A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 163
- 试验地点
- 189
- 主要终点
- Pathologic Complete Response (pCR) Rate
研究概览
简要总结
The purpose of this study is to evaluate the anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.
详细描述
Bladder cancer is the tenth most common malignancy worldwide. Approximately 25 percent (%) of all new bladder cancer participants present with muscle invasive bladder cancer (MIBC) at the time of diagnosis, and roughly 50% will ultimately develop distant metastases. The TAR-200/ gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets 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 standard of care in MIBC includes radical cystectomy (RC) with urinary diversion and is considered the preferred treatment option for participants who are considered surgical candidates. Study consists of a Screening phase, Treatment phase and follow-up phase. The total duration of study will be up to 2 years and 6 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during this 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 proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible
- •Participants with no residual tumor, or intravesical tumor size of less than or equal to (<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is >3 cm after debulking TURBT
- •Deemed eligible for and willing to undergo RC by the operating urologist
- •Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
- •Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results
- •All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization
排除标准
- •Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment
- •Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography [CT] or magnetic resonance imaging [MRI]) within 42 days prior to randomization
- •Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200
- •Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time
- •Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment
- •Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing
研究组 & 干预措施
Cohort 1: TAR-200 + Cetrelimab
Participants will receive TAR-200 in combination with cetrelimab.
干预措施: TAR-200 (Drug)
Cohort 1: TAR-200 + Cetrelimab
Participants will receive TAR-200 in combination with cetrelimab.
干预措施: Cetrelimab (Biological)
Cohort 2: Cetrelimab
Participants will receive cetrelimab.
干预措施: Cetrelimab (Biological)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate
时间窗: At Week 12
pCR was defined as percentage of participants who achieved complete pathologic response. Complete pathologic response is defined as ypT0N0 (no evidence of disease) as assessed by pathologic evaluation on radical cystectomy (RC) specimen. pCR was determined by central pathologic review.
次要结局
- Number of Participants With Treatment Emergent Adverse Event According to Common Terminology Criteria for Adverse Event (CTCAE) Version 5 Grades(Cycle Day 1 up to Week 124)
- Number of Participants With Worst Post-baseline Laboratory Values Based on Common Terminology Criteria for Adverse Events (CTCAE)(Cycle Day 1 up to Week 124)
- Recurrence-Free Survival (RFS)(Cycle Day 1 up to Week 124)