A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 808
- 试验地点
- 302
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy [gemcitabine plus cisplatin] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).
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
- •Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
- •Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
- •Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
- •Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Have adequate organ function.
排除标准
- •Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
- •Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
- •Has ≥N2 disease or metastatic disease (M1) as identified by imaging
- •Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
- •Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
- •Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
- •Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
- •Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
- •Has a known psychiatric or substance abuse disorder
- •Has had an allogenic tissue/solid organ transplant
- •Has ongoing sensory or motor neuropathy Grade 2 or higher
- •Has active keratitis (superficial punctate keratitis) or corneal ulcerations
- •Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms
研究组 & 干预措施
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
干预措施: Enfortumab vedotin (EV) (Biological)
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
干预措施: RC + PLND (Procedure)
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
干预措施: Pembrolizumab (Biological)
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
干预措施: RC + PLND (Procedure)
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
干预措施: Cisplatin (Drug)
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: Up to ~68 months
EFS is defined as the time from randomization to the first occurrence of following events: radiographic disease progression precluding RC + PLND, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause.
次要结局
- Pathologic Downstaging (pDS) Rate(Up to ~47 months)
- Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale(Baseline, Up to ~68 months)
- Disease Free Survival (DFS)(From ~12 months to up to ~68 months)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score(Baseline, Up to ~68 months)
- Pathologic Complete Response (pCR) Rate(Up to ~47 months)
- Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)(Up to ~68 months)
- Change From Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)(Baseline, Up to ~68 months)
- Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS)(Baseline, Up to ~68 months)
- Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score (Items 6-7)(Baseline, Up to ~68 months)
- Overall Survival (OS)(Up to ~68 months)
- Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)(Up to ~68 months)
- Number of Participants Experiencing Perioperative Complications(Up to ~68 months)