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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05371197
• Other study ID #: ENCC
• Status: Recruiting
• Phase: Phase 2
• Start date: May 5, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2022
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
China	the Third Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR) rates	Proportion of patients experiencing a pCR to perioperative PD-L1 antibody	1 year
Secondary	Major pathological response rates	The proportion of patients experiencing a major pathological response to perioperative PD-L1 antibody	1 year
Secondary	R0 resection rates	The proportion of patients experiencing a R0 resection after perioperative treatment with PD-L1 antibody	1 year
Secondary	Disease-free survival (DFS)	Defined as the time from randomization to relapse, metastasis or death from any cause	3 years
Secondary	Overall survival (OS)	Defined as the time from randomization to death from any cause	5 years
Secondary	Drug Safety	Assessed by evaluation of treatment-related adverse events	1 year
Secondary	Drug feasibility	Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose	1 year