FORAGER-2: A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Vepugratinib Combined With Enfortumab Vedotin and Pembrolizumab in Adults With Untreated Locally Advanced or Metastatic Urothelial Carcinoma With an FGFR3 Genetic Alteration
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 478
- 主要终点
- Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab
研究概览
简要总结
The purpose of this study is to test a new medicine, vepugratinib, in comparison with placebo, to see if it is safe and can help people with a bladder cancer that is advanced or has spread.
Vepugratinib or placebo will be administered in combination with enfortumab vedotin and pembrolizumab.
Study participation could last up to approximately 6 years.
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)
盲法说明
There will be an open-label safety lead in.
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
- •Have histologically confirmed, unresectable locally advanced or metastatic urothelial cancer (mUC). Individuals with mixed histology other than small cell or neuroendocrine carcinoma are eligible if a urothelial component is present.
- •Have a qualifying fibroblast growth factor receptor 3 (FGFR3) genetic alteration determined via molecular testing from a tumor or blood sample obtained at or any time after diagnosis of advanced or metastatic urothelial cancer.
- •Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Have adequate laboratory parameters
排除标准
- •Have received prior systemic therapy for locally advanced or metastatic urothelial cancer (mUC).
- •Have any unresolved toxicities greater than Grade 1 Common Terminology Criteria for Adverse Events ([CTCAE] version 5.0) from prior neoadjuvant or adjuvant systemic therapy.
- •Have ongoing sensory or motor neuropathy of Grade 2 or higher
- •Have untreated or uncontrolled central nervous system (CNS) involvement or any history of leptomeningeal disease.
- •Current evidence corneal keratopathy or retinal disorder confirmed by ocular examination at screening.
研究组 & 干预措施
Vepugratinib + EV + Pembrolizumab (Safety Lead In)
Vepugratinib administered orally with EV + pembrolizumab administered IV
干预措施: Vepugratinib (Drug)
Vepugratinib + EV + Pembrolizumab (Safety Lead In)
Vepugratinib administered orally with EV + pembrolizumab administered IV
干预措施: EV (Drug)
Vepugratinib + EV + Pembrolizumab (Safety Lead In)
Vepugratinib administered orally with EV + pembrolizumab administered IV
干预措施: Pembrolizumab (Drug)
Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab
Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.
干预措施: EV (Drug)
Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab
Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.
干预措施: Pembrolizumab (Drug)
Placebo + EV + Pembrolizumab
Placebo administered orally, and EV + pembrolizumab administered by IV infusion.
干预措施: Pembrolizumab (Drug)
Placebo + EV + Pembrolizumab
Placebo administered orally, and EV + pembrolizumab administered by IV infusion.
干预措施: Placebo (Other)
Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab
Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.
干预措施: Vepugratinib (Drug)
Placebo + EV + Pembrolizumab
Placebo administered orally, and EV + pembrolizumab administered by IV infusion.
干预措施: EV (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab
时间窗: From baseline up to 90 months
Safety Lead-in: Overall Response Rate (ORR)
时间窗: From baseline up to 90 months
ORR by Investigator Assessment.
Progression-free Survival (PFS)
时间窗: Baseline to Study Completion (estimated as 6 years)
PFS by blinded independent committee review (BICR).
次要结局
- Safety Lead-in: Disease Control Rate (DCR)(From baseline up to the end of Cycle 2 (each Cycle is 21 days))
- Duration of Response (DoR)(Baseline to Study Completion (estimated as 6 years))
- Safety Lead-in: Time to Response (TTR)(From baseline up to 90 months)
- Overall Survival (OS)(Baseline to Study Completion (estimated as 6 years))
- Objective Response Rate (ORR) by BICR(Baseline to Study Completion (estimated as 6 years))
- Progression-free Survival (PFS)(Baseline to Study Completion (estimated as 6 years))
- Objective Response Rate (ORR)(Baseline to Study Completion (estimated as 6 years))
- Progression-free Survival 2 (PFS2)(Baseline to Study Completion (estimated as 6 years))
- Duration of Response (DOR)(Baseline to Study Completion (estimated as 6 years))
- Change from Baseline in Global Health Status/Quality of Life (QOL) and Physical Function Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline to Study Completion (estimated as 6 years))
- Plasma Concentrations of Vepugratinib(Cycle 1 Day 1 to Study completion (estimated as 90 months))