This is a prospective, single-arm, open-label，single-center, phase II study, aiming to to evaluate the surgical conversion feasibility of AK104 combined with apatinib, paclitaxel and S-1 in unresectable stage IV G/GEJ cancer.

Eligible patients receive AK104 (10mg/kg, iv, Q3W) combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis :90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycles. Patients assessed by Multi-Disciplinary Treatment (MDT) to meet the criteria for surgical resection undergo gastrectomy.

Inclusion Criteria:

1. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
2. Clinically diagnosed unresectable stage IV gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma by CT/MRI/Positron Emission Tomography (PET) -CT.
3. Not received prior systemic therapy for stage IV G/GEJ adenocarcinoma
4. At least one measurable tumor lesion per RECIST v1.1;
5. Major organ functions are adequate;
6. Expected survival is ≥ 3 months;
7. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1;

Exclusion Criteria:

1. Human Epidermal GrowthFactor Receptor 2 (HER2)-positive G/GEJ adenocarcinoma;
2. Previously received immune checkpoint inhibitors, including but not limited to programmed death 1 (PD-1) inhibitors and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors;
3. Central nervous system, lung, or bone metastases;
4. Known history of active or autoimmune disease;
5. Known history of other malignancies;
6. Known history of severe cardiovascular and cerebrovascular diseases;
7. Known history of gastrointestinal bleeding within the past 3 months or significant tendency to gastrointestinal bleeding;
8. Active infection or fever of unknown origin;
9. Known history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function;
10. Known history of immunodeficiency, positive HIV antibody (HIVAb) test, or other acquired or congenital immunodeficiency disorder, or active hepatitis;
11. Known history of mental disorder or psychoactive substance abuse;
12. Hypersensitivity to the drugs of this regimen;