A Prospective, Open-label, Single-arm Phase II Clinical Study of Fruquintinib Combined With S-1 for the Treatment of Metastatic Colorectal Cancer.

Inclusion Criteria:

1. Fully understand this study and voluntarily sign the informed consent form;

2. Age ≥18 years, gender not limited;

3. Confirmed advanced metastatic colorectal adenocarcinoma by histopathologicalexamination;

4. Patients have previously received at least one line of standard therapy containingfluorouracil, oxaliplatin, and irinotecan, and have progressed or are intolerant.

• Each line of treatment must include one or more chemotherapy drugs for aduration of ≥1 cycle;

• Adjuvant/neoadjuvant therapy is allowed. If recurrence or metastasis occursduring or within 6 months after completion of adjuvant/neoadjuvant therapy, itis considered a failure of first-line chemotherapy for progressive disease;

• Prior use of chemotherapy combined with cetuximab or bevacizumab in antitumortreatment regimens is allowed;

5. At least one measurable lesion (RECIST 1.1 criteria);

6. ECOG performance status 0-1;

7. Expected survival time ≥12 weeks;

8. Within 14 days before enrollment, the function of major organs must meet thefollowing requirements (no use of any blood components and cell growth factorswithin 14 days before enrollment):

• Absolute neutrophil count ≥1.5×10^9/L;

• Platelet count ≥80×10^9/L;

• Hemoglobin ≥8g/dL;

• Total bilirubin <1.5 times the upper limit of normal (ULN);

• ALT and AST <2.5 times ULN (<5 times ULN for patients with liver metastasis);

• Serum creatinine ≤1 times ULN;

• Endogenous creatinine clearance rate >50ml/min;

9. Women of childbearing age or men with partners who wish to have children must useeffective contraceptive measures;

10. Agree to provide blood samples.

Exclusion Criteria:

1. Have previously received treatment with fruquintinib or other anti-VEGFR (vascularendothelial growth factor receptor) inhibitors such as apatinib, regorafenib, andanlotinib;

2. Have previously received treatment with tegafur;

3. Have participated in another drug clinical trial within four weeks before enrollmentand received at least one dose of medication, or have received other systemicantitumor treatments, including chemotherapy, signal transduction inhibitors,hormone therapy, and immunotherapy within four weeks before enrollment;

4. Patients currently have diseases or conditions that affect drug absorption, orpatients are unable to orally take fruquintinib;

5. Patients currently have active gastric and duodenal ulcers, ulcerative colitis, andother gastrointestinal diseases, or have active bleeding from unresected tumors, orother conditions that may cause gastrointestinal bleeding or perforation as judgedby the investigator;

6. Have active bleeding or bleeding tendencies;

7. Have uncontrollable malignant pleural effusion, ascites, or pericardial effusion (defined as not effectively controlled by diuretics or puncture as judged by theinvestigator);

8. Have a history of severe cardiovascular and cerebrovascular diseases:

• Cerebral vascular accidents (except for lacunar infarction, minor cerebralischemia, or transient cerebral ischemic attacks), myocardial infarction,unstable angina, poorly controlled arrhythmias (including QTc interval formales ≥ 450ms, females ≥ 470ms) (QTc interval calculated using the Fridericiaformula) within 6 months before the first dose of the study drug;

• New York Heart Association (NYHA) heart function classification > II or leftventricular ejection fraction (LVEF) < 50%;

9. Have had other malignancies in the past 5 years, except for skin basal cell orsquamous cell carcinoma after radical surgery, or cervical carcinoma in situ;

10. Have clinically uncontrolled active infections, such as acute pneumonia, activehepatitis B or C (history of hepatitis B virus infection not under drug control, HBVDNA ≥1×10^4 copies/mL or >2000 IU/mL);

11. Have clinically symptomatic central nervous system metastases and/or meningealcarcinomatosis;

12. Patients currently have uncontrolled hypertension with medication, defined as:systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg aftertaking antihypertensive drugs;

13. Urinalysis indicates urinary protein ≥2+, and re-examined 24-hour urinary proteinquantity >1.0g;

14. Pregnant (positive pregnancy test before medication) or breastfeeding women;

15. The investigator judges that there are clinically significant severe electrolyteabnormalities, or the investigator believes that the patient is unsuitable forparticipation in this clinical study for other reasons.