• Type of Participant and Disease Characteristics

∙ Patients must have a pathologically confirmed diagnosis of HER-2 negative tumor and intestinal type gastric or gastroesophageal junction adenocarcinoma according to Lauren's histological subtypes.

‣ Patients must have previously untreated locally advanced gastric or gastroesophageal junction adenocarcinoma (stage cT2 to cT4), with lymph nodes ranging from N0 to N3 and no evidence of metastatic disease (M0).

‣ Patients with Siewert type 2 or 3 tumors are eligible. Enrollment of participants with Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection.

• Demographics

∙ Male or female subjects must be between the ages of ≥ 18 and ≤ 75 years at the time of signing the informed consent.

‣ Expected Survival: The expected survival time must be ≥ 12 weeks.

‣ Performance Status: Subjects must have an ECOG performance status of 0 or 1.

‣ Male Contraception: Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use an effective method of contraception from Day 1 through 120 days after receipt of the final dose of the investigational product. It is strongly recommended for the female partner of a male subject to also use an effective method of contraception throughout this period.

‣ Female subjects of childbearing potential must be willing to use adequate contraception methods throughout the study and for 120 days after the last dose of the study drug. The decision to discontinue contraception after this time point should be discussed with the attending physician. Periodic abstinence, contraceptive rhythm methods, and withdrawal are not acceptable forms of contraception.

⁃ Females of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).

• Highly effective contraception methods, resulting in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, are required. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plus spermicide) to prevent pregnancy.

• Barrier methods include male condom plus spermicide, copper T intrauterine device, and levonorgestrel-releasing intrauterine system.

• ii.Hormonal methods include implants, hormone injection, combined pill, minipill, and patch.

⁃ If a female subject becomes pregnant or suspects pregnancy during her participation in the study or her partner's participation, she must promptly inform her treating physician.

• Organ Function

∙ Blood Routine (no blood transfusion within 14 days): WBC ≥ 3.0 × 10\^9/L; ANC ≥ 1.5 × 10\^9/L; PLT ≥ 100 × 10\^9/L; HGB ≥ 80 g/L.

‣ Hepatic Function: Total bilirubin (TBIL) ≤ 1.5 × ULN, or direct bilirubin ≤ ULN for those with total bilirubin levels 1.5 × ULN and ALT/AST levels ≤ 2.5 × ULN.

‣ Renal Function: Creatinine (Cr) ≤ 1.5 × ULN or Creatinine Clearance (CrCl) ≥ 60 mL/min for those with Cr \> 1.5 × ULN.

‣ Coagulation Function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.

‣ Cardiac Function: Cardiac function will be assessed using electrocardiogram and color Doppler ultrasound, and subjects must have had no myocardial infarction within the last six months. Hypertension and other coronary heart diseases must be controllable.

⁃ Females of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).

• Highly effective contraception methods, resulting in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, are required. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plus spermicide) to prevent pregnancy.

• Barrier methods include male condom plus spermicide, copper T intrauterine device, and levonorgestrel-releasing intrauterine system.

• iv.Hormonal methods include implants, hormone injection, combined pill, minipill, and patch.

⁃ If a female subject becomes pregnant or suspects pregnancy during her participation in the study or her partner's participation, she must promptly inform her treating physician.

• Informed Consent All subjects must provide written informed consent to participate in the study.

• Other Inclusions

∙ Prior Treatment: Patients must not have previously received any anti-tumor treatments, including radiotherapy, chemotherapy, targeted therapy, or immunotherapy.

‣ Plan to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.

‣ Be willing to provide tissue and blood sample from a tumor lesion at baseline and at time of surgery