Short-course PD-1 Blockade As Adjuvant Treatment for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer.
The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival.
As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.
详细描述
This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer.
Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer.
Secondary objectives:
- To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care
- To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs).
OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •dMMR and/or MSI-H colorectal carcinoma that undergo surgical resection
- •Pathologically confirmed as stage II (T3-4,N0), with at least one of the following risk factors:
- •T4 (T4a and T4b)
- •Vascular invasion (VI)
- •Perineural invasion (PNI)
- •Poor differentiation (including mucinous and signet-ring carcinoma)
- •Obstruction and/or perforation before surgery
- •Perioperative CT/MR/PET-CT find no signs of metastases
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
- •Aged 18-80
- •No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current cancer
- •Adequate organ function
排除标准
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Positive surgical margin (R1/R2 resection)
- •Presence of post-operative complications that may preclude treatment
- •Active infection requiring systemic therapy
- •Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%.
研究组 & 干预措施
Tislelizumab Arm
Two cycles of Tislelizumab 200mg intravenously, on day 1 and day 22, with or without adjuvant chemotherapy
干预措施: Tislelizumab (Drug)
Tislelizumab Arm
Two cycles of Tislelizumab 200mg intravenously, on day 1 and day 22, with or without adjuvant chemotherapy
干预措施: Adjuvant chemotherapy (Drug)
Control Arm
Receiving standard of Care (either with adjuvant chemotherapy or surveillance alone).
干预措施: Adjuvant chemotherapy (Drug)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: 3 years
DFS (tumor-specific) is defined as time from randomization to tumor relapse or tumor-related death. DFS will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. If zero DFS events are observed in a certain stratum at an interim analysis and unstratified log-rank is used, all subsequent analyses for DFS will use unstratified log-rank test.
次要结局
- Overall survival (OS)(5 years)
- Incidence of adverse events(up to 30 days after last treatment)
研究者
Pei-Rong Ding
M.D.
Sun Yat-sen University