A Phase II, Multicenter, Randomized, Controlled Clinical Study Comparing the Efficacy and Safety of Sintilimab Plus SOX Versus SOX Alone as Adjuvant Therapy for PD-L1-Positive, Stage pN3 Gastric Cancer
This study intends to enroll gastric cancer patients who are PD-L1 positive and pathologically confirmed as Stage N3. Enrolled patients will be randomly assigned to receive either standard adjuvant SOX regimen or SOX regimen combined with sintilimab. The objective of the study is to determine whether adding a PD-1 inhibitor to postoperative chemotherapy can improve the Disease-Free Survival (DFS) rate in patients with Stage N3 gastric cancer.
• Sign a written informed consent form prior to the initiation of any study-related procedures.
• Aged between 18 and 75 years.
• Have undergone radical resection with D2 or wider lymph node dissection and achieved R0 resection status.
• No prior systemic anti-tumor treatment (i.e., neoadjuvant therapy) before surgery.
• Histopathologically confirmed gastric adenocarcinoma.
• Pathological stage classified as TxN3M0 according to the 8th edition of the AJCC Cancer Staging Manual.
• PD-L1 Combined Positive Score (CPS) ≥ 1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Expected survival time ≥ 6 months.
• Adequate organ function, with subjects meeting the following laboratory criteria before enrollment:
⁃ Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L without the use of granulocyte colony-stimulating factor (G-CSF) within the past 14 days.
⁃ Platelet count ≥ 100×10⁹/L without blood transfusion within the past 14 days. Hemoglobin \> 9 g/dL without blood transfusion or use of erythropoietin within the past 14 days.
⁃ Total bilirubin ≤ 1.5×Upper Limit of Normal (ULN); subjects with total bilirubin \> 1.5×ULN but direct bilirubin ≤ ULN are also eligible.
⁃ Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5×ULN. Serum creatinine ≤ 1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min.
⁃ Adequate coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5×ULN.
⁃ Normal thyroid function, defined as Thyroid-Stimulating Hormone (TSH) within the normal range. Subjects with baseline TSH outside the normal range are eligible if total T3 (or free T3, FT3) and free T4 (FT4) are within the normal range.
⁃ Myocardial enzyme profile within the normal range (subjects with isolated laboratory abnormalities deemed clinically insignificant by the investigator are also eligible).
• For female subjects of childbearing potential, a negative urine or serum pregnancy test must be obtained within 3 days before the first administration of the study drug (Cycle 1, Day 1). A blood pregnancy test is required if the urine pregnancy test result is inconclusive. Non-childbearing potential is defined as postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy.
• All subjects (male and female) at risk of conception must use contraceptive methods with a yearly failure rate of less than 1% throughout the treatment period and until 120 days after the last administration of the study drug (or 180 days after the last administration of chemotherapy drugs).