A Phase 3, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,135
- 试验地点
- 241
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
The purpose of this study is to compare event-free survival (EFS) in participants with Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive bladder cancer (HR-NMIBC), including high-grade papillary Ta, any T1, or carcinoma in situ (CIS), between TAR-200 plus cetrelimab (Group A) and TAR-200 alone (Group C) versus intravesical BCG (Group B).
详细描述
Bladder cancer is the tenth most common malignancy worldwide. About 75 percent (%) of bladder cancers are non-muscle invasive at diagnosis with approximately 25% of NMIBC patients have HR, NMIBC. The TAR-200/gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine and osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The mainstay of treatment for HR-NMIBC is transurethral resection of bladder tumor, followed by intravesical treatment with BCG. In this study metronomic dosing of intravesical gemcitabine, delivered via TAR-200, alone or in combination with cetrelimab will be evaluated and compared against intravesical BCG. The study consists of a Screening phase, Treatment phase, and Follow-up phase. The total duration of the study will be up to 5 years and 2 months. Efficacy, Safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during the study.
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
- •Histologically confirmed initial diagnosis by local pathology (within 90 days of the most recent signed informed consent) of high grade non-muscle invasive bladder cancer (HR-NMIBC) (high-grade Ta, any T1 or carcinoma in-situ [CIS]), in participants who are Bacillus Calmette Guérin (BCG)-naïve
- •BCG-naïve (participants who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before date of randomization are eligible)
- •All visible papillary disease must be fully resected (absent) prior to date of randomization and documented at baseline cystoscopy. Local urine cytology at screening must be negative or atypical (for high-grade urothelial carcinoma [HGUC]) for patients with papillary only disease (without CIS)
- •Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
- •All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to date of randomization
- •Participants must be willing to undergo all study procedures
排除标准
- •Presence or history of histologically confirmed, muscle invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, greater than and equal to [>=] T2)
- •Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (that is, urethra, ureter, or renal pelvis). Ta/any T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization
- •Presence of any bladder or urethral anatomic feature (example, urethral stricture) that, in the opinion of the investigator, may prevent the safe insertion, indwelling use, removal of TAR-200 or administration of intravesical BCG. Participants with tumors involving the prostatic urethra in men will be excluded
- •A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 milliliters (mL)
- •Indwelling catheters are not permitted; however, intermittent catheterization is acceptable
研究组 & 干预措施
Treatment Group B: Bacillus Calmette-Guerin (BCG) Vesiculture
Participants will receive intravesical BCG once every week for 6 weeks (induction) and then followed by once every week for 3 weeks starting at Weeks 12, 24, 48, 72, and 96 (maintenance).
干预措施: BCG Vesiculture (Biological)
Treatment Group C: TAR-200 Alone
Participants will receive intravesical TAR-200 alone once Q3W.
干预措施: TAR-200 (Drug)
Treatment Group A: TAR-200 + Cetrelimab
Participants will receive intravesical TAR-200 once every 3 weeks (Q3W) and cetrelimab.
干预措施: Cetrelimab (Biological)
Treatment Group A: TAR-200 + Cetrelimab
Participants will receive intravesical TAR-200 once every 3 weeks (Q3W) and cetrelimab.
干预措施: TAR-200 (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: Up to 5 years 2 months
EFS is defined as the time from randomization to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first. For participants with carcinoma In-situ (CIS), persistent disease at 6 months (Week 24) is also considered an EFS event. Progression is defined as: an increase of stage from Ta to T1 or from CIS to T1 or progression to muscle invasive bladder cancer (MIBC) (T greater than or equal to \[\>=\] 2) or to lymph node (N+) or to distant disease (M+), whichever occurs first.
次要结局
- Overall Complete Response (CR) Rate(Up to 5 years 2 months)
- Duration of CR(Up to 5 years 2 months)
- Recurrence-Free Survival (RFS)(Up to 5 years 2 months)
- Time to Progression (TTP)(Up to 5 years 2 months)
- Overall Survival (OS)(Up to 5 years 2 months)
- Cancer Specific Survival (CSS)(Up to 5 years 2 months)
- Number of Participants with Adverse Events (AEs) by Grades According to Common Terminology Criteria for Adverse Events (CTCAE)(Up to 5 years 2 months)
- Number of Participants with Adverse Events (AEs)(Up to 5 years 2 months)
- Number of Participants with Change from Baseline in Laboratory Abnormalities(Up to 5 years 2 months)
- Number of Participants with Change from Baseline in Vital Signs Abnormalities(Up to 5 years 2 months)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of life Questionnaire - Non-muscle Invasive Bladder Cancer EORTC QLQ- NMIBC 24(Up to 5 years 2 months)
- Time to Symptom Deterioration as Assessed by EORTC-QLQ-NMIBC 24 Scores(Up to 5 years 2 months)