A Phase 3, Randomized, Study of Neoadjuvant and Adjuvant Nivolumab Plus Bempegaldesleukin (NKTR-214), Versus Nivolumab Alone Versus Standard of Care in Participants With Muscle-Invasive Bladder Cancer (MIBC) Who Are Cisplatin Ineligible
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 114
- 试验地点
- 218
- 主要终点
- Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care
研究概览
简要总结
The purpose of the study is to see if treatment with nivolumab plus bempegaldesleukin or nivolumab alone, before and after surgery to remove the bladder, is more effective than surgery alone in participants with high-risk urothelial cancer, including muscle-invasive bladder cancer who are not able to receive cisplatin chemotherapy.
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
- •Urothelial carcinoma (UC) of the bladder, clinical stage T2-T4aN0, M0 or T1-T4aN1, M0, diagnosed at transurethral resection of bladder tumor (TURBT)
- •Must be deemed eligible for Radical Cystectomy (RC) by urologist, and must agree to undergo RC. For arms A and B, participants must agree to undergo RC after completion of neoadjuvant therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Cisplatin-ineligible participants will be defined by any one of the following criteria:
- •i) Impaired renal function (glomerular filtration rate [GFR] ≥ 30 but < 60 mL/min) ii) GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) iii) Common Terminology Criteria for Adverse Events (CTCAE) version 5, ≥ Grade 2 hearing loss (assessed per local SOC).
- •iv) CTCAE version 5, ≥ Grade 2 peripheral neuropathy.
- •Documented Left Ventricular Ejection Fraction (LVEF) more than 45%
排除标准
- •Clinical evidence of ≥ N2 or metastatic bladder cancer
- •Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is not permitted. Prior Bacillus Calmette-Guerin (BCG) or other intravesicular treatment of non-muscle invasive bladder cancer (NMIBC) is permitted if completed at least 6 weeks prior to initiating study treatment.
- •Evidence of urothelial carcinoma (UC) in upper urinary tracts (ureters or renal pelvis) or history of previous MIBC
- •History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA(cerebrovascular accident)/TIA (Transient ischemic attack) arterial thromboembolic event
- •Known cardiovascular history, including unstable or deteriorating cardiac disease within the previous 12 months (including unstable angina or myocardial infarction, congestive heart failure or uncontrolled clinically significant arrhythmias)
- •Other protocol-defined inclusion/exclusion criteria apply
结局指标
主要结局
Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care
时间窗: From randomization up to first EFS event (up to approximately 30 months)
Event Free Survival (EFS) is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence based on blinded independent committee review (BICR) assessments, or death due to any cause. Participants who did not have an EFS event will be censored on the date of their last evaluable tumor assessment (imaging or biopsy) or at the date of radical surgery whichever occur last. Participants who did not have any baseline tumor assessments (imaging or biopsy) and did not undergo radical cystectomy for other reason than worsening/progression of disease will be censored on their date of randomization. Participants who did not have any on study tumor assessments (imaging or biopsy) and did not die will be censored on their date of radical cystectomy (or randomization date if no radical cystectomy performed).
Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care
时间窗: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)
Pathologic Complete Response (pCR) is defined as the percentage of randomized participants with absence of any cancer in pathology specimens after radical cystectomy, based on blinded independent pathology review (BIPR). Participants who do not undertake surgery will be counted as non-pCR.
次要结局
- Pathologic Complete Response (pCR) Rate - Nivolumab Compared to Standard of Care(From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months))
- The Number of Participants Experiencing Adverse Events (AEs)(from first dose to 100 days following last dose (up to approximately 20 months))
- The Number of Participants Experiencing Serious Adverse Events (SAEs)(from first dose to 100 days following last dose (up to approximately 20 months))
- The Number of Participants Experiencing Immune-Mediated Adverse Events (IMAEs)(from first dose to 100 days following last dose (up to approximately 20 months))
- Worst Grade Clinical Laboratory Values(From first dose to 100 days following last dose (up to approximately 20 months))
- Event Free Survival (EFS) - Nivolumab Compared to Standard of Care(From randomization up to first EFS event (up to approximately 30 months))
- Overall Survival (OS)(From randomization to study completion, up to approximately 40 months)
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation(from first dose to 100 days following last dose (up to approximately 20 months))