Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rates
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
PD-L1 inhibitor
Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab)
干预措施: Neoadjuvant therapy with PD-L1 inhibitor (Drug)
结局指标
主要结局
Pathological complete response (pCR) rates
时间窗: 1 year
Proportion of patients experiencing a pCR to perioperative PD-L1 antibody
次要结局
- R0 resection rates(1 year)
- Disease-free survival (DFS)(3 years)
- Overall survival (OS)(5 years)
- Major pathological response rates(1 year)
- Drug Safety(1 year)
- Drug feasibility(1 year)
研究者
Hongbo Wei
Vice-president of Third Affiliated Hospital, Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University