Glumetinib Combined With Fruquintinib in the Treatment of MET Amplification or Protein Overexpression in Third-Line Unresectable Metastatic Colorectal Cancer

Inclusion Criteria:

1. The patients fully understood this study, voluntarily participated and signed theInformed Consent Form (ICF);

2. Age ≥18 years old;

3. Patients with unresectable metastatic colorectal cancer with microsatellite stable (MSS) confirmed by pathology or histology;

4. Have MET amplification (FISH MET GCN≥4 or MET/CEP7≥1.8; Or NGS, ≥20% of tumor cells, ≥200X sequencing depth, GCN≥4) or overexpression (IHC, 3+(≥50% of tumor cells arestrongly positive) or 2+ (≥50% of tumor cells are moderately positive/stronglypositive and < 50% of tumor cells are strongly positive); Immunohistochemistry (IHC)detection showed that the MET protein overexpression in the subjects was 3+(stronglypositive in ≥50% of tumor cells) or 2+ (positive in ≥50% of tumor cells/weaklypositive and strongly positive in < 50% of tumor cells).

5. Imaging confirmed progression after previous two-line standard anti-tumor regimens;

6. According to RECIST1.1 criteria, the patient has at least one measurable targetlesion; For lesions that have undergone radiotherapy in the past, they can only beincluded in measurable lesions when there is clear disease progression afterradiotherapy.

7. Eastern Cooperative Oncology Group (ECOG) Physical Status Score: 0-1 point;

8. The expected survival time is ≥3 months;

9. Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥75×10^9/L andhemoglobin 80 g/L, white blood cell count (WBC) ≥3.0×10^9/L (corrected by no bloodtransfusion, no blood products, no use of granulocyte colony-stimulating factor orother hematopoietic stimulating factor within 14 days before laboratory tests);

10. Liver and kidney functions: Serum creatinine ≤1.5 times the upper limit of normalvalue or creatinine clearance rate ≥50mL/min; AST and ALT ≤2.5 times the upper limitof normal values (for patients with liver invasion, ≤5 times the upper limit ofnormal values); Serum total bilirubin ≤2 times the upper limit of normal value (forpatients with liver invasion ≤2.5 times the upper limit of normal value);

11. The activated partial thromboplastin time (APTT), International normalized ratio (INR), and prothrombin time (PT) are ≤1.5 times the normal upper limit value.

12. Women of childbearing age must undergo a pregnancy test (serum) within 7 days beforeenrollment, with a negative result, and be willing to use appropriate contraceptivemethods (such as intrauterine devices [IUD], contraceptives or condoms) during thetest and 6 months after the last administration of the test drug; The serumpregnancy test must be negative within 7 days before enrollment in the study, andthe subjects must be non-lactating. Male subjects who should agree thatcontraceptive measures must be adopted during the study period and within 6 monthsafter the end of the study period;

Exclusion Criteria:

Have received MET inhibitor treatment in the past; 2. Patients with unresectable metastatic colorectal cancer who have MSI-H/dMMR (MSI detection shows instability at two or more sites, and MMR detection shows loss of expression at any one protein); 3. Patients with unresectable metastatic colorectal cancer whose BRAF gene test is mutant and who have not received BRAF inhibitors /MEK inhibitors; 4. Patients with severe active bleeding, active peptic ulcers, unhealed gastrointestinal perforations, and peptic fistulas; 5. Have hypersensitivity reactions to any investigational drug or its components; 6. Concurrent severe and uncontrolled concurrent infections or other severe and uncontrolled concomitant diseases, moderate or severe renal injury; (such as progressive infection, uncontrollable hypertension, diabetes, etc.) 7. Infection during the active stage of hepatitis B and C (positive hepatitis B virus surface antigen and hepatitis B virus DNA exceeding 1 × 103 copies /mL; Hepatitis C virus RNA exceeds 1 × 103 copies /mL; 8. Human immunodeficiency virus (HIV) infection (HIV antibody positive); 9. Have had or are currently suffering from other malignant tumors simultaneously (except for effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment in the past five years); 10. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures; 11. Those with other malignant tumors requiring treatment; 12. The researchers judged that patients were not suitable to participate in this study.