A Randomized Phase 2/3 Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma (HARMONi-GU1)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 7
- 主要终点
- Phase 3 Primary Outcome Measure
研究概览
简要总结
A Randomized, Open-Label, Multicenter, Phase 2/3 Clinical Study of Ivonescimab in Combination with Enfortumab Vedotin vs Pembrolizumab in Combination with Enfortumab Vedotin in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma (HARMONi-GU1)
详细描述
This Phase 2/3 study will be conducted in 2 parts. The first part is a Phase 2 randomized, open-label, 2 dose levels, parallel-arm study with the primary objective to evaluate safety and identify the recommended Phase 3 dose (RP3D) of ivonescimab in combination with EV. The second part is a randomized, open-label Phase 3 study with the primary objective to evaluate the efficacy and safety of ivonescimab (RP3D) plus EV versus pembrolizumab plus EV in patients with previously untreated LA/mUC.
For Phase 2 portion, patients will be randomized 1:1 to two arms consisting of 2 different dosages of ivonescimab.
- Arm A: Ivonescimab Dose 1 + EV
- Arm B: Ivonescimab Dose 2 + EV For Phase 3 portion, patients will be randomized 1:1 to the experimental arm (ivonescimab + EV) and the control arm (pembrolizumab + EV).
- Arm 1 (experimental): Ivonescimab RP3D + EV
- Arm 2 (SoC): Pembrolizumab 200 mg + EV
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years and older
- •Life expectancy ≥ 6 months
- •Histologically documented unresectable LA/mUC (transitional cell carcinoma) of the bladder, renal pelvis, ureter, or urethra with ≥50% urothelial carcinoma component
- •No prior systemic therapy for LA/mUC
- •At least one measurable non-cerebral lesion according to RECIST v1.1
- •Adequate organ function
排除标准
- •Locally advanced disease that is resectable or suitable for local therapy with curative intent.
- •Tumors containing any small cell or neuroendocrine differentiation
- •Ongoing sensory or motor neuropathy Grade 2 or higher.
- •Radiographic findings consistent with a high risk of bleeding
- •History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction, extensive bowel resection within 6 months prior to first dose.
研究组 & 干预措施
Phase 2: Arm A
Ivonescimab Dose 1 + EV
干预措施: enfortumab vedotin (EV) (Drug)
Phase 2: Arm B
Ivonescimab Dose 2 + EV
干预措施: enfortumab vedotin (EV) (Drug)
Phase 2: Arm A
Ivonescimab Dose 1 + EV
干预措施: Ivonescimab Dose 1 (Drug)
Phase 2: Arm B
Ivonescimab Dose 2 + EV
干预措施: Ivonescimab Dose 2 (Drug)
Phase 3: Arm 1
Ivonescimab RP3D (recommended Phase 3 dose) + EV
干预措施: Ivonescimab RP3D (Drug)
Phase 3: Arm 1
Ivonescimab RP3D (recommended Phase 3 dose) + EV
干预措施: enfortumab vedotin (EV) (Drug)
Phase 3: Arm 2
Pembrolizumab 200 mg + EV
干预措施: Pembrolizumab (Drug)
Phase 3: Arm 2
Pembrolizumab 200 mg + EV
干预措施: enfortumab vedotin (EV) (Drug)
结局指标
主要结局
Phase 3 Primary Outcome Measure
时间窗: From date of randomization until the end of study, assessed up to 4 years
Overall Survival (OS)
Phase 2 Primary Outcome Measure
时间窗: Through 90 days after the last study treatment
Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Phase 2 Primary Outcome Measure
时间窗: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years
Number of participants with clinical laboratory abnormalities
Phase 2 Primary Outcome measure
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Objective response rate (ORR)
Phase 2 Primary Outcome Measure
时间窗: From first dose until end of treatment, assessed up to 3 years
PK characteristics: ivonescimab serum concentration profiles
Phase 3 Primary Outcome Measure
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC)
次要结局
- Phase 2 Secondary Outcome Measure(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years)
- Phase 2 Secondary Outcome Measure(From date of randomization until the end of study, assessed up to 4 years)
- Phase 2 Secondary Outcome Measure(From time of initiation of first dose to 30 days after end of treatment.)
- Phase 3 Secondary Outcome Measure(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years)
- Phase 3 Secondary Outcome Measure(Through 90 days after the last study treatment)
- Phase 3 Secondary Outcome Measure(From first dose until approximately 30 days after the last study treatment, assessed up to 3 years)
- Phase 3 Secondary Outcome Measure(From first dose until end of treatment, assessed up to 3 years)
- Phase 3 Secondary Outcome Measure(From time of initiation of first dose to 30 days after end of treatment)