Combination treatment for advanced gastric cancer

Inclusion Criteria:

* Age: 18 years ≤ Age ≤ 75 years;
* Locally advanced or metastatic HER2 negative gastric or gastroesophageal junction adenocarcinoma confirmed by histopathology or cytology that cannot be resected;
* Has not received radiotherapy, chemotherapy, targeted therapy, or immunotherapy as the primary treatment option for advanced or metastatic diseases in the past; Participants with gastric or gastroesophageal junction adenocarcinoma who have previously received adjuvant or neoadjuvant chemotherapy, radiotherapy, and/or radiochemotherapy are eligible for enrollment as long as the last administration of the previous protocol occurred 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 Gault formula#
* Women of childbearing age must undergo a pregnancy test #serum# within 7 days before enrollment, and the result is negative. They are willing to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the trial drug; For males, surgical sterilization or agreement to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the trial drug should be considered; 9# Not participating in other clinical studies before and during treatment; 10# The subjects voluntarily joined this study, signed an informed 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 enter this study

  * Patients with allergies or suspected allergies to research drugs or similar drugs;
  * Suffering from other malignant tumors within the past 5 years, excluding skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
  * Received live vaccine within 4 weeks prior to enrollment or possibly during the study period;
  * Suffering from active autoimmune diseases or having a history of autoimmune diseases within 4 weeks prior to enrollment;
  * Previously received allogeneic bone marrow transplantation or organ transplantation;
  * 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 controlled with a single antihypertensive drug treatment #systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100mmHg#; Or use two or more antihypertensive drugs to control blood pressure in patients;
  * Urinary routine indicates that urine protein is ≥ 2+, and the 24-hour urine protein volume is\>1.0g;
  * The patient currently has digestive tract diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or other conditions determined by the researcher that may cause gastrointestinal bleeding or perforation;
  * Patients with significant evidence of bleeding tendency or medical history within the 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 ischemic attacks# within 12 months;
  * Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting surgery within 6 months prior to enrollment; Congestive heart 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 significant history of liver disease, including viral hepatitis \[known carriers of hepatitis B 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 RNA positivity #\>1 × 103 copies/mL, or other types of hepatitis or cirrhosis;
  * According to the judgment of the researchers, patients deemed unsuitable for inclusion in this study.