A Study to Explore the Third-line Treatment of Fruquintinib Combined With Serplulimab in Advanced Non-liver-limited Metastatic Colorectal Cancer: a Single-center, Phase 2 Study
The aim of this clinical trial is to learn about efficacy of fruquintinib combined with serplulimab in patients with microsatellite stabilized mCRC who have failed standard therapy. The main purpose is to explore efficacy, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including ctDNA, TPS, CPS, tumor mutation burden, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, etc.) and the efficacy and drug resistance mechanism will be analyzed, which could provide reference for determining the advantaged group.
• Age ≥18 years old, both sexes;
• Patients with histologically or cytologically confirmed unresectable and metastatic CRC
• non-liver-limited metastasis: including no liver metastasis or liver metastasis accompanied by other metastatic lesions, such as lung metastasis, peritoneal metastasis, etc
• Before enrollment, the tumor tissue was pMMR by immunohistochemistry, or MSS or MSI-L by PCR or NGS;
• Have received standard treatment in the past and developed disease progression or intolerance to standard treatment based on RECIST 1.1 during or after standard treatment. Standard treatment should include:
‣ Fluorouracil, oxaliplatin and irinotecan
⁃ With or without anti-VEGF monoclonal antibody
⁃ For RAS wild-type patients, combined with anti-EGFR monoclonal antibody
⁃ For patients with BRAF mutations, BRAF inhibitor therapy is recommended when drugs are available
• Patients with ECOG score of 0-2 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy;
• At least one measurable tumor lesion according to RECIST 1.1 criteria
• Good organ function:
‣ neutrophil ≥1.5\*109/L; Platelet ≥100\*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl;
⁃ Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range;
⁃ bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal;
⁃ Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥60ml/min;
⁃ International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the upper limit of the normal range, unless the patient is receiving anticoagulant therapy and the PT value is within the intended range for anticoagulant therapy;
⁃ Activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of normal;
• There were no serious concomitant diseases that could make the survival time less than 5 years;
• Negative pregnancy test in female subjects (for female patients of childbearing potential); Infertile female patients;
• Male patients of childbearing potential and female patients of childbearing potential and at risk of pregnancy must agree to use adequate contraception for the entire duration of the study and for 12 months after receiving treatment with the protocol;
• Signed and dated informed consent indicating that the patient has been informed about all relevant aspects of the study;
• Patients who are willing and able to comply with the visit schedule, treatment plan, laboratory tests, and other study procedures;
• Willing to comply with the arrangement during the study period can not participate in any other clinical research on drugs and medical devices