A PHASE 3, OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE ENFORTUMAB VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB IN ADULT PARTICIPANTS WITH MUSCLE-INVASIVE BLADDER CANCER WHO ARE INELIGIBLE FOR OR HAVE ELECTED NOT TO UNDERGO CYSTECTOMY
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 390
- 试验地点
- 14
- 主要终点
- Bladder-intact Event Free Survival (BI-EFS) by Blinded Independent Central Review (BICR)
研究概览
简要总结
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together as a bladder preservation approach to treat patients with muscle invasive bladder cancer. The study will compare these drugs to concurrent chemoradiotherapy that is usually used to treat this cancer (standard of care). The study will enroll patients with muscle-invasive bladder cancer (MIBC) who have cancer that has not spread outside the bladder.
详细描述
This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab versus standard of care concurrent chemoradiotherapy, in subjects with previously untreated muscle invasive bladder cancer.
Enfortumab vedotin may be administered for up to 9 cycles or a protocol defined reason for study discontinuation occurs, whichever is first. Pembrolizumab may be administered for a maximum of 17 cycles (3-week cycles) or a protocol-defined reason for study discontinuation occurs, whichever is first. Concurrent chemoradiotherapy may be administered for a maximum of 6.5 weeks.
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
盲法说明
Open-label
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
- •Has histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology staged cT2-T4aN0M0
- •Tissue comprising muscle-invasive urothelial cancer must be submitted for clinical staging at baseline
- •Eligible for and agree to receive chemoradiotherapy and one of the protocol-specified radiosensitizing chemotherapy regimens
- •Fit for systemic therapy and elect bladder preservation, including participants who are ineligible for or have elected not to undergo cystectomy
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
排除标准
- •Advanced or metastatic disease (N+, M1), non-urothelial carcinoma, diffuse or multifocal CIS, urothelial carcinoma or histological variant at any site outside the urinary bladder within previous 24 months prior to randomization except Ta/T1/CIS of the upper urinary tract including renal pelvis and ureter if the participant had undergone complete nephrectomy
- •Has received any prior systemic treatment, chemoradiation, and/or radiation for MIBC or NMIBC
- •Prior pelvic radiation for any reason
- •Inadequate bladder function
- •Other active malignancies within 3 years prior to randomization
- •Previously treated with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs)
- •Previously treated with a PD(L)-1 inhibitor, defined as a PD-1 inhibitor or PD-L1 inhibitor
- •Uncontrolled diabetes
- •Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted
- •Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection
- •Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
- •Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
- •Known genetic disorders associated with radiosensitivity (eg, ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi syndrome)
- •Active keratitis or corneal ulcerations
- •History of autoimmune disease that has required systemic treatment in the past 2 years
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Prior allogeneic stem cell or solid organ transplant
- •Received a live attenuated vaccine within 30 days prior to randomization
研究组 & 干预措施
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Mitomycin C (Drug)
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Cisplatin (Drug)
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Gemcitabine (Drug)
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Conventional Radiotherapy (Radiation)
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Hypofractionated Radiotherapy (Radiation)
Arm B
Concurrent Chemoradiotherapy (cCRT)
干预措施: Fluorouracil (Drug)
Arm A
Enfortumab vedotin + pembrolizumab (EV + P)
干预措施: Pembrolizumab (Drug)
Arm A
Enfortumab vedotin + pembrolizumab (EV + P)
干预措施: Enfortumab vedotin (Drug)
结局指标
主要结局
Bladder-intact Event Free Survival (BI-EFS) by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 45.5 months
BI-EFS is defined as the time from randomization to any of the following events: histologically confirmed persistent or residual MIBC post-treatment confirmed by BICR, histologically confirmed recurrent MIBC by BICR, disease progression by BICR, cystectomy, or death from any cause.
Overall Survival (OS)
时间窗: Up to approximately 60 months
Time from randomization to death due to any cause.
次要结局
- Time to Cystectomy(Up to approximately 60 months)
- Bladder-intact Event Free Survival (BI-EFS) by Investigator(Up to approximately 45.5 months)
- Complete clinical response (cCR) rate by Blinded Independent Central Review (BICR) and Investigator(Up to approximately 60 months)
- Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR) and Investigator(Up to approximately 60 months])
- Disease Free Survival (DFS) by Blinded Independent Central Review (BICR) and Investigator(Up to approximately 60 months)
- Cystectomy Free Survival (CFS)(Up to approximately 60 months)
- Number of Participants with Treatment Emergent Adverse Event (TEAE)(From start of study treatment up to 30 days after last dose of study drug (approximately up to 1.1 years))
- Number of Participants with Serious TEAEs(From start of treatment up to 90 days after the last dose of study treatment (approximately up to 1.3 years))