Known HER2-positive gastric cancer

Gastroesophageal junction (EGJ) cancer involving the proximal stomach with the tumor center located 642 cm from the EGJ

Peritoneal metastasis, positive peritoneal cytology (CY1P0), or retroperitoneal lymph node metastasis (No. 16a2/b1) or other distant metastases

Presence of unresectable factors, including unresectability due to tumor characteristics, surgical contraindications, or patient refusal of surgery

Prior or concurrent other malignancy, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast

Presence of any of the following cardiac clinical symptoms or diseases:

New York Heart Association (NYHA) class 652 heart failure or left ventricular ejection fraction (LVEF) 50% on color Doppler echocardiography

Unstable angina

Resting electrocardiogram (ECG) showing QTc 450 ms (male) or QTc 470 ms (female)

Resting ECG showing clinically significant abnormalities (e.g., abnormalities in heart rate, conduction, morphology), complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, or PR interval 250 ms

History of gastrointestinal perforation, intra-abdominal abscess, or intestinal obstruction within the past 3 months, or evidence of intestinal obstruction by imaging or clinical symptoms

Arterial/venous thrombotic events within 6 months before randomization, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, or pulmonary embolism

Known hereditary or acquired bleeding or thrombotic predisposition (e.g., hemophilia, coagulation disorders, thrombocytopenia)

Active peptic ulcer, unhealed wound, or bone fracture

Active infection requiring antimicrobial therapy (e.g., antibacterial, antiviral, or antifungal treatment)

Active hepatitis [hepatitis B: HBsAg positive and HBV DNA 500 IU/mL; hepatitis C: HCV antibody positive and HCV viral load  upper limit of normal]

Congenital or acquired immunodeficiency (e.g., HIV-infected patients)

Planned or prior organ or allogeneic bone marrow transplantation

Current interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia/ lung disease requiring steroid therapy, or other pulmonary conditions that may interfere with the assessment and management of immune-related lung toxicity, including pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonia or severe pulmonary dysfunction on screening CT scan

Active pulmonary tuberculosis

Any active autoimmune disease or history of autoimmune disease with potential for relapse [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients controlled with hormone replacement therapy alone are eligible)]

Known hypersensitivity to any study drug or excipient

Lactating women

Any other condition that, in the investigator's judgment, may affect the study results or necessitate premature termination of the study, such as alcohol or drug abuse, other serious diseases (including psychiatric disorders) requiring concomitant treatment, significant laboratory abnormalities, or family/social factors that could compromise patient safety