Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PD-L1 inhibitor Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab) |
Drug: Neoadjuvant therapy with PD-L1 inhibitor
Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab), 300mg, Q3W for 4 cycles
|
Outcome Measures
Primary Outcome Measures
- Pathological complete response (pCR) rates [1 year]
Proportion of patients experiencing a pCR to perioperative PD-L1 antibody
Secondary Outcome Measures
- Major pathological response rates [1 year]
The proportion of patients experiencing a major pathological response to perioperative PD-L1 antibody
- R0 resection rates [1 year]
The proportion of patients experiencing a R0 resection after perioperative treatment with PD-L1 antibody
- Disease-free survival (DFS) [3 years]
Defined as the time from randomization to relapse, metastasis or death from any cause
- Overall survival (OS) [5 years]
Defined as the time from randomization to death from any cause
- Drug Safety [1 year]
Assessed by evaluation of treatment-related adverse events
- Drug feasibility [1 year]
Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willing and able to provide written informed consent.
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Histological or cytological documentation of adenocarcinoma of the colon or rectum.
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Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
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Male or female subjects > 18 years < 70 of age.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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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]).
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Non complicated primary tumor (obstruction, perforation, bleeding).
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No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy.
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Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.
Exclusion Criteria:
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Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
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Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
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Heart failure grade III/IV (NYHA-classification).
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Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
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Subjects with known allergy to the study drugs or to any of its excipients.
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Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
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Breast- feeding or pregnant women
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Lack of effective contraception.
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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.
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With any distant metastasis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | the Third Affiliated Hospital of Sun Yat-Sen University | Guangzhou | Guangdong | China | 510630 |
Sponsors and Collaborators
- Third Affiliated Hospital, Sun Yat-Sen University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENCC