Back to results

Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer

Primary Purpose

Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Neoadjuvant therapy with PD-L1 inhibitor

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Willing and able to provide written informed consent.
Histological or cytological documentation of adenocarcinoma of the colon or rectum.
Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
Male or female subjects > 18 years < 70 of age.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]).
Non complicated primary tumor (obstruction, perforation, bleeding).
No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy.
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Exclusion Criteria:

Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
Heart failure grade III/IV (NYHA-classification).
Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
Subjects with known allergy to the study drugs or to any of its excipients.
Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
Breast- feeding or pregnant women
Lack of effective contraception.
Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
With any distant metastasis.

Sites / Locations

the Third Affiliated Hospital of Sun Yat-Sen UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PD-L1 inhibitor

Arm Description

Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab)

Outcomes

Primary Outcome Measures

Pathological complete response (pCR) rates

Proportion of patients experiencing a pCR to perioperative PD-L1 antibody

Secondary Outcome Measures

Major pathological response rates

The proportion of patients experiencing a major pathological response to perioperative PD-L1 antibody

R0 resection rates

The proportion of patients experiencing a R0 resection after perioperative treatment with PD-L1 antibody

Disease-free survival (DFS)

Defined as the time from randomization to relapse, metastasis or death from any cause

Overall survival (OS)

Defined as the time from randomization to death from any cause

Drug Safety

Assessed by evaluation of treatment-related adverse events

Drug feasibility

Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose

Full Information

NCT ID

NCT05371197

First Posted

November 29, 2021

Last Updated

May 10, 2022

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

1. Study Identification

Unique Protocol Identification Number

NCT05371197

Brief Title

Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer

Official Title

Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 5, 2022 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% of all CRC patients, and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in "N Engl J Med" showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response. In theory, anti-PD-L1 drugs should have fewer immune side-effects than anti-PD-1 drugs. However, there are no reports of anti-PD-L1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to investigate the efficacy and safety of anti-PD-L1 monoclonal antibody (Envafolimab) as neoadjuvant immuntherapy for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PD-L1 inhibitor

Arm Type

Experimental

Arm Description

Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab)

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant therapy with PD-L1 inhibitor

Intervention Description

Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab), 300mg, Q3W for 4 cycles

Primary Outcome Measure Information:

Title

Pathological complete response (pCR) rates

Description

Proportion of patients experiencing a pCR to perioperative PD-L1 antibody

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Major pathological response rates

Description

The proportion of patients experiencing a major pathological response to perioperative PD-L1 antibody

Time Frame

1 year

Title

R0 resection rates

Description

The proportion of patients experiencing a R0 resection after perioperative treatment with PD-L1 antibody

Time Frame

1 year

Title

Disease-free survival (DFS)

Description

Defined as the time from randomization to relapse, metastasis or death from any cause

Time Frame

3 years

Title

Overall survival (OS)

Description

Defined as the time from randomization to death from any cause

Time Frame

5 years

Title

Drug Safety

Description

Assessed by evaluation of treatment-related adverse events

Time Frame

1 year

Title

Drug feasibility

Description

Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing and able to provide written informed consent. Histological or cytological documentation of adenocarcinoma of the colon or rectum. Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR). Male or female subjects > 18 years < 70 of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]). Non complicated primary tumor (obstruction, perforation, bleeding). No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment. Exclusion Criteria: Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment. Heart failure grade III/IV (NYHA-classification). Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure. Subjects with known allergy to the study drugs or to any of its excipients. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study. Breast- feeding or pregnant women Lack of effective contraception. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways. With any distant metastasis.

Facility Information:

Facility Name

the Third Affiliated Hospital of Sun Yat-Sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510630

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiafeng Fang, M.D. & Ph.D.

Phone

+8613760660785

fangjf@mail.sysu.edu.cn

First Name & Middle Initial & Last Name & Degree

Jiafeng Fang, M.D. & Ph.D.

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer

We'll reach out to this number within 24 hrs