A Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 325
- 试验地点
- 136
- 主要终点
- Cohort A (Arm 1 and 2): Complete response rate
研究概览
简要总结
This is a Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk Non-Muscle-Invasive Bladder Cancer.
详细描述
In Cohort A, up to 125 participants will be enrolled with pathologically confirmed, high-risk high-grade non-muscle invasive bladder cancer (NMIBC) NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which is naïve to Bacillus Calmette-Guerin (BCG) treatment. Participants with CIS with or without concomitant Ta/T1 NMIBC at baseline will be randomized 1:1 to receive cretostimogene via the current (Arm 1) or an alternative instillation procedure (Arm 2). Participants with papillary-only high-risk NMIBC (i.e., HG Ta/T1 without CIS) at baseline (Arm 3) will receive cretostimogene via the alternative instillation procedure.
In Cohort B, up to 150 participants will be enrolled with pathologically confirmed, high-risk high-grade NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which has previously been exposed to BCG treatment. Participants with CIS-containing pathology at baseline will be recruited into Arm 1 and participants with papillary-only pathology at baseline will be recruited into Arm 2. Both Cohort B Arms 1 and 2 will receive cretostimogene via the alternative instillation procedure.
In Cohort CX, up to 50 participants will be enrolled with pathologically confirmed, high-risk high-grade NMIBC (i.e., CIS with or without concomitant Ta or T1 disease OR HG Ta/T1 disease without CIS) which has previously been exposed to or is unresponsive to BCG treatment. Participants will be randomized 1:1 to receive cretostimogene and gemcitabine either concurrently or sequentially.
In all cohorts, study treatment will be administered as a weekly induction course for the first 6 weeks with a reinduction course administered to patients who have CIS and/or high-grade Ta disease at the 3-month evaluation. Following induction, if no high-grade disease is detected, maintenance treatment will begin. This consists of a cycle of three weekly treatments every three months during the first year, and every six months during the second year, with an optional extension to the third year following the same six-month schedule.
Disease status will be assessed using urine cytology, complete bladder visualization (e.g., cystoscopy), upper tract assessment and directed resection/biopsy (if indicated) every 3 months for the first 2 years and then every 6 months for a further 2 years or until disease recurrence.
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
- •Cohort A Key Inclusion Criteria:
- •Pathologically confirmed BCG-naïve high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- •All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- •Acceptable baseline organ function.
- •Cohort B Key Inclusion Criteria:
- •Pathologically confirmed BCG-exposed high-risk high-grade NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- •All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- •Acceptable baseline organ function.
- •Cohort CX Inclusion Criteria
- •Pathologically confirmed high-risk high-grade BCG-unresponsive or BCG-exposed NMIBC (i.e., CIS with or without Ta/T1 disease or high-grade Ta/T1 papillary-only disease without CIS) within 90 days of treatment allocation.
- •All visible disease must be resected, and all CIS resected or fulgurated, as feasible within 90 days prior to treatment allocation.
- •Acceptable baseline organ function.
排除标准
- •(Both Cohorts):
- •Current or past history of muscle-invasive, locally advanced or metastatic bladder cancer.
- •High-grade urothelial carcinoma in the upper urinary tract or prostatic urethra within 24 months or T2 in upper tract within 48 months or any history of locally advanced/ nodal or metastatic disease in the upper urinary tract.
- •Significant immunodeficiency.
- •Pregnant or breastfeeding.
- •Cohort CX Only: serial intravesical gemcitabine within 24 months
研究组 & 干预措施
Experimental: Cohort CX, Arm 1
At all treatment visits cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method followed by gemcitabine instilled intravesically
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort A, Arm 3
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort B, Arm 1
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort B, Arm 2
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort CX, Arm 2
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method for two consecutive weeks, followed by gemcitabine administered intravesically in the third week on a cyclic 2:1 visit schedule basis
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort A, Arm 1
Cretostimogene (1 x 1012 vp) will be administered intravesically via the current instillation method
干预措施: Cretostimogene Grenadenorepvec (Drug)
Experimental: Cohort A, Arm 2
Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.
干预措施: Cretostimogene Grenadenorepvec (Drug)
结局指标
主要结局
Cohort A (Arm 1 and 2): Complete response rate
时间窗: At 11 and 24 weeks
Determine the complete response rate at any time following treatment with cretostimogene in participants with BCG-naïve CIS with or without concomitant high-grade Ta or T1 disease at baseline
Cohort A (Arm 3): High- Grade Event-Free Survival
时间窗: 48 months
Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-naïve HG Ta/T1 disease without concomitant CIS at baseline.
Cohort B (Arm 1): Complete response rate
时间窗: At 11 and 24 weeks
Determine the complete response rate at any time following treatment with cretostimogene in participants with BCG-exposed CIS with or without concomitant high-grade Ta or T1 disease at baseline.
Cohort B (Arm 2): High-Grade Event-Free Survival
时间窗: 48 months
Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-exposed high-grade Ta/T1 papillary disease without CIS at baseline.
Cohort CX (Arms 1 and 2): High-Grade Event-Free Survival
时间窗: 48 months
Determine the High-Grade Event-Free Survival following treatment with cretostimogene in participants with BCG-exposed or BCG-unresponsive high-grade NMIBC.
Cohort CX (Arms 1 and 2): Safety
时间窗: 48 months
Determine the safety of concurrent cretostimogene and gemcitabine and sequential cretostimogene and gemcitabine.
次要结局
- Cohort A (Arms 1 and 2): Evaluate cretostimogene instillation methods(At 11 and 24 weeks)
- Cohort A (Arm 3): High-Grade Event-Free Survival at 12 months(At 12 months)
- Cohort A (Arms 1 and 2) and Cohort B (Arm 1) Duration of response(48 months)
- Cohort B (Arm 2) High-Grade Event-Free Survival at 12 months(At 12 months)
- Cohort CX (Arm 1 and 2) Complete response rate(At 11 and 24 weeks)