A Phase III, Open Label, Randomised, 3-Arm, Multi-Centre Study of Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (SAMETA)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 148
- 试验地点
- 138
- 主要终点
- Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib
研究概览
简要总结
A clinical trial to compare the effectiveness of savolitinib plus durvalumab versus sunitinib in MET-driven (hepatocyte growth factor receptor), unresectable and locally advanced or metastatic PRCC (Papillary Renal Cell Carcinoma).
详细描述
This is a Phase III, randomised, open label, 3 arm, multi-centre, international study assessing the efficacy and safety of savolitinib plus durvalumab compared with sunitinib in participants with MET-driven (without co-occurring FH mutations), unresectable and locally advanced or metastatic PRCC, who have not received any prior systemic anti-cancer therapy in the metastatic setting. The study will also investigate the contribution of durvalumab to the savolitinib plus durvalumab combination.
Approximately 200 participants will be randomised in a 2:1:1 ratio to one of the following intervention groups: savolitinib (600mg, oral, once daily) plus durvalumab (1500mg IV Q4W), sunitinib (50mg, oral, once daily for 4 consecutive weeks, followed by a sunitinib-free interval of 2-weeks, Q6W), or durvalumab monotherapy (1500mg IV Q4W).
Participants will continue to receive study intervention until objective radiological PD per RECIST 1.1 is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.
Depending on the preferred subsequent therapy, participants randomised to the durvalumab monotherapy arm will be eligible to switch to receive savolitinib in combination with durvalumab at the time of objective radiological PD assessed by BICR per RECIST 1.1, without any intervening systemic anti-cancer therapy following discontinuation of durvalumab monotherapy.
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed unresectable and locally advanced or metastatic PRCC
- •PRCC must be centrally confirmed as MET-driven using a sponsor-designated central laboratory validated NGS assay
- •No prior systemic anti-cancer treatment in the metastatic setting; no prior exposure to MET inhibitors, Durvalumab or Sunitinib in any setting
- •Karnofsky Score >70
- •At least one lesion, not previously irradiated, that can be accurately measured at baseline
- •Adequate organ and bone marrow function
- •Life expectancy ≥12weeks at Day 1
排除标准
- •History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal LFTs
- •Spinal cord compression or brain metastases, unless asymptomatic and stable on treatment for at least 14 days prior to study intervention
- •Active or prior cardiac disease (within past 6 months) or clinically significant ECG abnormalities and/or factors/medications that may affect QT and/or QTc intervals
- •Active infection including HIV, TB, HBV and HCV
- •Active or prior documented autoimmune or inflammatory disorders
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention
研究组 & 干预措施
Arm A
savolitinib 600mg plus durvalumab 1500mg
干预措施: savolitinib (Drug)
Arm A
savolitinib 600mg plus durvalumab 1500mg
干预措施: durvalumab (Drug)
Arm B
sunitinib 50mg
干预措施: sunitinib (Drug)
Arm C
durvalumab 1500mg
干预措施: durvalumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to sunitinib
时间窗: Approximately 28 months post first subject randomized
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression.
次要结局
- Evaluation of the PK of savolitinib pre-dose(Approximately 28 months post first subject randomized)
- Evaluation of the PK of savolitinib post-dose(Approximately 28 months post first subject randomized)
- Progression-Free Survival (PFS) /savolitinib plus durvalumab relative to durvalumab monotherapy(Approximately 28 months post first subject randomized)
- Evaluation of the PK of durvalumab pre-dose(Approximately 28 months post first subject randomized)
- Evaluation of the PK of durvalumab / Cmax (maximum plasma concentration)(Approximately 28 months post first subject randomized)
- Overall Survival (OS) /savolitinib plus durvalumab relative to sunitinib(Approximately 28 months and approximately 42 months post first subject randomized)
- Objective Response Rate (ORR) / savolitinib plus durvalumab relative to sunitinib(Approximately 28 months post first subject randomized)
- Disease Control Rate (DCR) at 24 and 48 weeks /savolitinib plus durvalumab relative to sunitinib(Approximately 28 months post first subject randomized)
- Duration of Response (DoR) / savolitinib plus durvalumab relative to sunitinib(Approximately 28 months post first subject randomized)
- Time from randomisation to second progression or death (PFS2) /savolitinib plus durvalumab relative to sunitinib(Approximately 28 months and 42 months post first subject randomized)
- Assessment of patient-reported symptoms, functioning, and HRQoL /savolitinib plus durvalumab relative to sunitinib(Approximately 28 months post first subject randomized)
- Objective Response Rate (ORR) / savolitinib plus durvalumab relative to durvalumab monotherapy(Approximately 28 months post first subject randomized)
- Duration of Response (DoR) / savolitinib plus durvalumab relative to durvalumab monotherapy(Approximately 28 months post first subject randomized)