Adebrelimab Combined With Induction Chemotherapy or SHR-8... | NCT07266025

NCT07266025

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm 1	Experimental	Participants assigned to arm 1 will receive neoadjuvant adebrelimab 1200 mg intravenously on day 1 combined with XELOX (capecitabine 1000 mg/m² orally twice daily on days 1-14 plus oxaliplatin 130 mg/m² intravenously on day 1) for one cycle, followed by adebrelimab monotherapy at the same dose and schedule for three additional cycles. Within 4-6 weeks after completion of the fourth cycle, curative-intent D2 radical gastrectomy will be performed. Post-operative adjuvant systemic therapy-regimen, duration, and number of cycles-will be left to the discretion of the treating investigator, guided by institutional standards and the patient's pathological and clinical status.	Drug: Adebrelimab Drug: XELOX Procedure: D2 radical gastrectomy
Arm 2	Experimental	Participants in arm 2 will receive neoadjuvant adebrelimab 1200 mg plus SHR-8068 280 mg administered intravenously on day 1 of a 21-day cycle for one cycle, followed by adebrelimab 1200 mg monotherapy on day 1 every 3 weeks for three additional cycles. Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle. Any post-operative adjuvant systemic treatment-including regimen, duration, and number of cycles-will be determined at the investigator's discretion according to institutional guidelines and the patient's pathological and clinical status.	Drug: Adebrelimab Drug: SHR-8068 Procedure: D2 radical gastrectomy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Adebrelimab	Drug	Participants in both arms will receive neoadjuvant adebrelimab 1200mg intravenously on day 1 of a 21-day cycle for four cycles.	Arm 1 Arm 2

Measure	Description	Time Frame
Pathological complete response (pCR) rate	The proportion of participants in whom no viable tumor cells remain in the primary tumor bed and regional lymph nodes (ypT0N0).	From randomization to the date of surgery, an average of 14 weeks.

Measure	Description	Time Frame
Major pathological response (MPR) rate	The proportion of participants in whom residual viable tumor cells constitute <10 % of the primary tumor bed in the resected surgical specimen.	From randomization to the date of surgery, an average of 14 weeks.
ypN stage

Eligibility Module

Eligibility Criteria

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