑negative patient group.

How similar studies have performed: Combining immune‑oncology agents with perioperative chemotherapy has shown promise in gastric and GEJ cancers in other trials, but using IBI363 specifically and targeting MHC‑II‑negative tumors is a novel, not yet proven approach.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Xiangdong Cheng

Conditions: IBI363 + Chemotherapy