Neoadjuvant Nab-Paclitaxel Plus Oxaliplatin, S-1, and Sintilimab in Early-Onset Resectable Gastric Cancer

Inclusion Criteria:

* Participants must meet all of the following inclusion criteria:
* Male or female, aged ≥16 and ≤45 years;
* Karnofsky performance score ≥70% or ECOG performance status 0-1;
* Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
* For gastric body cancer: clinical stage cT3-T4a N+ M0;
* For GEJ cancer: clinical stage cT2-T4a N+ M0;
* For cT4b Nany M0 cases: location may be gastric body or GEJ.
* Staging is based on contrast-enhanced CT, MRI (if needed), and endoscopic ultrasonography (EUS) (if needed);
* Assessed as resectable after multidisciplinary team (MDT) discussion;
* Surgical evaluation confirms that D2 radical gastrectomy is feasible;
* Sufficient physical condition and organ function to tolerate major abdominal surgery;
* Baseline laboratory tests meet the following criteria:
* Hemoglobin ≥90 g/L
* Absolute neutrophil count (ANC) ≥1.5×10⁹/L
* Platelets ≥100×10⁹/L
* ALT and AST ≤2.5× upper limit of normal (ULN)
* Alkaline phosphatase (ALP) ≤2.5× ULN
* Total bilirubin \<1.5× ULN
* Serum creatinine \<1× ULN
* Serum albumin ≥30 g/L
* No severe comorbidities that may limit life expectancy to \<3 years;
* Participant is willing and able to comply with the study protocol during the study period;
* Written informed consent must be signed before screening. Participants must understand their right to withdraw at any time without any loss of benefits;
* Willing to provide blood and tissue samples.

Exclusion Criteria:

* Participants meeting any of the following criteria will be excluded:
* Patients with HER-2 positive gastric cancer, as determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH);
* Patients with dMMR (deficient mismatch repair) or MSI-H (microsatellite instability-high) tumors, as determined by IHC;
* Pregnant or breastfeeding women;
* Prior treatment for gastric cancer with cytotoxic chemotherapy, radiotherapy, or immunotherapy;
* History of other malignancies within the past 5 years;
* Active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis;
* Active inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis;
* Currently receiving systemic corticosteroids or other immunosuppressive therapy;
* Prior organ transplantation or use of anti-rejection medications;
* Active tuberculosis, HIV infection, or severe active hepatitis B or C;
* History of uncontrolled epilepsy, central nervous system disorders, or psychiatric illnesses that, in the investigator's judgment, may interfere with informed consent or compliance with oral medication;
* Clinically significant (active) cardiac diseases, including symptomatic coronary artery disease, NYHA class II or above congestive heart failure , severe arrhythmias requiring medical intervention, or myocardial infarction within the past 12 months;
* Presence of upper gastrointestinal obstruction that may impair the oral intake or absorption of S-1;
* Severe uncontrolled recurrent infections or other uncontrolled serious comorbidities;
* Use of any investigational drugs within 4 weeks prior to study enrollment.