Efficacy and Safety of Tunlametinib Combination Therapy in the Treatment of Second-line and Above Metastatic Colorectal Cancer

This study investigated the efficacy and safety of Tunlametinib Combination Therapy in the Treatment of Second-line and Above Metastatic Colorectal Cancer.

Inclusion Criteria: * Age ≥ 18 years of age, both genders. * ECOG, 0-1. * Patients with metastatic colorectal cancer confirmed by histology or cytology * Previous genetic test results can determine the gene status (mutation or wild type) of the RAS/RAF/MEK/ERK pathway (MAPK pathway), and the results of genetic testing or immunohistochemical testing can confirm whether it is MSS/pMMR or MSI-H/dMMR (if MSI-H/dMMR has been treated with PD-1 antibody, only the A cohort (MEK inhibitor + EGFR monoclonal antibody cohort) can be screened; if MSI-H/dMMR has not been treated with PD-1 antibody, the B cohort (MEK inhibitor + EGFR monoclonal antibody + PD-1 monoclonal antibody cohort) can be screened; if BRAF V600E mutation is present, the B cohort or C cohort (MEK inhibitor + EGFR monoclonal antibody / BRAF inhibitor + PD-1 monoclonal antibody cohort) can be screened). * Patients were required to have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). * Previous treatment with at least one line of standard therapy failed (disease progression or intolerable side effects), and the patient is scheduled to receive ≥ 2 lines of treatment; for neoadjuvant or adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after discontinuation of treatment, it should be counted as the first line of treatment (assessed by the investigator according to RECIST 1.1); * The life expectance should be at least 3 months. * To ensure eligibility, the following criteria must be met regarding major organ and bone marrow functions: 1. . Hematological Parameters: A complete blood count must indicate hemoglobin levels of ≥90 g/L (with no blood transfusions administered within the preceding 14 days), an absolute neutrophil count of ≥1.5 × 10⁹/L, and a platelet count of ≥100 × 10⁹/L. 2. . Liver Function: Liver function tests should reveal alanine aminotransferase (ALT) levels ≤2.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) levels ≤2.5 × ULN, total bilirubin levels ≤1.5 × ULN, and albumin levels ≥30 g/L. In cases where liver metastases are present, ALT and AST levels may be elevated to ≤5 × ULN, while total bilirubin must remain ≤1.5 × ULN. 3. . Renal Function: Renal function should be assessed with serum creatinine levels ≤1.5 × ULN or a creatinine clearance, calculated using the Cockcroft-Gault formula, of \>60 mL/min. 4. . Cardiac Function: Cardiac assessment via echocardiography should indicate a left ventricular ejection fraction (LVEF) of ≥55%. Additionally, the corrected QT interval (QTcF) on electrocardiogram should be ≤480 ms, with creatine kinase (CK) levels ≤1 × ULN and troponin or high-sensitivity troponin levels ≤1 × ULN. 5. . Coagulation Function: Coagulation parameters must include an international normalized ratio (INR) of ≤1.5 × ULN and activated partial thromboplastin time (APTT) of ≤1.5 × ULN. 6. . Urinalysis: Urinalysis should demonstrate urine protein levels of \