A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer

Inclusion criteria

• Aged ≥ 18 years old and ≤ 75 years old.
• Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma;
• Patients must have at least one measurable lesion according to RECIST 1.1 criteria.
• Had received first-line treatment based on oxaliplatin.
• Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
• Expected survival time ≥3 months.
• Adequate organ function, meeting the following laboratory test standards:

• Bone marrow function: Neutrophils≥1.5×109/L, Platelets≥100×109/L, Hemoglobin≥90 g/L, White blood cells ≥3.0×109/L; 2) Liver function:Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase≤2.5×upper limit of normal (ULN), when there is liver metastasis, ≤ 5×ULN; Total bilirubin≤1.5×ULN; 3) Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance rate ≥ 60 ml/min, Urine protein≤2+; 4) Coagulation function: Activated partial thromboplastin time and International Normalized Ratio ≤1.5 × ULN; 5) Thyroid function: Thyroid stimulating hormone≤ULN; If abnormal, additional tests for FT3 and FT4 should be conducted and their levels should be normal; 6) Albumin≥3 g/dL; 8. Pregnant women of childbearing age with negative pregnancy test and non-lactating, participants with reproductive capacity must receive effective contraceptive measures; 9. Patients and/or legal representative must have the ability to understand and voluntarily sign a written informed consent.

Exclusion criteria

• Patients with a history of other malignancies within the past 5 years, except for cured carcinoma in situ or basal cell carcinoma of the skin.
• Prior treatment with irinotecan or liposomal irinotecan-based chemotherapy, or prior treatment with immune checkpoint inhibitors (including but not limited to PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors).
• Patients with left-sided colorectal cancer, RAS/BRAF wild-type, who did not receive cetuximab in first-line therapy.
• Patients with known mismatch repair dysfunction or microsatellite instability ;
• Patients with a large amount of pleural effusion or ascites that require drug intervention treatment;
• Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, who show persistent signs/symptoms without improvement despite appropriate antimicrobial therapy.
• Known active HIV infection; untreated active HBV or HCV infection.
• Patients with uncontrolled systemic diseases, including: cardiac disease of NYHA Class II or above; uncontrolled hypertension (defined as systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg despite standard antihypertensive therapy) or a history of hypertensive crisis or hypertensive encephalopathy; uncontrolled diabetes mellitus; etc.
• Patients with active autoimmune diseases, or with a history of autoimmune disease within 2 years prior to enrollment that still requires systemic therapy. Exceptions include participants with well-controlled type 1 diabetes, hypothyroidism controlled with hormone replacement alone, skin disorders not requiring systemic treatment, or those in whom recurrence is not anticipated in the absence of external triggers.
• Patients with primary immunodeficiency diseases or with a history;
• Patients who have received immunosuppressant treatment within 14 days before enrollment or require daily systemic steroid treatment (such as > 20 mg/day prednisone or equivalent drugs), except those treated with nasal, inhalation or other routes of local glucocorticoid therapy;
• Patients with severe gastrointestinal diseases;
• History of abdominal surgery, thoracic surgery, or intestinal resection within 28 days prior to enrollment.
• Had interstitial lung disease or non-infectious pneumonia requiring glucocorticoid treatment;
• Known hypersensitivity or intolerance to the investigational drugs or their excipients.
• History of pulmonary hemorrhage or hemoptysis of grade 2 or higher (defined as at least 2.5 mL of bright red blood) within 1 month prior to enrollment.
• History of arterial thromboembolism, severe bleeding (excluding surgical bleeding), or active thromboembolic or severe bleeding events within 6 months prior to enrollment.
• Had symptomatic central nervous system metastasis;
• Had strong inhibitors or inducers of CYP3A4, CYP2C8 and UGT1A1;
• Receipt of intravenous antitumor therapy within 28 days, or oral antitumor medication within 14 days, prior to the first dose of study drug.
• Patients judged by the investigator to be unsuitable to participate in this study.