SHR-1701 With or Without Apatinib in Combination With Chemotherapy as Neoadjuvant Therapy for Gastric Cancer

This study enroll patients with resectable, locally advanced (cT3-4aN+M0) gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who have not received anticancer therapy. Eligible subjects will be randomized in a 1:1 ratio to one of the two intervention arms. Arm 1：SHR-1701, apatinib, and SOX. Arm2: SHR-1701 and SOX. Arm 1 incorporates a safety run-in phase, during which the first 6 subjects enrolled in this cohort will undergo safety observation.

Inclusion criteria

• Patients voluntarily participate in this study and provide signed informed consent;
• Age ≥18 years old;
• Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (Siewert Type II and Type III adenocarcinoma are permitted);
• Clinically staged as T3-4aN+M0 by CT or MRI (per AJCC 8th edition), deemed resectable
• No prior antitumor therapy (e.g., surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.);
• Plan to proceed to surgery after completion of neoadjuvant therapy;
• Able to swallow tablets normally;
• Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Estimated life expectancy ≥12 months;
• Has adequate organ function.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose and must agree to use a highly effective method of contraception during the study and for 3 months after the last dose of SHR-1701, or 8 weeks after apatinib, or 6 months after chemotherapy (whichever is longer). Male subjects with partners of childbearing potential must be surgically sterile or agree to use a highly effective method of contraception during the study and for 3 months after the last dose of SHR-1701, or 8 weeks after apatinib, or 3 months after chemotherapy (whichever is longer), and must not donate sperm during the study.

Exclusion criteria

• Known HER2 positive
• Need transthoracic surgical approach Based on the investigator's judgment
• Known peritoneal metastasis or positive peritoneal cytology (CY1P0) or T4b (according to AJCC 8th edition); 4 Presence of unresectable factors, including unresectability due to tumor-related reasons, contraindications to surgery, or refusal of surgery;

• Previous or concurrent malignancies, except for cured basal cell carcinoma of skin, carcinoma in situ of cervix, and carcinoma in situ of breast; 6. Uncontrolled hypertension ( systolic ≥140 mmHg or diastolic ≥90 mmHg despite antihypertensive therapy)； 7. Known hypersensitivity to any of the study drugs or excipients; 8. Known hereditary or acquired bleeding and thrombotic tendencies (e.g. hemophiliacs, coagulation disorders, thrombocytopenia, etc.); 9. Congenital or acquired immune deficiency (e.g. HIV infected)