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

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

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. Envafolimab 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 envafolimab 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 envafolimab monoclonal antibody in combination with CAPEOX as a neoadjuvant treatment regimen for locally advanced pMMR colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer; Neoadjuvant Therapy; Immunotherapy
• Intervention / Treatment: Drug: Envafolimab; Drug: CAPEOX

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenhai Lu, Prof; Phone Number: +862087343584; Email: luzhh@sysucc.org.cn
• Study Contact Backup: Name: Rongxin Zhang, Prof; Phone Number: +862087343584; Email: zhangrx@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Sub-Investigator: Rong-Xin Zhang, M.D.
      • Contact: Zhen-Hai Lu, Prof.; Phone Number: +86 20 87343584; Email: luzhh@sysucc.org.cn
      • Contact: Rong-Xin Zhang, Prof.; Phone Number: +86 20 87343456; Email: zhangrx@sysucc.org.cn
      • Principal Investigator: Zhen-Hai Lu, Prof.
      • Sub-Investigator: Zhi-Qiang Wang, M.D.
      • Sub-Investigator: Yuan Li, M.D.
      • Sub-Investigator: Fu-Long Wang, M.D
      • Sub-Investigator: Jian-Hong Peng, M.D.
      • Sub-Investigator: Jia-Li Chen, Bachelor
      • Sub-Investigator: Wei-Li Zhang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Envafolimab Group; 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; 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.
Active Comparator: Envafolimab+CAPEOX Group; 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; 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.; Drug: CAPEOX; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	O Overall survival	5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2022-FXY-256-Department of CRC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No