A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 50
- 主要终点
- Percentage of Participants Who Experienced At Least One Adverse Event (AE)
研究概览
简要总结
This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Substudy 04A will enroll participants with locally advanced or mUC whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors. The protocol infrastructure will enable the rolling assignment of investigational treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •The main inclusion and
排除标准
- •include but are not limited to the following:
- •Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
- •Arm A: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.
- •Arm A: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation.
- •Arm B: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression after treatment with an anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies; OR disease recurrence after treatment with an anti-PD-1/L1 mAb for MIUC administered as monotherapy or in combination with other checkpoint therapies >12 months after last dose of treatment with an anti-PD-1/L1 mAb.
- •Arm B: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion from a metastatic site or from a primary tumor that has become locally advanced and not previously irradiated.
- •Exclusion Criteria:
- •Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.
- •Active infection requiring systemic therapy.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- •Known history of human immunodeficiency virus (HIV).
- •Known history of hepatitis B or known hepatitis C virus infection.
研究组 & 干预措施
Arm A: Zilovertamab vedotin
Participants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met.
干预措施: Zilovertamab vedotin (Biological)
Arm B: Pembrolizumab and MK-3120
Participants will receive MK-3120 up to 5mg/kg administered on Day 1, Day 15 and Day 29 of each 6 week cycle until documented disease progression or any other discontinuation criterion is met and 400mg pembrolizumab on Day 1 of each 6 week cycle for up to 17 cycles (up to ~2 years).
干预措施: Pembrolizumab (Biological)
Arm B: Pembrolizumab and MK-3120
Participants will receive MK-3120 up to 5mg/kg administered on Day 1, Day 15 and Day 29 of each 6 week cycle until documented disease progression or any other discontinuation criterion is met and 400mg pembrolizumab on Day 1 of each 6 week cycle for up to 17 cycles (up to ~2 years).
干预措施: MK-3120 (Biological)
结局指标
主要结局
Percentage of Participants Who Experienced At Least One Adverse Event (AE)
时间窗: Up to approximately 5 years
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 5 years
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment
Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants who achieve a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Arm B: ORR as Assessed by Investigator
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants who achieve a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
次要结局
- Arm A: Duration of Response (DOR) as Assessed by BICR(Up to approximately 2 years)
- Arm B: DOR as Assessed by Investigator(Up to approximately 2 years)