A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-866)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 907
- 试验地点
- 340
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
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
- •Have adequate organ function.
- •Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.
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.
研究组 & 干预措施
Pembrolizumab + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.
干预措施: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) (Procedure)
Placebo + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.
干预措施: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) (Procedure)
Placebo + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.
干预措施: Placebo (Drug)
Pembrolizumab + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.
干预措施: Gemcitabine (Drug)
Pembrolizumab + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.
干预措施: Cisplatin (Drug)
Placebo + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.
干预措施: Gemcitabine (Drug)
Placebo + Gemcitabine + Cisplatin + Surgery
Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: Up to approximately 60 months
EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery; failure to undergo RC surgery in participants with residual disease and any radiographical disease present; gross residual disease left behind at the time of surgery; local or distant recurrence based on investigator assessments and/or biopsy, or death due to any cause.
次要结局
- Pathologic Complete Response (pCR) Rate(Up to approximately 72 months)
- Overall Survival (OS)(Up to approximately 72 months)
- Disease-Free Survival (DFS)(From approximately 20 weeks up to approximately 72 months)
- Pathologic Downstaging (pDS) Rate(Up to approximately 72 months)
- TTD in EQ-5D-5L VAS(Up to approximately 72 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 12 months)
- Number of Participants Who Experienced Perioperative Complications(Up to approximately 12 months)
- Change in Patient-Reported Outcomes from Baseline in Total Score of Functional Assessment of Cancer Therapy - General (FACT-G)(Baseline, Up to approximately 72 months)
- Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)(Baseline, Up to approximately 72 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 72 months)
- Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys)(Baseline, Up to approximately 72 months)
- Time to Deterioration (TTD) in the Total Score of FACT-G(Up to approximately 72 months)
- Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)(Baseline, Up to approximately 72 months)