Gossypol Acetate + FOLFIRI + Bev in mCRC With TP53-Mutant and LRPPRC Positive

Inclusion criteria

• Female patients aged ≥18 years.
• Histopathologically or cytologically confirmed adenocarcinoma of the colon or rectum.
• Radiologically confirmed unresectable metastatic disease.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Prior first-line treatment with an oxaliplatin-based regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy ≥3 months.
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥100×10⁹/L, hemoglobin (Hb) ≥90 g/L, and white blood cell count (WBC) ≥3.0×10⁹/L.
• Adequate liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤2.5 × the upper limit of normal (ULN), or ≤5×ULN in the presence of liver metastases; total bilirubin ≤1.5×ULN.
• Adequate renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula), and urine protein <2+.
• Normal coagulation function: international normalized ratio (INR) ≤1.5.
• Ability to understand the study requirements; voluntary provision of written informed consent by the patient and/or legal representative.

Exclusion criteria

• Patients with a history of other malignant tumors within the past 5 years (except cured carcinoma *in situ* or basal cell carcinoma of the skin).
• Patients previously subjected to irinotecan or irinotecan liposome-based chemotherapy.
• Presence of massive pleural effusion or ascites requiring therapeutic intervention.
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic treatment, defined as persistent signs/symptoms related to the infection without improvement despite appropriate antibiotic, antiviral, and/or other therapy.
• Known active HIV infection (i.e., positive for HIV-1/2 antibodies); untreated active HBV infection (defined as positive for HBsAg or HBcAg with detectable HBV-DNA copies exceeding the upper limit of normal [ULN] at the local laboratory) and active HCV infection (positive for HCV antibody with an HCV-RNA level above the ULN).
• Concurrent uncontrolled systemic diseases, including cardiovascular disorders such as unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmias, or a history of severe pericardial disease; uncontrolled hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg after standardized antihypertensive therapy) or a history of hypertensive crisis or hypertensive encephalopathy; uncontrolled diabetes mellitus, etc.
• Presence of severe gastrointestinal diseases (including active bleeding, obstruction greater than Grade 1, diarrhea greater than Grade 1, or gastrointestinal perforation).
• History of laparotomy, thoracotomy, or intestinal resection within 28 days prior to enrollment.
• Presence of interstitial lung disease or pulmonary fibrosis.
• Known allergy or intolerance to the investigational drug(s) or their excipients.
• History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as at least 2.5 mL of bright red blood) within one month prior to enrollment.
• History of arterial thromboembolism, severe hemorrhage (excluding bleeding due to surgery), or current predisposition to embolism or severe hemorrhage within 6 months prior to enrollment.
• Presence of central nervous system metastases.
• Serum albumin level ≤ 3 g/dL.
• Concomitant use of strong inhibitors or inducers of CYP3A4, CYP2C8, or UGT1A1.
• Pregnant or lactating women, as well as patients of childbearing potential who refuse to adopt adequate contraceptive measures during the trial.
• Participation in another clinical trial within 30 days prior to the first dose of the investigational drug.
• Allergy to bevacizumab, irinotecan, fluorouracil, calcium folinate, or compound gossypol acetate tablets.
• Patients deemed by the investigator to be unsuitable for participation in this study.