Triple attack on stomach cancer: radiation, chemo, and a smart antibody

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Male or female participants aged 18 to 75 years. 2. Histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma. 3. Unresectable locally advanced or metastatic gastric cancer, with primary and metastatic lesions amenable to radiotherapy (excluding patients with brain metastases or extensive metastatic disease). 4. HER2-negative disease. 5. ECOG performance status of 0-1. 6. At least one measurable lesion according to RECIST version 1.1. 7. Adequate organ function, including: * Hemoglobin ≥90 g/L; * White blood cell count ≥3.5 × 10⁹/L; * Absolute neutrophil count ≥1.5 × 10⁹/L; * Platelet count ≥100 × 10⁹/L; * Serum creatinine ≤1.0 × upper limit of normal (ULN); * Blood urea nitrogen (BUN) ≤1.0 × ULN; * Alanine aminotransferase (ALT) ≤1.5 × ULN; * Aspartate aminotransferase (AST) ≤1.5 × ULN; * Alkaline phosphatase (ALP) ≤1.5 × ULN; * Total bilirubin (TBIL) ≤1.5 × ULN; * Negative urine protein; * Normal coagulation function. 8. No contraindications to immunotherapy. 9. No history of hypersensitivity to fluoropyrimidines or platinum-based agents. 10. No prior surgery, chemotherapy, immunotherapy, or other antitumor therapy for gastric or gastroesophageal junction cancer since diagnosis. 11. No previous radiotherapy to the intended irradiation sites. 12. Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: 1. Brain metastases or extensive metastatic disease. 2. Prior treatment with PD-1, PD-L1, TGF-β, CTLA-4 inhibitors, or other investigational immunotherapies. 3. Severe autoimmune diseases, including but not limited to active inflammatory bowel disease (Crohn's disease or ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, or autoimmune vasculitis (e.g., Wegener's granulomatosis). 4. Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis. 5. Conditions associated with an increased risk of gastrointestinal perforation, including active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors. 6. History of another malignancy, except adequately treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or carcinoma in situ of the cervix. 7. Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable cardiac arrhythmia. 8. Any physical examination findings, laboratory abnormalities, or uncontrolled medical conditions that, in the investigator's judgment, may interfere with study outcomes or increase the risk of treatment-related complications. 9. Pregnant or breastfeeding women. 10. Congenital or acquired immunodeficiency, including HIV infection, or a history of organ transplantation or allogeneic hematopoietic stem cell transplantation. 11. Active hepatitis B infection (HBV DNA ≥2,000 IU/mL), active hepatitis C infection, or active tuberculosis. 12. Receipt of any live or other prohibited vaccines within 4 weeks before study treatment. Seasonal inactivated influenza vaccines are permitted, whereas intranasal live attenuated influenza vaccines are not permitted. 13. Concurrent treatment with other immunosuppressive agents, chemotherapy, investigational drugs, or long-term systemic corticosteroids. 14. Psychiatric disorders, substance abuse, or social conditions that may compromise treatment compliance, as determined by the investigator. 15. Known hypersensitivity or contraindication to any study treatment.