Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin (BCG) Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 220
- 试验地点
- 245
- 主要终点
- Cohort 1, 2, and 3: Overall Complete Response (CR) Rate
研究概览
简要总结
The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in participants treated with TAR-200 alone with papillary disease only (Cohort 4).
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 diagnosis of persistent or recurrent high-risk non-muscle invasive bladder cancer (HR-NMIBC), (carcinoma in situ [CIS] or tumor in situ [Tis]), with or without papillary disease (T1, high-grade Ta) or papillary disease only (high-grade Ta or any T1 and absence of CIS), within 12 months of completion of the last dose of Bacillus Calmette-Guerin (BCG) therapy, in participants who have received adequate BCG. Mixed histology tumors are allowed if urothelial differentiation (transitional cell histology) is predominant. However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC)
- •All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS is acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the electronic case report form (eCRF) at screening cystoscopy. For participants with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for High-Grade Urothelial Carcinoma [HGUC])
- •Participants must be ineligible for or have elected not to undergo radical cystectomy
- •BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or at least 2 of 6 doses of a second induction course
- •Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
排除标准
- •Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV)
- •Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/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
- •Received a live virus vaccine within 30 days prior to the initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (for example, COVID-19) by local health authorities are allowed
- •Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive hepatitis B surface antigen (HBsAg) antibody and undetectable PCR are allowed)
- •Prior therapy with an anti-programmed-cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
研究组 & 干预措施
Cohort 1: TAR-200 and Cetrelimab
TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months).
干预措施: Cetrelimab (Biological)
Cohort 3: Cetrelimab
Participants with CIS, with or without papillary disease, will receive Cetrelimab which will be dosed Q3W through Week 78 (18 months).
干预措施: Cetrelimab (Biological)
Cohort 1: TAR-200 and Cetrelimab
TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months).
干预措施: TAR-200 (Drug)
Cohort 4: TAR-200 (Participants with Papillary Disease only)
TAR-200 is placed into the bladder through a urinary placement catheter in participants with papillary disease only, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).
干预措施: TAR-200 (Drug)
Cohort 2: TAR-200
TAR-200 is placed into the bladder through a urinary placement catheter in participants with CIS, with or without papillary disease, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).
干预措施: TAR-200 (Drug)
结局指标
主要结局
Cohort 1, 2, and 3: Overall Complete Response (CR) Rate
时间窗: Up to 5 years
Overall CR rate is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.
Cohort 4: Disease-free Survival (DFS)
时间窗: Up to 5 years
DFS will be measured as the time from the date of first dose of study treatment to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first.
Cohorts 1, 2, and 3: Overall Complete Response (CR) Rate
时间窗: From date of first dose up to clinical cut-off date 3rd July 2025 (up to 50 months)
Overall CR rate was defined as the percentage of participants who met at least one of the following: negative cystoscopy and negative (including atypical) centrally read urine cytology, or positive cystoscopy with biopsy-proven benign or low-grade non-muscle invasive bladder cancer (NMIBC) and negative (including atypical) centrally read cytology at any time point.
Cohort 4: Disease-free Survival (DFS)
时间窗: From date of first dose up to clinical cut-off date 3rd July 2025 (up to 50 months)
DFS was defined as the time from the date of first dose of study treatment to the time of one of the following events, whichever occurred first: (1) The first recurrence of high-risk disease (high-grade Ta, any T1 or CIS), (2) 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 occurred first, (3) Death due to any cause.
次要结局
- Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies(Predose, up to 3 years)
- Cohort 1, 2, and 3: Duration of Response (DOR)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Cohort 1, 2, and 4: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma(Up to Week 21)
- Number of Participants with Anti-cetrelimab Antibodies(Predose, up to 3 years)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores(Baseline, up to 3 years and 4 months)
- Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores(Baseline, up to 3 years and 4 months)
- Number of Participants with Adverse Events (AEs) by Severity Grades(Up to 5 years)
- Cohort 1and 3: Serum Concentration of Cetrelimab(At Weeks 0, 3, 12, 24, 48, 60, 84 (end of infusion) [EOI])
- Cohort 3: Serum Concentration of Cetrelimab(At Weeks 60 (EOI))
- Cohorts 1, 2, and 3: Number of Participants With at Least 12 Months Duration of Response(From onset of first CR up to clinical cut-off date 3rd July 2025 (up to 47.3 months))
- Overall Survival (OS)(From Week 0 up to 6 years 7 months)
- Cohorts 1, 2, and 4: Plasma Concentrations of Gemcitabine and 2',2' Difluorodeoxyuridine (dFdU) (Metabolite)(Predose at Week 0 and at any time between Days 2-7 during Weeks 3, 6, 9, 15, 18, and 21 postdose)
- Cohorts 1 and 2: Maximum Observed Urine Concentration (Cmax) of Gemcitabine and dFdU (Metabolite)(At Week 0)
- Cohort 4: Urine Concentration of Gemcitabine and dFdU (Metabolite)(At Weeks 3, 6, 9, 15, 18, and 21)
- Cohorts 1 and 3: Number of Participants With Anti-cetrelimab Antibodies(From date of first dose up to clinical cut-off date 3rd July 2025 (54 months))
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores(From Week 0 up to 6 years 7 months)
- Change From Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores(From Week 0 up to 6 years 7 months)
- Time to Symptom Deterioration as Assessed by European Organisation for Research and Treatment of Cancer Qualityof-life Questionnaire (EORTC QLQ) -C30 Scores(From Week 0 up to 6 years 7 months)
- Time to Symptom Deterioration as Assessed by EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores(From Week 0 up to 6 years 7 months)
- Number of Participants With Adverse Events (AEs) by Severity Grades(From Week 0 up to 6 years 7 months)
- Number of Participants With Clinical Laboratory Abnormalities by Severity Grades(From Week 0 up to 6 years 7 months)