Fruquintinib Combined With TAS102 for Advanced Gastric Cancer

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 advancedgastric 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 recurrencewithin 6 months after the end of treatment.
5. Measurable lesions that meet RECIST 1.1 criteria.
6. Have adequate organ and bone marrow function, laboratory tests meet the followingrequirements:
7. HGB≥90g/L;
8. NEUT≥1.5×10^9/L;
9. PLT ≥80×10^9/L;
10. TBIL≤1.5 times upper limit of normal value (ULN);
11. ALT and AST≤2.5 x ULN; In liver metastasis, ALT and AST≤5×ULN;
12. Endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula);
13. Urinary protein < (++), or 24-hour urinary protein volume < 1.0 g.
14. Normal coagulation function, no active bleeding
15. International standardized ratio INR≤1.5;
16. Partial thromboplastin time APTT≤1.5 ULN.
17. 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 ofcontraception during the observation period and within 8 weeks after the last dose ofthe study drug; For men, they should be surgically sterilized or consent to anappropriate method of contraception during the observation period and for 8 weeksafter the last administration of the study drug.
18. Expected survival ≥3 months.
19. Patients voluntarily joined the study and signed an informed consent form (ICF).
20. It is expected that the compliance is good, and the efficacy and adverse reactions canbe 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 paclitaxeltherapy in neoadjuvant or adjuvant therapy, and the treatment ended more than 6 monthsafter the disease progression);
3. Receive live vaccine within 4 weeks prior to enrollment or possibly during the studyperiod;
4. Had active autoimmune disease or history of autoimmune disease within 4 weeks prior toenrollment;
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 thepatient could not take drugs orally;
8. Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerativecolitis, or active bleeding of unexcised tumors, or other conditions that may causegastrointestinal bleeding or perforation as determined by researchers beforeenrollment;
9. Patients with evidence or history of significant bleeding tendency within 3 monthsprior to enrollment (bleeding within 3 months > 30 mL, hematemesis, stool, stoolblood), hemoptysis, or thromboembolic events (including stroke events and/or transientischemic attacks) within 12 months;
10. Clinically significant cardiovascular disease, including but not limited to acutemyocardial infarction, severe/unstable angina pectoris, or coronary artery bypassgrafting within 6 months prior to enrollment; New York Heart Association (NYHA) Gradesfor Congestive Heart Failure > Level 2; Ventricular arrhythmias requiring medicaltreatment; 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 clinicallysignificant 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, physicalabnormality or laboratory abnormality, which, in the investigator's judgment,reasonably suspects that the patient has a medical condition or condition that is notsuitable for the use of the investigational drug (such as having seizures andrequiring treatment), or which would affect the interpretation of the study results orplace the patient at high risk;
14. The patients considered by the investigators to be unsuitable for inclusion in thisstudy.