The goal of this clinical trial is to evaluate postoperative adaptive adjuvant therapy in patients with gastric or gastroesophageal junction adenocarcinoma after neoadjuvant chemotherapy plus immunotherapy and radical gastrectomy.The main questions it aims to answer are:

1. In patients with poor pathological response, does switching to a alternative postoperative treatment regimen improve survival?
2. In patients with complete pathological response, can observation without routine postoperative treatment maintain favorable survival outcomes? Participants will be assigned to different cohorts according to their pathological response after surgery and will be followed regularly for recurrence, survival, and treatment-related side effects.

This prospective clinical trial will enroll patients with gastric or gastroesophageal junction adenocarcinoma who have received neoadjuvant chemotherapy plus immunotherapy followed by radical gastrectomy. Participants will be assigned to predefined cohorts according to postoperative pathological response and pathological stage.

Patients with poor pathological response, defined as TRG 3 and ypT3-4N2-3M0 disease, will be evaluated to determine whether switching to a alternative postoperative treatment regimen improves survival and remains safe compared with continuing the original treatment regimen. For patients with complete pathological response, defined as TRG 0 and ypT0N0M0 disease, will be evaluated to determine whether observation without routine postoperative treatment maintain favorable survival outcomes.

The study aims to assess whether postoperative treatment can be adapted according to pathological response after neoadjuvant therapy, rather than applying the same postoperative treatment strategy to all patients. The results may help develop more individualized postoperative management strategies for patients at very high or very low risk of recurrence after neoadjuvant therapy and radical surgery.

Key Inclusion Criteria:

1. Voluntarily signed written informed consent.

2. Aged 18 to 75 years, inclusive, regardless of sex.

3. Underwent radical gastrectomy with D2 or more extended lymphadenectomy and achieved R0 resection. Surgical approaches may include open or laparoscopic surgery.

4. Histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma.

5. Received preoperative neoadjuvant immunotherapy combined with chemotherapy, including oxaliplatin plus fluoropyrimidine-based chemotherapy. Immunotherapy may include anti-PD-1 monoclonal antibodies, anti-PD-L1 monoclonal antibodies, PD-1/CTLA-4 bispecific antibodies, and other immune checkpoint inhibitors.

6. Eligible for one of the following predefined cohorts:

   • Cohort 1: TRG grade 3 and postoperative pathological stage ypT3-4N2-3M0.
   • Cohort 2: TRG grade 0 and postoperative pathological stage ypT0N0M0.

7. ECOG performance status of 0 or 1.

8. No evidence of metastasis or recurrence on postoperative imaging before enrollment.

9. Adequate organ function, defined as hematologic, hepatic, renal, and thyroid function meeting the protocol-specified criteria based on laboratory tests performed within 14 days before randomization.

10. Willing and able to comply with the study treatment, scheduled visits, laboratory tests, and other study procedures.

11. Female participants of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during the study and for 6 months after the last dose of study treatment. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose of study treatment.

Key Exclusion Criteria:

1. Presence of liver, peritoneal, or other distant metastases.
2. Inability to take oral medications.
3. Unresolved postoperative complications at the time of randomization, such as postoperative infection, anastomotic leakage or wound dehiscence, gastrointestinal bleeding, pancreatic fistula, or intestinal obstruction.
4. Uncontrolled pericardial effusion, uncontrolled pleural effusion, or clinically significant moderate or greater ascites at screening, defined as any of the following: pleural effusion or ascites with clinical symptoms and detectable by physical examination; or pleural effusion or ascites requiring drainage and/or intracavitary treatment during screening.
5. Underwent any surgery requiring general anesthesia that was not related to gastric cancer within 28 days before randomization.
6. History of or current diagnosis of another malignancy within 5 years.
7. Active or prior autoimmune disease that may relapse or require immunosuppressive treatment within 2 weeks or during the study period; or a history of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency disease; or a history of organ transplantation.
8. Participation in another clinical study, or any condition that may interfere with the interpretation of the study results.
9. Any other severe acute or chronic disease that, in the investigator's judgment, may increase the risk associated with study participation or study treatment.
10. Active or uncontrolled infection requiring systemic antibiotic therapy within 2 weeks before randomization or at the time of randomization.
11. Diagnosis of interstitial pneumonia, noninfectious pneumonitis, pulmonary fibrosis, or acute lung disease.
12. Active tuberculosis within 1 year or previous anti-tuberculosis treatment.
13. Female participants who are pregnant, breastfeeding, or planning to become pregnant during treatment or within 6 months after the end of treatment.
14. History of psychotropic drug abuse with inability to discontinue, or presence of a psychiatric disorder.
15. Patients considered unsuitable for participation in this study by the investigator.