Cadonilimab + FOLFOX Versus FOLFOX in the Neoadjuvant Treatment of pMMR/MSS Locally Advanced Colorectal Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the efficacy and safety of the combination of Cadonilimab and FOLFOX regimen compared to FOLFOX regimen alone in the neoadjuvant chemotherapy of pMMR/MSS locally advanced colorectal cancer. The main question aims to answer are: Question 1: Compare the pathological complete response rate between the combination of Cadonilimab and FOLFOX regimen and the FOLFOX alone. Question 2: Compare the survival outcomes and safety between the combination of Cadonilimab and FOLFOX regimen and the FOLFOX alone. Two groups of participants will receive different new adjuvant chemotherapy regimens, and their efficacy will be compared.

Detailed Description
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A prospective, randomized, open, single-center clinical study evaluating the efficacy (pathological response, survival outcomes) and safety of the combination of Cadonilimab and FOLFOX regimen compared to FOLFOX regimen in the treatment of locally advanced colorectal cancer with proficient mismatch-repair (pMMR) or microsatellite stable (MSS) protein expression.

Official Title
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Comparison of Cetuximab Combined With Chemotherapy Versus Chemotherapy Alone in the Neoadjuvant Treatment of Locally Advanced pMMR/MSS Colorectal Cancer: a Randomized, Open-label, Single-center Phase II Clinical Study

Conditions
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Locally Advanced Colorectal Carcinoma

Intervention / Treatment
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* Drug: Cadonilimab
* Drug: FOLFOX regimen


Participation Criteria
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Eligibility Criteria
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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, with mismatch repair protein expression result of pMMR, or microsatellite instability testing result of MSS; 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 adenocarcinoma but mismatch repair protein expression result is dMMR, or microsatellite instability testing result is MSI-H; or 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cadonilimab+FOLFOX group<br>Patients in this group will receive cetuximab combined with FOLFOX regimen, specifically: Cetuximab 6 mg/kg, intravenous infusion, D1; Oxaliplatin (85mg/m2), intravenous infusion, D1; Calcium folinate (400mg/m2), intravenous infusion, D1; 5-FU (400mg/m2), intravenous infusion, D1, then continuous intravenous infusion of 1200mg/(m2·d)×2d (total amount of 2400mg/m2, infusion for 46-48h) every two weeks; in the control group, qualified subjects will receive Oxaliplatin (85mg/m2), intravenous infusion, D1; Calcium folinate (400mg/m2), intravenous infusion, D1; 5-FU (400mg/m2), intravenous infusion, D1, then continuous intravenous infusion of 1200mg/(m2·d)×2d (total amount of 2400mg/m2, infusion for 46-48h) every two weeks. Imaging evaluation will be performed after 3 cycles of preoperative treatment. If the disease is resectable, surgery will be performed. If R0 resection is achieved, the preoperative regimen will continue for up to 9 cycles. | Drug: Cadonilimab<br>* PD-1/CTLA-4 bi-specific antibody<br>* Other names: 1;Drug: FOLFOX regimen<br>* FOLFOX chemotherapy<br>* Other names: 0;|
| Active Comparator: FOLFOX group<br>Patients in this group will undergo FOLFOX chemotherapy regimen, specifically: Oxaliplatin 85 mg/m2 dissolved in 500 ml of 5% glucose solution, intravenous drip, on Day 1, in combination with calcium folinate (400mg/m2), intravenous infusion, on Day 1, and 5-FU (400mg/m2), intravenous infusion, on Day 1, followed by continuous intravenous infusion of 1200mg/(m2·d) for 2 days (total dose of 2400mg/m2, infusion for 46-48 hours), once every 2 weeks. After 3 cycles of preoperative treatment, imaging evaluation will be performed. If the disease is resectable, surgery will be performed. If R0 resection is achieved, the preoperative treatment regimen will be continued after surgery, for a maximum of 9 cycles. | Drug: FOLFOX regimen<br>* FOLFOX chemotherapy<br>* Other names: 0;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR rate | pathological complete response rate | at time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | R0 resection rate | at time of surgical assessment (after 3 cycles), up to 12 months | 
| DFS | disease-free survival | up to 3 years after intervention | 
| 3 years DFS rate | 3 years DFS rate | 3 years | 
| OS | overall survival | at 1,2,3 years at follow-up time |