Inclusion Criteria:
1. Patients with histopathological confirmed gastric/GEJ adenocarcinoma.
2. The clinical stage was IV, according to AJCC 8th edition.
3. Patients had received at least two systematic therapies.
4. Patients had received or not received immunotherapy.
5. The patients received or did not receive anti-VEFGR targeted therapy in the last treatment (e.g., Bevacizumab, Ramucirumab, anti-VEGFR TKIs, etc.).
6. Age ≥18.
7. ECOG physical status score is 0-2 without deterioration within 2 weeks before the first administration of the investigational drug.
8. Adequate organ function according to the following laboratory test values:
1. Hemoglobin value ≥90g/L.
2. White blood cell count ≥3.5\*109/L.
3. Absolute neutrophil count ≥1.5\*109/L.
4. Platelet count ≥100\*109/L.
5. Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥60ml/min.
6. Total serum bilirubin ≤1.5 upper normal limit (ULN).
7. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5 upper limit of normal value (ULN).
9. With a full understanding of the study, each participant volunteered to participate in this study and signed the informed consent (ICF) with good compliance and follow-up.
Exclusion Criteria:
1. Histopathological types other than adenocarcinoma include squamous cell carcinoma, adenosquamous carcinoma, neuroendocrine carcinoma, etc.
2. Known hypersensitivity or previous treatment with trifluridine/tipiracil or any of its components or excipients.
3. Known hypersensitivity to any component or excipients of bevacizumab.
4. Requirement for systemic corticosteroids (\>10mg/day of prednisone or equivalent other corticosteroids, for a continuous treatment of ≥7 days) or immunosuppressive therapy within 14 days before enrollment; excluding inhaled or topical steroid use, or hormone therapy for adrenal insufficiency at physiological replacement doses; short-term (≤7 days) corticosteroids are allowed for prevention (e.g., contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity caused by contact allergens).
5. Receipt of a live vaccine (including attenuated live vaccines) or systemic immunostimulants (including but not limited to interferon or interleukin-2) within 28 days before enrollment.
6. Past or current interstitial pneumonia disease, except for those non-active and not requiring hormone therapy determined by the investigator.
7. Past or current autoimmune disease, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophyseal inflammation, uveitis, autoimmune hepatitis, systemic sclerosis (scleroderma, etc.), Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. except for type I diabetes, hormonally replaced euthyroidism (including autoimmune thyroid disease causing hypothyroidism), psoriasis or vitiligo not requiring systemic treatment.
8. History of hypersensitivity, severe allergic reactions, or intolerance to antibody medications; history of significant allergies to drugs, foods, or other substances (e.g., severe allergic reactions, immunologically mediated hepatotoxicity, immunologically mediated thrombocytopenia, or anemia).
9. History of allogeneic bone marrow or organ transplantation.
10. Inability to swallow, intestinal obstruction, or other factors affecting drug intake and absorption.
11. Recurrent bleeding that cannot be controlled (as judged by the investigator to be at risk for major gastrointestinal bleeding, etc.).
12. Major surgery was performed within 4 weeks before the first study drug treatment (biopsy procedures excepted).
13. Concurrent malignancy within the past 5 years, except for those adequately treated cervical carcinoma in situ, localized squamous cell carcinoma of the skin, basal cell carcinoma, asymptomatic prostate cancer, ductal carcinoma in situ of the breast, well-differentiated thyroid cancer, or urinary tract epithelial cancer \< T1, adequately treated lung carcinoma in situ, or other malignancies considered cured.
14. History of gastrointestinal perforation and/or fistula within the past 6 months, history of intestinal obstruction (including incomplete obstruction requiring parenteral nutrition), inflammatory bowel disease, or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
15. Any severe cardiac insufficiency, including left ventricular ejection fraction (LVEF) \< 50%, congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0 or New York Heart Association grade ≥ 2), myocardial infarction, severe/unstable angina, stroke, or transient ischemic attack (TIA) within 6 months before enrollment.
16. Uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg) and diabetes (fasting blood glucose \> 8.9 mmol/l).
17. History of ventricular tachycardia or torsades de pointes. Any resting ECG with significant clinical abnormalities in rhythm, conduction, or morphology, such as QTc \> 450 msec for males, QTc \> 470 msec for females, complete left bundle branch block, or third-degree atrioventricular block.
18. Active hepatitis B (must meet both HBsAg positive and HBV DNA ≥ 2000 IU/ml, or ≥ 104 copies, excluding hepatitis due to drugs or other causes), active hepatitis C (must meet both anti-HCV antibody positive and HCV RNA positive), syphilis (further testing for syphilis titer is required for those with positive syphilis antibodies), or human immunodeficiency virus (HIV) infection.
19. Pulmonary embolism or deep vein thrombosis occurring within 3 months before the first administration of the study drug (excluding thrombosis caused by catheters such as port, PICC, etc.).
20. Active pulmonary tuberculosis (TB), currently receiving anti-tuberculosis treatment, or those who have received anti-tuberculosis treatment within 1 year before the first dose.
21. Severe primary pulmonary disease, currently requiring continuous oxygen therapy for clinical active interstitial lung disease (ILD) or a history of pneumonia.
22. Uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infection requiring intravenous anti-infective treatment within 2 weeks before the first administration of the study drug.
23. Known history of substance abuse or drug addiction.
24. Pregnant or lactating women.
25. Fertile but unwilling to use effective contraceptive measures.
26. Any other diseases, metabolic disorders, or laboratory test abnormalities that the investigator has reason to suspect would make the patient unsuitable for treatment with the study drug, would affect the interpretation of the study results, or would place the patient at high risk.
