A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 135
- 主要终点
- Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.
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
盲法说明
The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
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
- •Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
- •Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12 months following completion of therapy.
- •Measurable disease based on RECIST v1.
- •Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function per protocol-defined criteria.
排除标准
- •Urothelial carcinoma that is suitable for local therapy with curative intent.
- •History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging.
- •Active autoimmune disease that has required systemic treatment in past 2 years.
- •Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
- •Known history of or is positive for active hepatitis B (HBsAg reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
- •Use of protocol-defined prior/concomitant therapy.
研究组 & 干预措施
Pembrolizumab 200 mg + Epacadostat 100 mg BID
Pembrolizumab + epacadostat
干预措施: Pembrolizumab (Drug)
Pembrolizumab 200 mg + Epacadostat 100 mg BID
Pembrolizumab + epacadostat
干预措施: Epacadostat (Drug)
Pembrolizumab 200 mg + placebo BID
Pembrolizumab + placebo
干预措施: Pembrolizumab (Drug)
Pembrolizumab 200 mg + placebo BID
Pembrolizumab + placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
时间窗: up to 9 weeks +14 days
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
次要结局
- Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE(Up to 8 months)
- Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)(Up to 8 months)