Cadonilimab Combination Regimen as First-line Treatment for HER2-expressing GC/GEJ Patients

Inclusion Criteria: \- 1.Sign the informed consent form. 2. ≥18 years and ≤75 years . 3.Histologically confirmed unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (tumor center located within 5 cm proximally or distally from the esophagogastric junction according to the Siewert classification system). 4.Confirmed PD-L1 expression status (accepts PD-L1 expression test results confirmed by the investigator). 5.HER2 expression (accepts HER2 expression test results confirmed by the investigator): * Cohort 1 and Cohort 2: HER2-positive defined as IHC 3+, or IHC 2+ and ISH or FISH positive. ISH positivity is defined as a HER2 gene copy number to CEP17 copy number ratio ≥2.0; if the ratio is \<2.0 but the HER2 gene copy number \>6, it is also considered ISH positive. * Cohort 3: HER2 low expression, defined as IHC 1+ or IHC 2+ but ISH or FISH negative. 6.No prior systemic anti-tumor therapy. 7.With at least one measurable lesion (RECIST 1.1 criteria) in the subject . 8.Expected survival ≥ 3 months. 9.ECOG 0/1. 10.Adequate organ function is determined by the following criteria: 1. Hematological (no transfusions or growth factor support allowed within 7 days before the first dose):Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (1,500/mm³); Platelet count ≥ 100 × 10\^9/L (100,000/mm³);Hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L. 2. Liver:Serum albumin ≥ 28 g/L (no albumin infusions allowed within 14 days before the first dose);Total bilirubin (TBil) ≤ 1.5 × ULN; for subjects with liver metastases or evidence/suspicion of Gilbert's disease, TBil ≤ 3 × ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for subjects with liver metastases, AST and ALT ≤ 5 × ULN. 3. Renal:Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula);Urinalysis: urine protein \< 2+; if urine protein ≥ 2+, then 24-hour urine protein ≤ 1 g. 4. Coagulation:International normalized ratio (INR) ≤ 1.5 × ULNActivated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;Prothrombin time (PT) ≤ 1.5 × ULN. 5. Cardiac function:New York Heart Association (NYHA) class \< III;Left ventricular ejection fraction (LVEF) ≥ 50%. 11.For premenopausal women, a negative serum pregnancy test must be confirmed within 7 days before the first dose, and they must agree to use effective contraception during the study drug administration period and for 120 days after the last dose. 12.Compliance with the trial schedule and follow-up procedures Exclusion Criteria: 1. Known squamous cell carcinoma, undifferentiated carcinoma, or other histological types of gastric cancer, or adenocarcinoma mixed with other histological types. 2. Patients with gastric cancer without HER2 expression. 3. Known active or untreated brain metastases, leptomeningeal metastases, spinal cord compression, or leptomeningeal disease. 4. History of gastrointestinal perforation or fistula within 6 months before the first dose. Eligible if the perforation or fistula has been surgically repaired and the investigator judges the condition to be resolved or stable. 5. Active diverticulitis, abdominal abscess, or gastrointestinal obstruction. 6. Inability to swallow, malabsorption syndrome, or uncontrolled nausea, vomiting, diarrhea, or other significant gastrointestinal conditions that affect drug intake and absorption. 7. Clinically significant bleeding events or clear predisposition to bleeding within 1 month before the first dose, such as gastrointestinal bleeding, bleeding gastric ulcers (with active bleeding signs on endoscopy), or vasculitis. 8. Symptomatic moderate to severe ascites requiring therapeutic paracentesis (exceptions include asymptomatic ascites detected only on imaging). Uncontrolled or moderate to large pleural effusions, pericardial effusions. 9. Signs or symptoms of unacceptable worsening of primary disease during screening, as judged by the investigator. Exclusion Criteria due to Concurrent Diseases or Comorbid Conditions: 10. Active or documented history of inflammatory bowel disease (such as Crohn's disease or ulcerative colitis). 11. Major surgery within 4 weeks before the start of study treatment that has not fully recovered, or anticipated need for major surgery during the study period. 12. Uncontrolled systemic diseases, including but not limited to diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, decompensated cirrhosis, nephrotic syndrome, angina pectoris, severe arrhythmias, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis. 13. Diagnosis of any malignancy other than gastric cancer within 5 years prior to entering the study. 14. Severe neurological or psychiatric disorders, including dementia, depression, and epilepsy. 15. Pregnant or breastfeeding women or individuals planning to conceive. 16. Presence of cardiovascular disease or cardiovascular risk factors. Drug Treatment-Related Exclusion Criteria: 17. Palliative radiotherapy for non-target lesions for symptom control is permitted, provided it was completed at least 2 weeks before the start of study treatment and any radiotherapy-induced adverse events have not resolved to ≤CTCAE Grade 1. 18. Prior treatment with immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapies, or any other antibody-drug conjugates targeting tumor immune mechanisms. 19. Palliative local treatment for non-target lesions or systemic nonspecific immunomodulatory treatments (e.g., interleukins, interferons, thymosin) or traditional Chinese medicine/herbal remedies with antitumor indications within 2 weeks before the first dose. 20. Toxicities from prior anticancer therapy have not resolved to ≤CTCAE Grade 1, except for: 1. Alopecia. 2. Pigmentation changes. 3. Peripheral neuropathy that has resolved to \<CTCAE Grade 2. 4. Late effects of radiothera