A Multicenter, Prospective, Phase II Exploratory Study on the First-line Treatment of MSS/ PMMR-type Advanced Colorectal Cancer With Adebrelimab Combined With Simvastatin and Targeted and Chemotherapy
Metastatic colorectal cancer with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) molecular phenotypes could significantly benefit from immune checkpoint inhibitor therapy, ushering in the MSI era of immunotherapy for colorectal cancer. However, MSI-H/dMMR is present in only 15%-20% of stage II/III and 5% of stage IV colorectal cancer patients, while the vast majority of patients exhibit microsatellite stability (MSS) or proficient mismatch repair (pMMR) types, which are insensitive to immunotherapy. Therefore, how to enhance the efficacy of immunotherapy in the pMMR/MSS population through combination therapy has become a hotspot and challenge in colorectal cancer research.
• Able to provide written informed consent and voluntarily participate in this study.
• Male or female subjects aged between 18 and 75 years, inclusive.
• Histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
• No prior systemic anti-tumor therapy; patients who have received neoadjuvant/adjuvant therapy are eligible if the time from the last chemotherapy to recurrence or progression is more than 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of at least 3 months.
• Presence of at least one measurable lesion at baseline assessed by the investigator according to RECIST 1.1. Measurable lesions must not have been previously treated with radiotherapy or other local therapy, unless the lesion located in a previously irradiated area has been confirmed to have progressed.
• Adequate organ function as defined below (no blood products or hematopoietic growth factors are allowed within 14 days prior to the first dose of study treatment):
‣ Absolute neutrophil count (ANC) ≥1.5×10\^9/L
⁃ Platelet count ≥100×10\^9/L
⁃ Hemoglobin ≥9 g/dL
⁃ Serum albumin ≥2.5 g/dL
⁃ Total bilirubin ≤1.5 × ULN; ALT and AST ≤2.5 × ULN, or ≤5 × ULN in the presence of liver metastases
⁃ Serum creatinine ≤1.5 × ULN, or creatinine clearance \>60 mL/min (calculated by Cockcroft-Gault formula)
⁃ Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5 × ULN. Subjects receiving stable-dose anticoagulation such as low molecular weight heparin or warfarin with INR within the expected therapeutic range are eligible.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment, must not be breastfeeding, and must agree to use effective contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study and for at least 6 months after the last dose of study treatment. Male subjects with partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 3 months after the last dose of study treatment, and must not donate sperm during the study period.