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

NCT05371197 | Unknown Phase 2

• 1 other identifier: ENCC
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rates

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

  1 year

Secondary Outcomes (6)

• Major pathological response rates

  1 year

• R0 resection rates

  1 year

• Disease-free survival (DFS)

  3 years

• Overall survival (OS)

  5 years

• Drug Safety

  1 year

Study Arms (1)

PD-L1 inhibitor

EXPERIMENTAL

Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab)

Drug: Neoadjuvant therapy with PD-L1 inhibitor

Interventions

Neoadjuvant therapy with PD-L1 inhibitor DRUG

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

PD-L1 inhibitor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

the Third Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510630, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

Neoadjuvant Therapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-president of Third Affiliated Hospital, Sun Yat-Sen University

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: May 12, 2022
• Study Start: May 5, 2022
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: May 12, 2022

Record last verified: 2022-05

Locations

CN (1)