Metastatic colorectal cancer
Conditions
Interventions
Treatment group:Iparomlimab and Tuvonralimab combined with anti-angiogenic drugs
Sponsors
Sichuan Provincial People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign a written ICF; 2. Age >=18 years old, = 3 months; 5. Subjects with histologically or cytologically confirmed metastatic colorectal adenocarcinoma; 6. Patients with colorectal cancer who are not suitable for radical surgical resection or local treatment, and who have received second-line or above systemic anti-tumor therapy; 7. According to RECIST v1.1, at least one measurable lesion, and the lesion is suitable for repeated accurate measurement, Note: Brain metastasis lesion cannot be used as a target lesion; If no other lesion meets the target lesion criteria, the lesion that has undergone radiotherapy can be considered as a target lesion when it can be measured according to RECIST v1.1 and there is objective evidence of significant progression after radiotherapy; 8. Subjects are required to provide 15 recently dated archived or freshly obtained FFPE pathological sections of tumor tissue. 9. Good organ function as determined by the following requirements: (1) Hematology (no use of any blood components and cell growth factor supportive therapy within 7 days prior to starting study treatment): 1) Absolute neutrophil ANC >= 1.5 ×10^9/L (1,500/mm^3); 2) Platelet count >= 100 × 10^9/L (100,000/mm^3); 3) Hemoglobin >= 90 g/L; (2) Kidneys: 1) Creatinine clearance* (CrCl) calculated value >= 50 mL/min or Cr=28 g/L; (4) Coagulation function: 1) International normalized ratio and activated partial thromboplastin time =50%; 10. Female subjects of childbearing potential must undergo a urine or serum pregnancy test within 3 days prior to the first dose of the study drug (if the urine pregnancy test cannot confirm a negative result, a serum pregnancy test is required, and the serum pregnancy result shall prevail), and the result must be negative. If a female subject of childbearing potential has sexual intercourse with a male partner who is not surgically sterile, the subject must use an acceptable contraceptive method starting from the screening and must agree to continue using contraception for 6 months after the last dose of the study drug; whether to discontinue contraception after this period should be discussed with the investigator. 11. If a male subject who is not surgically sterile has sexual intercourse with a female partner of childbearing potential, the subject must use an effective contraceptive method from screening until 6 months after the last dose; whether to discontinue contraception after this period should be discussed with t
Exclusion criteria
Exclusion criteria: 1. Patients with known MSI-H or dMMR; 2. Subjects have other malignant tumors within 3 years prior to enrollment, except for cured localized tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.); 3. Enrollment in another clinical study at the same time, unless it is an observational, non-interventional clinical study or follow-up period of an interventional study; 4. Received systemic anti-tumor therapy (chemotherapy) within 3 weeks prior to the first dose; Palliative local therapy for non-target lesions within 2 weeks prior to the first dose; Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymuspein, etc., excluding IL-11 for the treatment of thrombocytopenia) within 2 weeks before the first dose; Have received Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 1 week before the first dose; 5. Previous immuno-anti-tumor therapy, including immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy, and any other treatment targeting the mechanism of tumor immune action; 6. Active autoimmune disease (e.g., treatment with modifying drugs, corticosteroids, immunosuppressants) that required systemic treatment within the past two years, replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) that is not considered a systemic treatment; 7. Active or previous history of definite inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea); 8. History of immunodeficiency; Those who test positive for HIV antibodies; Current long-term use of systemic corticosteroids or other immunosuppressants; 9. Subjects with known active tuberculosis (TB) and suspected active TB need to be excluded by clinical examination; Known active syphilis infection; 10. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 11. Previous or current non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy; 12. Serious infection within 4 weeks prior to the first dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infection with systemic anti-infective therapy within two weeks prior to the first dose (excluding antiviral therapy for hepatitis B or hepatitis C); 13. Subjects with current active hepatitis B (HBsAg positive and HBV-DNA greater than 5000 copies/ml (1000 IU/ml) or above the lower limit of detection, whichever is higher). Note: For subjects with hepatitis B, anti-hepatitis B virus therapy is required during study treatment; 14. Active hepatitis C subjects (positive for HCV antibody and HCV-RNA level above the lower limit of detection); 15. Major surgical procedure or severe trauma within 30 days prior to the first dose, or planned major surgical procedure within 30 days after the first dose (as determined by the investigator); Minor local surgery (excluding transperipheral venipuncture central venous catheterization and intravenous port implantation) within 3 days prior to the first dose; 16. Presence of active central nervous system (CNS) metastases. Note: Subjects with previously treated brain metastases (e.g.,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progress free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response;safety;Objective response rate;overall survival;Disease control rate;Time to response; | — |
Countries
China
Contacts
Public ContactLiu Hao
Sichuan Provincial People's Hospital
Outcome results
None listed