First-line Treatment With RC48 Plus Sintilimab and S-1 in Advanced Gastric Cancer (RCTS2)

Inclusion Criteria: 1. Aged18-80 years, gender is not limited; 2. Pathologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma that is inoperable or has distant metastasis; 3. HER2-Positive (IHC3+or IHC2+/FISH+) ; 4. Has at least 1 measurable lesion as determined by RECIST 1.1; 5. There is no systematic treatment in the past, or the patient has received neoadjuvant/adjuvant chemotherapy, but the disease progresses or relapses more than 6 months after the end of treatment; 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 7. Adequate organ function; 8. The life expectancy is at least 3 months; Exclusion Criteria: 1. Allergy to any trial drug and its excipients, or serious allergy history, or contraindication of the trial drug; 2. Cardiovascular and cerebrovascular events that are not well controlled; 3. Has received systematic treatment with Chinese patent medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use for ascites control) before the first administration within 2 weeks. 4. Have a history of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute lung disease, or systemic disease with poor control (including but not limited to diabetes, hypertension, etc.); 5. Have a history of active immune deficiency or autoimmune diseases, including HIV positive test, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or autoimmune diseases; 6. Severe chronic or active infection requires systemic antibacterial, antifungal or antiviral treatment, including tuberculosis infection.Have a history of active tuberculosis infection ≥ 1 year before recruitment should also be excluded, unless proved has been completed appropriate treatment; 7. Brain metastasis or leptomeningeal metastasis; 8. Clinically significant pleural effusion, pericardial effusion or ascites should be drained for many times within 2 weeks before the first administration of the trial drug; 9. Has a second clinically detectable primary malignant tumor at the time of recruitment, or there were other malignant tumors in the past 5 years (except for fully treated skin basal cell carcinoma or cervical carcinoma in situ); 10. Any major surgery was performed ≤ 28 days before the first trial drug administration; 11. History of allogeneic stem cell transplantation or organ transplantation;