A Phase 3, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Either Cisplatin or Carboplatin +Gemcitabine + Tislelizumab Compared With Either Cisplatin or Carboplatin + Gemcitabine + Placebo as First-line Treatment for Patients With Locally Advanced or Metastatic Urothelial Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 420
- 试验地点
- 79
- 主要终点
- Overall survival (OS) in the Intent to Treat (ITT) set
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to compare the efficacy and safety of tislelizumab + either cisplatin or carboplatin + gemcitabine versus placebo+ either cisplatin or carboplatin + gemcitabine in approximately 420 participants with locally advanced or metastatic urothelial carcinoma who have not received prior systemic therapy.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 to 75 years on the day of signing the Informed Consent Form (ICF)
- •Histologically confirmed, inoperable, locally advanced, or metastatic urothelial cancer (UC)
- •Must be eligible to receive cisplatin or carboplatin in the investigator's judgment
- •Have had no prior systemic chemotherapy for locally advanced or metastatic UC
- •Must be able to provide fresh or archival tumor tissues with an associated pathological report.
- •Must have evaluable disease (either measurable or non-measurable) as defined per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Adequate organ function before randomization:
排除标准
- •Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- •Any approved anticancer therapy within 28 days before randomization.
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •Participants with uncontrolled hypercalcemia
- •Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
- •History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases
- •A known history of HIV infection.
- •Prior allogeneic stem cell transplantation or organ transplantation.
- •History of severe hypersensitivity reactions to other monoclonal antibodies. 10．History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Placebo in combination with chemotherapy
Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Placebo (Drug)
Tislelizumab in combination with chemotherapy
Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Gemcitabine Hydrochloride (Drug)
Placebo in combination with chemotherapy
Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Cisplatin (Drug)
Placebo in combination with chemotherapy
Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Carboplatin (Drug)
Tislelizumab in combination with chemotherapy
Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Carboplatin (Drug)
Tislelizumab in combination with chemotherapy
Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Tislelizumab (Drug)
Tislelizumab in combination with chemotherapy
Tislelizumab: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Cisplatin (Drug)
Placebo in combination with chemotherapy
Placebo: Day 1 of each 21-day cycle, to be administered until Progressive Disease or intolerable toxicity Cisplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Carboplatin: Day 1 or Day 2 of each 21-day cycle, to be administered up to 6 cycles Gemcitabine: Days 1 and 8 of each 21-day cycle, to be administered up to 6 cycles
干预措施: Gemcitabine Hydrochloride (Drug)
结局指标
主要结局
Overall survival (OS) in the Intent to Treat (ITT) set
时间窗: From first randomization up to 3.5 years, approximately
次要结局
- Overall response rate (ORR) per RECIST v1.1 in ITT(From first randomization up to 3.5 years, approximately)
- Duration of response (DOR)(From first randomization up to 3.5 years, approximately)
- Progression-free survival (PFS)(From first randomization up to 3.5 years, approximately)
- Overall survival rate at 1 and 2 years for each treatment arm(From first randomization up to 3.5 years, approximately)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30)(From first randomization up to 3.5 years, approximately)
- Incidence and severity of treatment-emergent adverse events (AEs)(From first randomization up to 3.5years, approximately)
- Overall response rate (ORR) per RECIST v1.1 in ITT(From first randomization up to 3.5 years, approximately)
- Duration of response (DOR)(From first randomization up to 3.5 years, approximately)
- Progression-free survival (PFS)(From first randomization up to 3.5 years, approximately)
- Overall survival rate at 1 and 2 years for each treatment arm(From first randomization up to 3.5 years, approximately)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life-Core 30(EORTC QLQC30)(From first randomization up to 3.5 years, approximately)
- Incidence and severity of treatment-emergent adverse events (AEs)(From first randomization up to 3.5years, approximately)
- Change from baseline in European Quality of Life 5-Dimension, 5-Level version (EQ-5D-5L)(From first randomization up to 3.5 years, approximately)