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

NCT ID: NCT05371197

Last Updated: 2022-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-05
• Study Completion Date: 2024-12-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PD-L1 inhibitor

Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab)

Group Type: EXPERIMENTAL

Neoadjuvant therapy with PD-L1 inhibitor

Intervention Type: DRUG

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

Interventions

Neoadjuvant therapy with PD-L1 inhibitor

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Willing and able to provide written informed consent.

2. Histological or cytological documentation of adenocarcinoma of the colon or rectum.

3. Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).

4. Male or female subjects > 18 years < 70 of age.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. 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]).

7. Non complicated primary tumor (obstruction, perforation, bleeding).

8. No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy.

9. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Exclusion Criteria

1. Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.

2. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.

3. Heart failure grade III/IV (NYHA-classification).

4. Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.

5. Subjects with known allergy to the study drugs or to any of its excipients.

6. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.

7. Breast- feeding or pregnant women

8. Lack of effective contraception.

9. 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.

10. With any distant metastasis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Hongbo Wei

Vice-president of Third Affiliated Hospital, Sun Yat-Sen University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

the Third Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

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

Role: primary

fangjf@mail.sysu.edu.cn

+8613760660785

Other Identifiers

ENCC

Identifier Type: -

Identifier Source: org_study_id