This study is a prospective, umbrella-design, Phase II clinical trial. Eligible participants with advanced or metastatic gastric cancer who are treatment-naïve for advanced-stage systemic therapy will undergo biomarker profiling (HER2, CLDN18.2, and PD-L1) via next-generation sequencing (NGS) or immunohistochemistry (IHC). Participants will be stratified into distinct molecular subtypes and assigned subtype-specific therapeutic regimens. The primary objectives are to assess treatment efficacy (e.g., objective response rate) and safety profiles across molecularly defined cohorts.
Age ≥18 years, regardless of gender;
Histologically or pathologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction;
Advanced or metastatic disease with no prior systemic therapy for advanced-stage disease (Patients who relapsed >6 months after completing neoadjuvant/adjuvant therapy are eligible, with prior neoadjuvant/adjuvant regimens not counted as prior lines of therapy);
At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1);
History of gastrointestinal perforation and/or fistula within 6 months prior to treatment, or active gastrointestinal bleeding within 3 months;
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage;
Known history of hypersensitivity to any component of the investigational drug(s) or excipients;
Received any investigational drug within 4 weeks prior to the first dose of the study drug or within 5 half-lives of the last investigational agent (whichever is shorter);
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Treatment groupsSee each treatment group below.