Ivosidenib Plus mFOLFOXIRI and Celecoxib for BRAF-targeted Therapy-refractory BRAF V600E-mutant Colorectal Cancer Patients

Inclusion Criteria: 1. Signed the informed consent form voluntarily. 2. Aged 18-70. 3. Colorectal adenocarcinoma with definite histological evidence, with evidence of distant metastasis; 4. Diagnosed with colon or rectal adenocarcinoma, with evidence of distant metastasis; 5. Genetic testing indicates a BRAF V600E mutation; 6. Previously received first-line treatment including FOLFOX/CAPOX or FOLFIRI/CAPIRI and experienced disease progression or intolerance. Among them, patients who used oxaliplatin in adjuvant therapy should have experienced disease progression within 12 months after completing adjuvant therapy; Previously received anti-BRAF V600E targeted therapy and failed, including but not limited to vemurafenib, dabrafenib, and encorafenib; 7. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. 8. Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment: neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2.5×UNL, alanine transferase ≤2.5×UNL, serum creatinine ≤2.5×UNL; 9. Female subjects must be either postmenopausal for at least 1 year, have undergone surgical sterilization at least 6 weeks prior, or must agree to use appropriate contraceptive measures; 10. Male subjects must agree to use appropriate contraceptive measures to prevent their partners from becoming pregnant; 11. Willing and able to comply with research protocols and visit plans. Exclusion Criteria: 1. Prior to enrollment, ctDNA testing shows known KRAS mutation, NRAS mutation, or ERBB2 gene amplification; tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability, KRAS mutation, NRAS mutation, or ERBB2 gene amplification; 2. Presence of intestinal obstruction, active bleeding, or intestinal perforation requiring emergency intervention; 3. Underwent major surgery or severe trauma in the previous 4 weeks; 4. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months prior to study participation; 5. Occurrence of thrombotic or embolic events within the past 6 months; 6. New York Heart Association (NYHA) class II or higher congestive heart failure; 7. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis; 8. Any active, known, or suspected autoimmune disease. 9. Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic disease; 10. Any unresolved treatment-related adverse events of grade 2 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (excluding peripheral neuropathy, anemia, hair loss, and skin pigmentation); 11. Previous treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies; 12. Known or suspected history of allergy to any of the related drugs used in the study; 13. Pregnant or breastfeeding women.