Colorectal cancer
Conditions
Interventions
Experimental Group:Aipalolitovorelizumab (QL1706) injection at a dose of 5mg/kg, administered intravenously on Day 1 of each 3-week treatment cycle.
Fruquintinib at a dose of 5mg per day, taken orally
Sponsors
Harbin Medical University Affiliated Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all of the following conditions to be enrolled in this study: 1. Have fully understood this research and voluntarily signed the informed consent form; 2. Age >=18 years old; 3. The patient must be pathologically confirmed to have advanced, metastatic or recurrent microsatellite stable (MSS) colorectal cancer (immunohistochemistry, PCR or NGS testing can be used according to the testing standards of each institution's testing center). 4. The patient's genetic test result shows no POLD1/POLE type mutation. 5. At least one immune marker is positive: (1) The PD-L1 CPSa score is >=10 points, and the tumor-infiltrating CD8+T cells are positive. (2) TMBc>=10Muts/mb, and the tumor-infiltrating CD8+T cells are positive; (3) Functional mutations in epigenetic genes such as dARID1A, KMT2A/B/C/D, and TET1/2/3, with positive tumor-infiltrating CD8+T cells; (4) Positive tertiary lymphoid structure (TLS) e exists in the tumor microenvironment 6. Patients who have previously received two or more treatment regimens for advanced or metastatic colorectal cancer, at least one of which includes fluorouracil, or who have previously received one treatment regimen for advanced or metastatic colorectal cancer and cannot tolerate second-line standard chemotherapy regimens; 7. ECOG physical condition: 0-1 point, and no deterioration within 7 days; 8. Expected survival =3 months; 9. The functional level of organs must meet the following requirements: (1) Sufficient bone marrow reserve: The absolute value of neutrophils is >=1.5 × 109/L, and that of platelets is >=90 × 10^9/L. Hemoglobin >=9g/dL; No blood transfusion or use of blood products within 14 days; (2) Liver: Plasma albumin >=2.8g/dL; Bilirubin =50%; (5) Coagulation: Prothrombin time (PT) <=1.5*ULN, International normalized ratio (INR) <=1.5*ULN, activated partial thromboplastin time (aPTT) <=1.5*ULN; (6) Thyroid stimulating hormone (TSH)<=ULN (If abnormal, the levels of FT3 and FT4 should be examined simultaneously. If the levels of FT3 and FT4 are normal, the patient can be enrolled.) 10. Women of childbearing age should take effective contraceptive measures. 11. Good compliance and cooperation with follow-up visits; 12. Agree to provide sufficient previously stored tumor tissue specimens for testing.
Exclusion criteria
Exclusion criteria: 1. Inability to adhere to the study protocol or procedures; 2. Pregnancy or lactation; 3. Any factor affecting oral administration; 4. Prior immunotherapy and fruquintinib treatment; 5. Any of the following complications: uncontrolled hypertension, coronary artery disease, arrhythmia, or heart failure; 6. Participation in another drug clinical trial within 4 weeks prior to enrollment; 7. Alcohol or drug abuse within 4 weeks of the last clinical trial; 8. Failure to discontinue anti-infective therapy within 14 days prior to study start; 9. Severe, uncontrolled systemic disease, such as severe active infection; 10. Urinalysis showing proteinuria >++, confirmed as 24-hour urine protein >1.0 g; 11. Active bleeding within 3 months; serious arterial/venous thrombotic events within 6 months; hereditary or acquired bleeding (e.g., coagulation disorders); major surgery (excluding biopsy, polypectomy), incomplete wound healing, or major trauma within 4 weeks prior to the study; aspirin (>325 mg/day) or currently or recently using dipyridamole, clopidogrel, and citrazol (10 days prior to the study); 12. Acute myocardial infarction, acute coronary syndrome, or coronary artery bypass grafting within 6 months prior to initial treatment; 13. Use of systemic glucocorticoids or other systemic immunosuppressants within 2 weeks prior to treatment. Immunosuppressants have been started or are expected to be used during the trial. For inhaled corticosteroids, physiological replacement doses are permitted; 14. Fractures or long-term unhealed wounds; 15. Received an inactivated vaccine within 4 weeks prior to enrollment; 16. Had other malignant tumors within 5 years prior to enrollment, excluding basal cell or squamous cell carcinoma of the skin after radical surgery, or cervical carcinoma in situ; 17. Known HIV infection or positive syphilis test, or known HIV-positive patient; 18. Previously received allogeneic bone marrow transplant or organ transplant; 19. Subjects allergic to the investigation drug or any of its adjuvants; 20. Electrolyte abnormalities deemed clinically significant by the investigator; 21. Detectable untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA >2000 IU/mL) or HCV carriers with detectable HCV RNA. Notes: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 2000 IU/mL) may be included in the study; 22. Previous history of radiation pneumonitis or chest CT scan showing active pneumonia within 4 weeks prior to the study; 23. The patient has an autoimmune disease requiring intervention; 24. With brain metastases, or with severe malignant pleural or peritoneal effusion; 25. Any other disease, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory abnormalities that, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for use of the study drug (e.g., seizures requiring treatment), or that will affect the interpretation of study results, or put the patient at high risk; 26. Patients deemed unsuitable for inclusion in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival;Total Survival;Disease control rate; | — |
Countries
China
Contacts
Public ContactYanqiao Zhang
Harbin Medical University Affiliated Cancer Hospital
Outcome results
None listed