Chemoradiation Versus Chemotherapy in Combination with Tislelizumab As First Line Treatment for Advanced Esophageal Squamous Cell Carcinoma with Low PD-L1 Expression (RENMIN-236): Multicentre, Randomised, Phase 3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 155
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study is a multicentre, randomised, parallel-controlled, open-label, 3 phase clinical trial. The subjects were untreated, unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma with low PD-L1 expression. Patients were randomly assigned to receive chemoradiation or chemotherapy in combination with Tislelizumab at a ratio of 1: 1. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We hypothesized that in advanced esophageal squamous cell carcinoma patients with low PD-L1 expression, chemoradiation versus chemotherapy in combination with Tislelizumab will significantly improve PFS.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically confirmed squamous cell carcinoma of esophagus (per AJCC 8th edition).
- •Subjects must have unresectable advanced, recurrent or metastatic ESCC.
- •Subjects must not be amenable to curative approaches such as definitive chemoradiation and/or surgery.
- •PD-L1 expression (CPS) is less than
- •No prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease.
- •ECOG Performance Status of 0 or
- •Subjects must have at least one measurable lesion by CT or MRI per RECIST 1.1 criteria; radiographic tumor assessment must be performed within 28 days prior to randomization.
- •Subjects must have adequate organ and bone marrow function.
排除标准
- •Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment.
- •Active known or suspected autoimmune disease.
- •Any serious or uncontrolled medical disorder or active infection.
- •Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus.
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
研究组 & 干预措施
Chemotherapy + Tislelizumab
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Cisplatin (Drug)
Chemoradiation + Tislelizumab
Intensity-modulated radiotherapy (IMRT):
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
During concurrent radiation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW
During consolidation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Intensity-modulated radiotherapy (IMRT) (Radiation)
Chemoradiation + Tislelizumab
Intensity-modulated radiotherapy (IMRT):
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
During concurrent radiation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW
During consolidation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Tislelizumab (Drug)
Chemoradiation + Tislelizumab
Intensity-modulated radiotherapy (IMRT):
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
During concurrent radiation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW
During consolidation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Cisplatin (Drug)
Chemoradiation + Tislelizumab
Intensity-modulated radiotherapy (IMRT):
Esophageal primary tumor: 39.6Gy/2.2Gy Bone metastasis: 30Gy/3Gy Lung, liver, brain metastases, metastatic lymph nodes: 45Gy/3Gy
During concurrent radiation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 75 mg/m² IV QW Drug: Cisplatin 25 mg/m² IV QW
During consolidation therapy:
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Nab paclitaxel (Drug)
Chemotherapy + Tislelizumab
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Tislelizumab (Drug)
Chemotherapy + Tislelizumab
Drug: Tislelizumab 200 mg IV Q3W Drug: Nab Paclitaxel 220 mg/m² IV Q3W Drug: Cisplatin 75 mg/m² IV Q3W
干预措施: Nab paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Approximately 40 months from date of the first participant randomization
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first
次要结局
- Overall Survival (OS)(Approximately 40 months from date of the first participant randomization)
- Objective Response Rate (ORR)(Approximately 40 months from date of the first participant randomization)
- Duration of Response (DOR)(Approximately 40 months from date of the first participant randomization)
- Number of participants experiencing Adverse Events (AEs)(Approximately 40 months from date of the first participant randomization)
研究者
Yongshun Chen
Professor
Renmin Hospital of Wuhan University