This study is a prospective, open-label, multicenter, randomized controlled clinical trial designed to enroll patients with previously untreated, resectable locally advanced adenocarcinoma of the upper stomach or gastroesophageal junction. After providing informed consent and meeting the eligibility criteria, enrolled patients will be randomized into two cohorts: Cohort 1 (experimental group) will receive sequential short-course radiotherapy (SCRT) followed by four cycles of SOX plus serplulimab as neoadjuvant therapy prior to surgery; Cohort 2 (control group) will receive four cycles of SOX plus serplulimab as neoadjuvant therapy before surgery. Postoperatively, all patients will continue with four cycles of SOX plus serplulimab as adjuvant therapy, with serplulimab maintained for one year. If patients do not meet the criteria for radical gastrectomy, alternative conservative treatments or surgical approaches will be considered following multidisciplinary team (MDT) discussion. The study aims to evaluate the efficacy and safety of SOX combined with serplulimab, and sequential SCRT followed by SOX plus serplulimab as neoadjuvant therapy leading to radical resection of gastric cancer. All enrolled patients will undergo PD-L1 expression analysis (CPS and TPS scores) and microsatellite instability status (MSI-H population). Where tissue availability and research center conditions permit, exploratory assessments will include minimal residual disease (MRD) measured at baseline, after neoadjuvant therapy, post-surgery, and after adjuvant therapy, tumor mutational burden (TMB), and whole-exome sequencing of tumor tissue. Radiological evaluations will be conducted every 3 months ± 1 week for the first 2 years post-surgery, then every 6 months ± 2 weeks up to 5 years, and annually thereafter until disease recurrence. Survival follow-up will occur every three months after recurrence. Safety visits will span from the first dose to 30 days after the last dose or initiation of new antitumor therapy.
The participant voluntarily joins this study, is able to complete the signing of the informed consent form, and demonstrates good compliance.
Age 18-75 years (at the time of signing the informed consent), regardless of gender.
Adenocarcinoma confirmed by histology and/or cytology, diagnosed as locally advanced according to the AJCC 8th edition criteria, with cTNM staged as cT3-4 or N+ M0 based on endoscopic ultrasound or contrast-enhanced CT/MRI, and the patient agrees to receive neoadjuvant therapy; the lesion is assessed by the investigator as resectable or potentially resectable; after MDT evaluation, radical resection is planned with standard D2 lymph node dissection.
Primary lesion site restrictions: (1) Adenocarcinoma of the gastroesophageal junction: Siewert type II-III; (2) Upper stomach cancer: the lower edge of the tumor is located within the upper third of the stomach, mainly involving the cardia, fundus, or upper part of the stomach body.
Undergo radiotherapy within 4 weeks before enrollment, or radionuclide therapy within 8 weeks.
Within 6 months before enrollment: esophageal or gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, fistulas, intestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding.
Diagnosis of malignancies other than gastric cancer within 5 years prior to first administration (excluding completely treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or completely resected carcinoma in situ).
Presence of distant metastasis (M1), including but not limited to: peritoneal metastasis (confirmed by imaging or laparoscopy), ascites or positive peritoneal lavage cytology, metastasis to organs such as liver, lung, or bone; cases where imaging suggests metastasis to para-aortic lymph nodes (No.16).