his study was a single-arm, open, single-center Phase ii clinical trial to observe and evaluate the efficacy and safety of CAPOX+ bevacizumab + tislelizumab in first-line treatment of ADVANCED gastroesophageal adenocarcinoma with CPS < 5.

This study targeted advanced gastric cancer patients who could not undergo radical treatment, who had not received systemic therapy before, or who had recurrence and metastasis more than 6 months after the end of adjuvant therapy.

The 6-month progression-free survival (PFS) rate will be used as the primary outcome indicator, and approximately 30 subjects will be enrolled.

Subject will receive CAPOX+ bevacizumab + tislelizumab continuously for a treatment cycle of 3 weeks after fully informed and signing informed consent, oxaliplatin will be stopped after 4-8 cycles, and other drugs will continue to be used until the treatment interruption event specified in the plan occurs. Post-treatment follow-up for safety and survival will continue after completion of treatment, and follow-up for tumor progression will also be conducted after completion of treatment for subjects who have not finished treatment for a cause of disease progression/death.

After the subjects were enrolled in the study, safety visits were conducted for each treatment cycle D1 before medication. Imaging will be performed every 2 cycles from the first year of treatment to assess efficacy, and every 3 cycles after 1 year until treatment ends, informed consent is withdrawn, or death.

Inclusion Criteria:

• At the same time, patients voluntarily participated in the study and signed informed consent.

• Either male or female, aged 18 or older.

• Patients diagnosed by pathological or cytological diagnosis of gastric cancer (GC), gastroesophageal junction carcinoma (GEJ) or esophageal adenocarcinoma had evidence of local advanced lesions or metastases that could not be surgically resected, and were mostly adenocarcinoma confirmed by histological examination.

• Anyway, she has no previous systemic therapy; Or had received neoadjuvant/adjuvant chemotherapy but experienced disease progression or recurrence 6 months after the end of treatment;

• PDL-1 CPS < 5, HER2 negative;

• Anyway, ECOG scores 0-1 on PS.Estimated survival ≥3 months;

• Anyway, their vital organs function according to the following rules:

  1. Hemoglobin (HGB) ≥90g/L;
  2. Neutrophil count (ANC) ≥1.5×109/L;
  3. Platelet count (PLT) ≥80×109/L;
  4. ALT and AST≤2.5×ULN;ALT and AST≤5×ULN for liver metastasis;
  5. Total bilirubin (TBIL) ≤1.5 times normal upper limit (ULN);
  6. Serum Cr≤1×ULN, endogenous creatinine clearance rate > 50ml/min (Cockcroft-Gault formula);
  7. Urinary protein < (++), or 24-hour urinary protein < 1.0g;

• Lent blood functions normally, without active bleeding or thrombotic disease:

  1. INR≤1.5×ULN;
  2. Partial thrombin time APTT≤1.5×ULN;
  3. Prothrombin time PT≤1.5×ULN;

• Women of reproductive age had to undergo a pregnancy test (serum or urine) which was negative within 7 days of enrollment, and volunteer to use an appropriate method of contraception during the observation period and for 12 weeks after the last study drug was given. For men, surgical sterilization or consent to use appropriate methods of contraception during the observation period and for 12 weeks after the last administration of the study drug;

• Anyway, people who comply are expected to be able to follow up on therapeutic outcomes and adverse reactions as required by the regimen.

Exclusion Criteria:

• Five years before first use of the study drug has been diagnosed as other malignant tumor, the effective treatment of basal cell carcinoma, squamous cell carcinoma of the skin and/or the effective removal of cervical cancer in situ and/or except breast cancer.
• Known allergy to oxaliplatin, PD-1 mab, bevacizumab or pharmaceutical excipients;Or severe allergic reactions to other monoclonal antibodies;
• Chauvinist has any active autoimmune disease or a history of autoimmune disease (e.g. interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis,vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (which can be included after hormone replacement therapy); Patients with complete remission of childhood asthma without intervention or vitiligo as adults may be included, but not those requiring medical intervention with bronchodilators;
• HBV DNA>500 IU/ mL (or 2000 copies /ml), HCV RNA>103 copies /ml, HBsAg+ and anti-HCV antibody positive;
• Lent has a history of HIV infection;
• Accuser spends 14 days prior to first using a study drug, regardless of nasal spray and inhaled corticosteroids or physiological doses of systemic steroids (i.e., no more than 10 mg/ day of prednisone or an equivalent pharmacophysiological dose of another corticosteroid);
• A live attenuated vaccine was administered either four weeks before the first dose or during the study period;
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation is known；
• Hypertension that cannot be controlled even with standard treatment (systolic blood pressure ≥160mmHg/ diastolic blood pressure ≥100mmHg);
• Either having poorly controlled cardiac clinical symptoms or disease, such as :(1) NYHA grade 2 or higher heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, or (4) clinically significant supracventricular or ventricular arrhythmias requiring treatment or intervention;
• Patients at risk of serious bleeding, including but not limited to severe bleeding (bleeding > 30 ml within 3 months), were evaluated by a physician who agreed to spend time on an endoscopic evaluation, which was subject to endoscopic evaluation.
• Either a thromboembolic event (including a stroke event and/or a transient ischemic attack) occurs within 6 months;
• Participates in another clinical trial, or participates in any other drug clinical study within four weeks, or at least five half-lives since the last study drug was taken;
• At the same time, participants in the Study underwent anti-tumor therapy including chemotherapy, radiotherapy and immunotherapy within 4 weeks prior to drug administration.
• At the same time, participants received palliative radiotherapy for bone metastasis within 2 weeks prior to the beginning of drug administration. Radiation therapy for other sites within the first 4 weeks;
• Regardless, toxicity from previous anti-tumor therapy does not return to CTCAE [version 5.0] level 0-1, as shown in the following.Except: a. hair loss;B. Pigmentation;C. Long-term toxicity caused by radiotherapy could not be recovered according to the judgment of researchers;
• Other conditions that the investigator deems inappropriate for inclusion;