Inclusion Criteria:
- Male or female, age ≥ 18 years
- Pathologically confirmed gastric or gastro-oesophageal-junction adenocarcinoma (Siewert II and III only)
- dMMR confirmed by IHC or MSI-H confirmed by PCR
- Investigator-assessed potentially curative resection feasible before study entry
- CT or MRI clinical stage cT ≥ 2 N any M0 per AJCC 8th edition; laparoscopy with peritoneal washing cytology (and peritoneal biopsy if indicated) recommended to exclude peritoneal metastasis
- ECOG performance status 0-2
- Able to swallow tablets
- Expected survival ≥ 6 months
- Laboratory values within 7 days before randomisation:
ANC > 1.5 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 75 × 10⁹/L Serum creatinine ≤ 1.5 × ULN or eGFR ≥ 60 mL/min/1.73 m² ALT and AST ≤ 2.5 × ULN; total bilirubin ≤ 1.5 × ULN (or TBIL > 1.5 × ULN with direct bilirubin ≤ ULN); albumin ≥ 25 g/L INR or PT ≤ 1.5 × ULN and aPTT ≤ 1.5 × ULN (or on anticoagulation within therapeutic range)
- Signed written informed consent; able to comply with protocol visits, treatment, labs, biospecimen collection
- WOCBP must have negative serum pregnancy test within 72 h before randomisation, not breastfeeding, and use highly effective contraception from screening until 2 months after last adebrelimab/SHR-8068 or 6 months after last chemotherapy, whichever is longer
- Men with pregnant partners or WOCBP partners must be surgically sterile or use highly effective contraception during study and for same post-treatment periods; no sperm donation allowed
Exclusion Criteria:
- Tumour histology squamous-cell, neuro-endocrine, or other non-adenocarcinoma types
- Unresectable disease (tumour-related or surgical contraindication) or subject refuses surgery
- Tumour requiring transthoracic surgical approach
- CNS metastases and/or carcinomatous meningitis
- Prior anti-gastric-cancer therapy (surgery, radiotherapy, chemotherapy, targeted, immunotherapy) except bypass for obstruction
- Previous malignancy or concurrent malignancy except completely excised basal/squamous skin cancer, superficial bladder cancer, or in-situ prostate/cervix/breast cancer disease-free ≥ 5 years
- Cardiac conditions:
NYHA class > II or LVEF < 50 % on echo Unstable angina MI within 1 year Resting QTc > 450 ms (M) or > 470 ms (F) Clinically significant ECG abnormalities, complete LBBB, 3rd-degree AV block, 2nd-degree AV block, PR > 250 ms Risk factors for QT prolongation (HF, hypokalaemia, congenital long-QT syndrome, family history of long QT or sudden death < 40 y, concomitant QT-prolonging drugs)
- History of GI perforation, intra-abdominal abscess, or bowel obstruction within 3 months or imaging/clinical signs of obstruction
- Clinically significant bleeding or bleeding diathesis within 3 months (e.g. GI bleeding, haemorrhagic gastritis, vasculitis); positive faecal occult blood must be endoscopically cleared if still positive on repeat testing (unless gastroscopy within 3 months shows no lesion)
- Arterial or venous thrombo-embolic event within 6 months (stroke, TIA, intracranial haemorrhage, cerebral infarction)
- Hypersensitivity to any study-drug component
- Severe hypersensitivity history to any monoclonal antibody
- Pregnant or lactating women
- Positive HIV antibody
- Active hepatitis (HBsAg positive with HBV DNA ≥ 500 IU/mL; HCV antibody positive with HCV RNA > ULN)
- Prior therapy targeting CTLA-4/PD-1/PD-L1 or other T-cell co-stimulatory/immune-checkpoint pathways (including therapeutic vaccines)
- Active autoimmune disease or autoimmune disease with relapse risk within 2 years (except stable hypothyroidism on replacement or well-controlled type 1 diabetes on insulin)
- History of idiopathic pulmonary fibrosis, drug-related pneumonia, organising pneumonia (BOOP/COP), or CT evidence of active pneumonia at screening
- Live attenuated vaccine within 4 weeks before first study dose or expected need during study
- Immunodeficiency disorder or chronic systemic corticosteroids or other immunosuppressive therapy within 7 days before first dose (includes prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-TNF agents)
- Any condition that, in the investigator's opinion, increases study risk, interferes with protocol conduct, or compromises informed consent or compliance