The Efficacy and Safety of IBI351, Cetuximab β Combined With FOLFIRI as First-line /IBI351, Cetuximab β as Second-line in the Treatment of KRAS G12C-mutated Metastatic Colorectal Cancer

Who may be able to join

• The following conditions must be met:
• On the day of signing the informed consent form, the age should be ≥18 years old (18-75 years old, including 18 and 75 years old).
• 2. The patient must have histologically and/or cytologically confirmed metastatic colorectal cancer (stage IV) 3. There is a written test report proving the presence of KRASG12C mutation: PCR method or NGS method detection clearly indicates KRASG12C mutation 4. Cohort A: Untreated advanced metastatic colorectal cancer; Cohort B: Advanced metastatic colorectal cancer with disease progression after first-line standard chemotherapy (FOLFOX,FOLFIRI,XELOX, FOLFOXIRI± targeted therapy) 5. There are measurable lesions according to the Recist 1.1 standard 6.ECOG PS 0-1 7. Weight ≥40Kg 8. Cardiac function test: Left ventricular ejection fraction (LVEF) ≥50%(echocardiography) 9. Life expectancy >3 months 10. Have sufficient organ functions, including:
• There is sufficient hematopoietic function, that is, the absolute neutrophil count (A NC) ≥1.5×109/L, platelet count ≥75×109/L, and hemoglobin ≥9g/d L. Blood transfusion or treatment with granulocyte colony-stimulating factor, thrombopoietin, erythropoietin, etc. shall not be received within 14 days before the blood routine test.
• Have sufficient liver function, namely total bilirubin (TBIL) < 1.5× upper limit of normal value (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (A LT) < 2.5×ULN; If one has Gilbert syndrome, the total bilirubin is less than 2×ULN. If it is liver metastasis of the tumor, the AST and ALT should be less than 5.0×ULN. If direct bilirubin (DBIL) indicates extrahepatic obstruction, TBIL < 3.0×ULN is allowed.
• Have sufficient renal function, that is, creatinine (Cr) ≤1.5×ULN, or when Cr > 1.5×ULN, the creatinine clearance rate (CrCl) calculated using the Cockcroft-Gault formula (see Appendix 5) ≥50 mL/min. Urine protein/creatinine ratio < 1 (or urine analysis < 1+ or 24-hour urine protein < 1g/24 h)
• It has sufficient coagulation function, that is, prothrombin time (PT) and activated partial thromboplastin time (APTT) < 1.5×ULN, and the international normalized ratio (INR) < 1.5 or is within the target range of anticoagulant therapy 11. The toxic reactions of previous anti-tumor treatments need to be restored to the baseline level (except for the residual alopecia effect) or ≤ grade 1 before enrollment (neurotoxicity is acceptable ≤ grade 2). Immune-related Adverse Events (irAE) related to endocrine caused by previous immunotherapy, such as immune-related hypothyroidism that is controlled stably and asymptomatic after treatment, still require stable doses of hormone replacement or physiological doses of corticosteroids for treatment. After the researcher assesses that it does not affect the administration of the study drug and conducts a safety assessment, they can be enrolled 12. Have the ability to take oral medication 13. Fertile female or male subjects must agree to adopt effective contraceptive methods from the date of signing the informed consent form until 30 days after the last administration of IBI351 or 60 days after the last administration of cetuximab. The blood pregnancy test results of fertile female subjects within 7 days (inclusive) before administration should be negative 14. Understand and sign the informed consent form The researchers judged that the subjects could communicate well, be followed up on schedule, and complete the study in accordance with the provisions of the protocol-