Immune Checkpoint Inhibitors + Chemotherapy Versus Chemotherapy in the Neoadjuvant Treatment of Locally Advanced Colorectal Cancer

Comparison of Immune Checkpint Inhibitors Combined With Chemotherapy Versus Chemotherapy Alone in the Neoadjuvant Treatment of Locally Advanced Colorectal Cancer: a Randomized, Open-label, Single-center Phase II Clinical Study

The goal of this clinical trial is to compare the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and FOLFOX regimen compared to FOLFOX regimen alone in the neoadjuvant chemotherapy of locally advanced colorectal cancer. The main question aims to answer are:

Question 1: Compare the pathological complete response rate between the combination of ICIs and FOLFOX regimen and the FOLFOX alone.

Question 2: Compare the survival outcomes and safety between the combination of ICIs and FOLFOX regimen and the FOLFOX alone.

Two groups of participants will receive different new adjuvant chemotherapy regimens, and their efficacy will be compared.

A prospective, randomized, open, multi-center clinical study evaluating the efficacy (pathological response, survival outcomes) and safety of the combination of ICIs and FOLFOX regimen compared to FOLFOX regimen in the treatment of locally advanced colorectal cancer.

Inclusion Criteria:

• Age 18 to 75, no gender restrictions;
• Histologically or cytologically confirmed colorectal adenocarcinoma;
• Clinically diagnosed as stage II/III colorectal cancer based on CT and/or MRI (according to the 8th edition of AJCC staging);
• Sufficient tumor tissue specimens for mismatch repair protein expression or microsatellite instability testing;
• No prior systemic drug therapy and/or radiotherapy for colorectal adenocarcinoma;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Normal major organ function, no severe blood, heart, lung, liver, kidney dysfunction, or immune deficiency diseases (see protocol for details);
• Voluntary participation in this study and signed informed consent form;
• Expected good compliance to complete the study treatment, follow-up for efficacy and adverse reactions according to the protocol requirements.

Exclusion Criteria:

• Pathology is other malignant tumors besides adenocarcinoma, such as squamous cell carcinoma, gastrointestinal stromal tumor, melanoma, etc.;
• Within 5 years prior to the first use of investigational drug, diagnosed with other malignant tumors, excluding effectively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ cervical cancer and/or breast cancer effectively removed;
• Any distant metastatic colorectal adenocarcinoma (according to AJCC 8th edition staging, determined as M1), including but not limited to distant lymph node metastasis, liver metastasis, lung metastasis, intraperitoneal dissemination, or malignant peritoneal effusion;
• Various severe underlying diseases and autoimmune diseases (see protocol for details);
• Unable to control recurrent bleeding or subjects who received blood transfusion within 2 weeks prior to the first use of investigational drug;
• Any other circumstances where the investigator believes it may increase the risk associated with participating in the study, the administration of the investigational drug, or affect the subject's ability to receive the investigational drug and the reliability of the study results.