This is a prospective, single-center, open, single-arm clinical study to observe and evaluate the efficacy and safety of Fruquintinib and Adebrelimab combined with paclitaxel/albumin paclitaxel for second-line treatment of advanced gastric cancer.

Since the first-line ICIs application of gastric cancer is mainly PD-1 antibody, this study intends to screen first-line patients exposed to PD-1 antibody and with long survival (PFS longer than 9 months) to receive second-line PD-L1 antibody for re-challenge and combine with Fruquintinib and paclitaxel to explore whether it can further increase the effect of second-line treatment.

Inclusion Criteria:

1. Age ≥18 years old.

2. The ECOG score is 0-1 and does not deteriorate within 7 days.

3. Patients with histologically confirmed, metastatic, or unresectable locally advanced gastric cancer or GEJ adenocarcinoma.

4. Previously received one systemic chemotherapy regimen for this cancer and progressed; Or have received adjuvant chemotherapy, but have disease progression or recurrence within 6 months after the end of treatment.

5. First-line exposure to PD-1 antibodies and first-line treatment of PFS greater than 9 months.

6. Measurable lesions that meet RECIST 1.1 criteria.

7. Have adequate organ and bone marrow function, laboratory tests meet the following requirements:

   1. HGB≥90g/L;
   2. NEUT≥1.5×10^9/L;
   3. PLT ≥80×10^9/L;
   4. TBIL≤1.5 times upper limit of normal value (ULN);
   5. ALT and AST≤2.5 x ULN; In liver metastasis, ALT and AST≤5×ULN;
   6. Endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula);
   7. Urinary protein < (++), or 24-hour urinary protein volume < 1.0 g.

8. Normal coagulation function, no active bleeding

   1. International standardized ratio INR≤1.5;
   2. Partial thromboplastin time APTT≤1.5 ULN.

9. Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and within 8 weeks after the last dose of the study drug; For men, they should be surgically sterilized or consent to an appropriate method of contraception during the observation period and for 8 weeks after the last administration of the study drug.

10. Expected survival ≥3 months.

11. Patients voluntarily joined the study and signed an informed consent form (ICF).

12. It is expected that the compliance is good, and the efficacy and adverse reactions can be followed up according to the protocol requirements.

Exclusion Criteria:

1. Previous treatment with VEGFR inhibitors;
2. Previously received paclitaxel therapy (except for those who received paclitaxel therapy in neoadjuvant or adjuvant therapy, and the treatment ended more than 6 months after the disease progression);
3. Receive live vaccine within 4 weeks prior to enrollment or possibly during the study period;
4. Had active autoimmune disease or history of autoimmune disease within 4 weeks prior to enrollment;
5. Previously received allogeneic bone marrow transplantation or organ transplantation;
6. Hypertension that could not be controlled by drugs before enrollment was defined as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg;
7. Had any disease or condition affecting drug absorption before enrollment, or the patient could not take drugs orally;
8. Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerative colitis, or active bleeding of unexcised tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers before enrollment;
9. Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding within 3 months > 30 mL, hematemesis, stool, stool blood), hemoptysis, or thromboembolic events (including stroke events and/or transient ischemic attacks) within 12 months;
10. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure > Level 2; Ventricular arrhythmias requiring medical treatment; LVEF (Left ventricular Ejection Fraction) < 50%;
11. Active or uncontrolled severe infection (≥CTCAE v5.0 grade 2 infection);
12. Known human immunodeficiency virus (HIV) infection. Known history of clinically significant liver disease, including viral hepatitis [Known hepatitis B virus (HBV) carriers must rule out active HBV infection, i.e., positive HBV DNA (>1×104 copies /mL or > 2000 IU/ mL); known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL);
13. Any other medical condition, clinically significant metabolic abnormality, physical abnormality or laboratory abnormality, which, in the investigator's judgment, reasonably suspects that the patient has a medical condition or condition that is not suitable for the use of the investigational drug (such as having seizures and requiring treatment), or which would affect the interpretation of the study results or place the patient at high risk;
14. The patients considered by the investigators to be unsuitable for inclusion in this study.](streamdown:incomplete-link)

Advanced gastric cancer that failed first-line treatment with PD1 antibody