Neoadjuvant Apatinib Combined With Sintilimab and Perioperative SOX Versus Neoadjuvant Sintilimab Combined With Perioperative SOX for Intestinal Type of Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria:

1. Type of Participant and Disease Characteristics

2. Patients must have a pathologically confirmed diagnosis of HER-2 negative tumorand intestinal type gastric or gastroesophageal junction adenocarcinomaaccording to Lauren's histological subtypes.

3. Patients must have previously untreated locally advanced gastric orgastroesophageal junction adenocarcinoma (stage cT2 to cT4), with lymph nodesranging from N0 to N3 and no evidence of metastatic disease (M0).

4. Patients with Siewert type 2 or 3 tumors are eligible. Enrollment ofparticipants with Siewert type 1 tumors will be limited to those for whom theplanned treatment is perioperative chemotherapy and resection.

5. Demographics

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

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

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

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

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

• Females of childbearing potential are defined as those who are notsurgically sterile (e.g., bilateral tubal ligation, bilateraloophorectomy, or complete hysterectomy) or postmenopausal (defined as 12months 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, arerequired. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plusspermicide) to prevent pregnancy.

• Barrier methods include male condom plus spermicide, copper T intrauterinedevice, 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 herparticipation in the study or her partner's participation, she must promptlyinform her treating physician.

3. Organ Function

4. 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.

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

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

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

8. Cardiac Function: Cardiac function will be assessed using electrocardiogram andcolor Doppler ultrasound, and subjects must have had no myocardial infarctionwithin the last six months. Hypertension and other coronary heart diseases mustbe controllable.

• Females of childbearing potential are defined as those who are notsurgically sterile (e.g., bilateral tubal ligation, bilateraloophorectomy, or complete hysterectomy) or postmenopausal (defined as 12months 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, arerequired. Acceptable methods include a combination of a hormonal method (e.g., contraceptive pill) and a barrier method (e.g., male condom plusspermicide) to prevent pregnancy.

• Barrier methods include male condom plus spermicide, copper T intrauterinedevice, 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 herparticipation in the study or her partner's participation, she must promptlyinform her treating physician.

4. Informed Consent All subjects must provide written informed consent to participatein the study.

5. Other Inclusions

6. Prior Treatment: Patients must not have previously received any anti-tumortreatments, including radiotherapy, chemotherapy, targeted therapy, orimmunotherapy.

7. Plan to proceed to surgery following pre-operative chemotherapy based onstandard staging studies per local practice.

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

Exclusion Criteria:

1. Medical Conditions

2. Has a history of (non-infectious) pneumonitis that required steroids or hascurrent pneumonitis.

3. Has a known additional malignancy that is progressing or has required activetreatment within the past 5 years (except for cutaneous basal cell carcinoma,cutaneous squamous cell carcinoma, or carcinoma in situ that has undergonepotentially curative therapy).

4. Has an active infection requiring systemic therapy.

5. Has an active autoimmune disease that has required systemic treatment in thepast 2 years. (NOTE: Subjects with vitiligo, alopecia, Grave's disease, Type Idiabetes mellitus, hypothyroidism (e.g., following Hashimoto's syndrome) onlyrequiring hormone replacement on a stable dose (without adjustment in the first 4 weeks of study treatment), psoriasis or eczema not requiring systemictreatment (within the past 2 years), or conditions not expected to recur in theabsence of an external trigger are not excluded.)

6. Has any complications requiring systemic treatment with corticosteroids such asprednisone (> 10mg/day) or other immunosuppressive medications within 14 daysprior to the first administration. Replacement therapy (e.g., thyroxine,insulin, or physiologic corticosteroid replacement therapy for adrenal orpituitary insufficiency) is allowed.

7. History of primary immunodeficiency.

8. Has received a live vaccine or other immune-activating anti-tumor drugs (suchas interferon, interleukin, thymosin, or immunotherapy) within 30 days prior tothe first dose of study treatment.

9. Has a known history of active tuberculosis.

10. Known history of allogeneic organ transplantation and allogeneic hematopoieticstem cell transplantation.

11. Has a known severe allergy or hypersensitivity to sintilimab or apatinib or anyof the study chemotherapy agents and/or to any of their excipients.

12. Presence of any of the following cardiovascular and cerebrovascular diseases orcardiovascular and cerebrovascular risk factors:

• Grade II or higher myocardial ischemia or myocardial infarction, poorlycontrolled arrhythmia (including QTc interval ≥ 480 ms), grade III or IVcardiac insufficiency, or left ventricular ejection fraction (LVEF) < 50.0% as determined by ultrasonic cardiography.
• Cerebrovascular accident, transient ischemic attack, or otherarteriovenous thrombotic, embolic, or ischemic events.

2. Prior/Concomitant Therapy

3. Subjects who have already enrolled in another clinical study, unless it is anobservational, non-interventional clinical study, or they are in the follow-upperiod for an interventional study.

4. Subjects who have received any systemic or curative anti-tumor therapy,including radiotherapy, chemotherapy, targeted therapy.

5. Subjects who have previously received any anti-PD-1, anti-PD-L1 antibody, orany other antibody or drug therapy targeting T-cell co-stimulation orcheckpoint pathway, e.g. ICOS or agonists (e.g., CD40, CD137, GITR, and OX40,etc.).

6. Other exclusion criteria

7. Confirmed HER-2 positive tumor will be excluded.

8. Patients could not provide tumor samples and blood samples.

9. Pregnant or lactating patients, as well as patients with childbearing potentialwho plan to be pregnant within 5 months after the study; Women of childbearingshould receive a blood pregnancy test within 7 days before the study.