Envolimab Monotherapy or Envolimab + CAPEOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

Study Overview
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Brief Summary
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There exists substantial evidence suggesting that patients diagnosed with MSI-H/dMMR colorectal cancer can derive benefits from immunotherapy in the management of advanced colorectal cancer. In cases of locally advanced colorectal cancer exhibiting microsatellite instability (dMMR/MSI-H), patients exhibit low responsiveness to neoadjuvant chemotherapy, resulting in minimal rates of complete tumor remission and downstaging. Nevertheless, initial exploratory studies, characterized by modest sample sizes, reveal a favorable therapeutic effect of neoadjuvant immunotherapy in this particular patient population. Envality monoclonal antibody, the first PD-L1 antibody developed and manufactured in China, possesses noteworthy practical and societal value in the context of exploratory clinical research on neoadjuvant immunotherapy for locally advanced MSI-H/dMMR colorectal cancer patients. The objective of this study is to evaluate the safety and efficacy of Envality monoclonal antibody (PD-L1) as neoadjuvant therapy for locally advanced MSI-H/dMMR colorectal cancer through a prospective, multi-cohort phase II clinical trial. Additionally, this study aims to investigate the effectiveness and safety of Envality monoclonal antibody in combination with CAPEOX as a neoadjuvant treatment regimen for locally advanced pMMR colorectal cancer.

Official Title
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A Prospective, Single-center, Multi-cohort Study of Envolimab Monotherapy or Envolimab in Combination With CAPEOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer.

Conditions
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Colon Cancer, Neoadjuvant Therapy, Immunotherapy

Intervention / Treatment
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* Drug: Envafolimab
* Drug: CAPEOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological confirmed rectal cancer Clinical stage T3-4 or T any N1 With or without MRF positivity, with or without EMVI positivity R0 resection is estimated Age ranged from 18 to 70 Exclusion Criteria: Clinical stage T1-2 N0 Distance metastasis Multiple primary tumor Cachexy

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Envafolimab Group<br>Patients diagnosed with colon cancer, with T stage determined as 3-4 based on enhanced MR imaging, or with any T stage accompanied by imaging findings suggestive of lymph node metastasis, and excluding patients with distant metastasis, who are confirmed to have microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colon cancer, will be enrolled in Group A | Drug: Envafolimab<br>* Upon confirming eligibility based on inclusion criteria and obtaining signed informed consent, the patient will be administered Envafolimab at a dose of 300mg every 3 weeks (Q3W) for a total of 4 cycles, starting on Day 1.<br>|
| Active Comparator: Envafolimab+CAPEOX Group<br>Patients diagnosed with colon adenocarcinoma, with T stage determined as 3-4 based on enhanced MR imaging, or with any T stage accompanied by imaging findings suggestive of lymph node metastasis, and excluding patients with distant metastasis, who are confirmed to have microsatellite stable (MSS)/proficient mismatch repair (pMMR) colon cancer, will be enrolled in Group B. | Drug: Envafolimab<br>* Upon confirming eligibility based on inclusion criteria and obtaining signed informed consent, the patient will be administered Envafolimab at a dose of 300mg every 3 weeks (Q3W) for a total of 4 cycles, starting on Day 1.<br>Drug: CAPEOX<br>* The neoadjuvant treatment regimen will consist of Oxaliplatin at a dose of 130mg/m2, administered intravenously over a period of more than 2 hours on Day 1, every 3 weeks; and Capecitabine at a dose of 1000mg/m2, orally, twice daily from Day 1 to Day 14, every 3 weeks, for a total of 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pCR | rate of pathological complete remission | Time Frame: One week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | Disease free survival | 3 years |