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

Inclusion Criteria:

1. Aged18-75 years, gender is not limited;

2. Pathologically confirmed locally advanced gastric or gastroesophageal junctionadenocarcinoma 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 receivedneoadjuvant/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, orcontraindication of the trial drug;

2. Cardiovascular and cerebrovascular events that are not well controlled;

3. Has received systematic treatment with Chinese patent medicine or immunomodulatorydrugs (including thymosin, interferon, interleukin, except for local use for ascitescontrol) before the first administration within 2 weeks.

4. Have a history of interstitial lung disease, non-infectious pneumonia, pulmonaryfibrosis, acute lung disease, or systemic disease with poor control (including butnot limited to diabetes, hypertension, etc.);

5. Have a history of active immune deficiency or autoimmune diseases, including HIVpositive test, or have other acquired or congenital immune deficiency diseases, orhave a history of organ transplantation or autoimmune diseases;

6. Severe chronic or active infection requires systemic antibacterial, antifungal orantiviral treatment, including tuberculosis infection.Have a history of activetuberculosis infection ≥ 1 year before recruitment should also be excluded, unlessproved has been completed appropriate treatment;

7. Brain metastasis or leptomeningeal metastasis;

8. Clinically significant pleural effusion, pericardial effusion or ascites should bedrained for many times within 2 weeks before the first administration of the trialdrug;

9. Has a second clinically detectable primary malignant tumor at the time ofrecruitment, or there were other malignant tumors in the past 5 years (except forfully treated skin basal cell carcinoma or cervical carcinoma in situ);

10. Any major surgery was performed ≤ 28 days before the first trial drugadministration;

11. History of allogeneic stem cell transplantation or organ transplantation;