A Single-arm, Multicenter Clinical Study of Fruquintinib Combined With Serplulimab and Chemotherapy as First-line Treatment for Patients With RAS/BRAF-mutated Advanced Colorectal Cance

Prior treatment

• Major surgery or severe trauma within 4 weeks prior to first study drug administration.
• Current use of immunosuppressive agents, or systemic or absorbable local hormone therapy for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent), and continued use within 2 weeks before enrollment.
• Known inherited or acquired bleeding/thrombotic tendency (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.) or currently receiving thrombolytic or anticoagulant therapy.

Other illness

• \- History of hypersensitivity to any anti-angiogenic targeted agent, any component of monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs.
• Presence of any active autoimmune disease or history of autoimmune disease.
• History of other malignancies within the past 5 years, except for radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Currently active bleeding or significant bleeding tendency within 3 months (i.e., patients at high risk of bleeding).

Other

• Untreated central nervous system (CNS) metastases.

• 18 to 75 years (inclusive), male or female.
• Diagnosis of advanced unresectable or metastatic colorectal cancer.
• Confirmed RAS/BRAF mutation by testing.
• No prior systemic therapy for unresectable or metastatic colorectal cancer. (Prior adjuvant or neoadjuvant chemotherapy with one regimen is allowed if recurrence occurred ≥6 months after completion of chemotherapy.)
• ECOG 0 - 1.
• Adequate major organ and bone marrow function (without any blood component or cell growth factor support within 14 days before enrollment):
  • Hematology: absolute neutrophil count ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, hemoglobin ≥90 g/L.
  • International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
  • Liver function: total bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (≤5 × ULN in patients with liver metastases).
  • Renal function: serum creatinine ≤1.5 × ULN, and creatinine clearance (CCr) ≥50 mL/min.
• Female patients of childbearing potential must have a negative serum pregnancy test within 14 days before treatment. Fertile patients (male and female) must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence) with their partners during the study and for at least 6 months after the last dose