A Study on the Safety and Efficacy of the Combination of Candenizumab, Lenvatinib, and SOX Regimen in the Treatment of HER2 Negative Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Patients

Inclusion Criteria:

• Age: 18 years ≤ Age ≤ 75 years;
• Locally advanced or metastatic HER2 negative gastric or gastroesophageal junctionadenocarcinoma confirmed by histopathology or cytology that cannot be resected;
• Has not received radiotherapy, chemotherapy, targeted therapy, or immunotherapy as theprimary treatment option for advanced or metastatic diseases in the past; Participantswith gastric or gastroesophageal junction adenocarcinoma who have previously receivedadjuvant or neoadjuvant chemotherapy, radiotherapy, and/or radiochemotherapy areeligible for enrollment as long as the last administration of the previous protocoloccurred at least 6 months prior to randomization.
• At least one measurable lesion #see Appendix 2#;
• ECOG PS: 0-1 points #see Appendix 4#;
• Estimated survival time>3 months;
• The main organ function is normal and meets the following criteria:
• Blood routine examination must meet the following criteria#no blood transfusion within 14 days#

1. HB ≥ 100g/L,
2. WBC ≥ 3 × 109/L
3. ANC ≥ 1.5 × 109/L,
4. PLT ≥ 100 × 109/L;

• Biochemical examination must meet the following standards:

1. BIL<1.5 times the upper limit of normal value #ULN#,
2. ALT and AST<2.5ULN, GPT ≤ 1.5 × ULN;
3. Serum Cr ≤ 1ULN, endogenous creatinine clearance rate>60ml/min #Cockcroft Gaultformula#

• Women of childbearing age must undergo a pregnancy test #serum# within 7 days beforeenrollment, and the result is negative. They are willing to use appropriate methods ofcontraception during the trial period and 8 weeks after the last administration of thetrial drug; For males, surgical sterilization or agreement to use appropriate methodsof contraception during the trial period and 8 weeks after the last administration ofthe trial drug should be considered; 9# Not participating in other clinical studiesbefore and during treatment; 10# The subjects voluntarily joined this study, signed aninformed consent form, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

• If a subject meets any of the following conditions, they will not be allowed to enterthis study
• Patients with allergies or suspected allergies to research drugs or similardrugs;
• Suffering from other malignant tumors within the past 5 years, excluding skinbasal cell or squamous cell carcinoma after radical surgery, or cervicalcarcinoma in situ;
• Received live vaccine within 4 weeks prior to enrollment or possibly during thestudy period;
• Suffering from active autoimmune diseases or having a history of autoimmunediseases within 4 weeks prior to enrollment;
• Previously received allogeneic bone marrow transplantation or organtransplantation;
• The patient currently has any disease or condition that affects drug absorption,or the patient is unable to take medication orally;
• The patient currently has hypertension that cannot be controlled by medication,which is defined as: patients with hypertension who cannot be well controlledwith a single antihypertensive drug treatment #systolic blood pressure ≥ 150mmHg, diastolic blood pressure ≥ 100mmHg#; Or use two or more antihypertensivedrugs to control blood pressure in patients;
• Urinary routine indicates that urine protein is ≥ 2+, and the 24-hour urineprotein volume is>1.0g;
• The patient currently has digestive tract diseases such as active gastric andduodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors,or other conditions determined by the researcher that may cause gastrointestinalbleeding or perforation;
• Patients with significant evidence of bleeding tendency or medical history withinthe 3 months prior to enrollment #bleeding>30 mL within 3 months, vomiting blood,black stool, and rectal bleeding#, hemoptysis #fresh blood>5 mL within 4 weeks#,or thromboembolic events #including stroke events and/or transient ischemicattacks# within 12 months;
• Cardiovascular diseases with significant clinical significance, including but notlimited to acute myocardial infarction, severe/unstable angina, or coronaryartery bypass grafting surgery within 6 months prior to enrollment; Congestiveheart failure is classified by the New York Heart Association #NYHA# as>level 2;Ventricular arrhythmia requiring medication treatment; Electrocardiogram #ECG#shows a QT interval of ≥ 480 milliseconds;
• Active or uncontrolled severe infection #≥ CTCAE level 2 infection#;
• Known human immunodeficiency virus #HIV# infection; Known clinically significanthistory of liver disease, including viral hepatitis [known carriers of hepatitisB virus #HBV# must exclude active HBV infection, i.e. HBV DNA positivity #>1 × 104 copies/mL or>2000 IU/ml#; Known hepatitis C virus infection #HCV# and HCV RNApositivity #>1 × 103 copies/mL, or other types of hepatitis or cirrhosis;
• According to the judgment of the researchers, patients deemed unsuitable forinclusion in this study.