Evaluation of Irinotecan Liposome (II) Combined With 5-FU, LV, and Bevacizumab for mCRC

Exclusion Criteria

• •1. Have had a malignant tumor other than colorectal cancer within 5 years before the screening (cured skin basal cell or squamous cell carcinoma, cervical carcinoma in situ, and malignant tumors assessed by researchers as having a low risk of metastasis and death except);
• •2. Tumor tissue is known to have a mismatch repair defect (DMMR) status confirmed by immunohistochemistry, or a microsatellite high instability (MSI-H) status confirmed by second-generation sequencing (NGS) polymerase chain reaction (PCR) methods, they were evaluated by the investigators as being suitable for treatment with immune checkpoint inhibitors (PD-1/PD-L1 inhibitors)
• •3. The second generation sequencing (NGS)/polymerase chain reaction (PCR) method confirmed that it is a BRAF V600E mutation, which is unfavorable for patients with chemotherapy prognosis;
• •4. For those who are known to have central nervous system metastases, for patients with clinically suspected central nervous system metastases, enhanced computed tomography (CT) or enhanced nuclear magnetic resonance (MRI) must be performed within 28 days before the first medication to rule out central nervous system metastases;
• •5. Previous treatment with irinotecan/irinotecan liposome-based chemotherapy;
• •6. Use of CYP3A4, CYP2C8 and UGT1A1 strong inhibitors/strong inducers within 14 days before starting the study. 7. Participated in other drug clinical trials within 4 weeks before the first dose;
• •7. Participated in clinical trials of other drugs within 4 weeks before the first medication;
• •8. Clinical records showed severe gastrointestinal dysfunction (including bleeding and obstruction; NCI-CTCAE v5.0 \> Grade 2 inflammation; NCI-CTCAE v5.0 \> Grade 1 diarrhea)
• •9. Presence of severe comorbidities, active infections, or uncontrolled diabetes that interfere with the treatment of the trial drug: (1) uncontrolled severe medical disease that the investigators believe will affect the ability of the subject to receive treatment with the study regimen; For example, complicated with severe medical conditions, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc. (2) the occurrence of A/V thrombotic event within one year before screening, such as cerebrovascular accident (including transient ischemic attack) , thrombosis disease (except venous thrombosis caused by venous catheterization during pre-chemotherapy, which is judged to be cured by researchers) , pulmonary embolism, etc. (3) imaging showed that the tumor had invaded around the important blood vessels or the patients had a high possibility of invading the important blood vessels and causing fatal massive hemorrhage (4) the subjects had active, known or suspected autoimmune diseases including systemic lupus erythematosus, Hashimoto's thyroiditis, scleroderma, Polyarteritis nodosa or autoimmune hepatitis; Participants with type 1 diabetes, hypothyroidism requiring hormone replacement only, skin conditions that do not require systemic treatment (such as leukoplakia, psoriasis, or hair loss) , or conditions that are not expected to recur without an external trigger were allowed to participate; (5) active pulmonary tuberculosis infection. Patients with active tuberculosis infection within 1 year of treatment should be excluded, even if they have been treated, and patients with a history of active tuberculosis infection more than 1 year before should be excluded, (6) previous Interstitial lung disease, or has (non-infectious) pneumonia requiring oral or intravenous steroid hormone therapy; (7) long-term treatment with systemic sex hormones (at a dose equivalent to \> 10 mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects who used inhaled or topical corticosteroid were selected, and those who had poorly controlled cardiac clinical symptoms or conditions, such as heart failure of NYHA Class 2 or above, unstable angina, and heart failure were selected Myocardial infarction within 6 months, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, positive Hepatitis C virus antibodies to HCV or HIV; Severe infection (NCI-CTCAE v5.0 \> 2) occurred within 4 weeks before screening, such as severe pneumonia, bacteremia, infection complications, etc. The presence of symptoms and signs of infection within 2 weeks before study initiation required intravenous antibiotic therapy (except for prophylactic antibiotic use) ; (10) subjects with grade ≥2 peripheral neuropathy according to NCI-CTCAE v5.0.
• •10. Known to be allergic or intolerant to any test drug (irinotecan hydrochloride liposome injection (Ⅱ), 5-FU/LV, bevacizumab) or an excipient thereof;
• •11. There are known contraindications to any experimental drug (irinotecan hydrochloride liposome injection (Ⅱ), 5-FU/LV, bevacizumab);
• •12. Women who are pregnant, breastfeeding or have given birth but refuse to use contraception;
• •13. The researcher believes that it should be excluded from this study. For example, if the researcher judges that the subject has other factors that may lead to the forced termination of this study, such as the existence of other serious diseases (including mental illness) that require combined treatment, There are serious abnormalities in laboratory tests, accompanied by family or social factors, which will affect the safety of the subject or the collection of data and samples.