A Phase 3, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)
概览
- 阶段
- 3 期
- 干预措施
- Pembrolizumab
- 疾病 / 适应症
- Renal Cell Carcinoma
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 994
- 试验地点
- 251
- 主要终点
- Disease-free Survival (DFS) as Assessed by the Investigator
- 状态
- 已完成
- 最后更新
- 上个月
概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component.
The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.
详细描述
Participants will be assigned to receive study treatment until disease recurrence, unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the participant, noncompliance with study treatment or procedural requirements, administrative reasons requiring cessation of treatment, or until the participant has received 17 cycles of study treatment (approximately 1 year). Each cycle is 3 weeks long. With Protocol Amendment 02 (dated 04 Sep 2019), the secondary study objectives for the evaluation of pharmacokinetic (PK) parameters and the presence of pembrolizumab antidrug antibodies (ADA) were reclassified as tertiary study objectives.
研究者
入排标准
入选标准
- •Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
- •Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment
- •Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment
- •Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
- •Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
- •High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0
- •M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous)
- •Has received no prior systemic therapy for advanced RCC
- •Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins
- •Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization
排除标准
- •Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization
- •Has received prior radiotherapy for RCC
- •Has pre-existing brain or bone metastatic lesions
- •Has residual thrombus post nephrectomy in the vena renalis or vena cava
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed
- •Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy
- •Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- •Has an active infection requiring systemic therapy
- •Has a history of, or is currently on, dialysis
研究组 & 干预措施
Pembrolizumab
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
干预措施: Pembrolizumab
Placebo
Participants receive placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles (up to approximately 1 year).
干预措施: Placebo
结局指标
主要结局
Disease-free Survival (DFS) as Assessed by the Investigator
时间窗: Up to approximately 42 months (database cutoff date 14 Dec 2020)
DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastasis status (M0 versus M1 no evidence of disease (NED) by investigator) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 versus 1), United States (US) participant (Yes versus No) within M0 group by investigator was used to report hazard ratio (HR) and 95% confidence intervals (CIs).
次要结局
- Number of Participants Who Experienced an Adverse Event (AE)(Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 13 months); Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 15 months))
- Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR)(Up to approximately 72 months)
- DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator(Up to approximately 72 months)
- Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score(Baseline and Week 52)
- Overall Survival (OS)(Up to approximately 72 months)
- Number of Participants Who Discontinued Study Drug Due to an AE(Up to approximately 12 months)
- First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator(Up to approximately 72 months)
- OS According to Participant PD-L1 Expression Status (Positive, Negative)(Up to approximately 72 months)
- Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score(Baseline and Week 52)
- Second Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator(Up to approximately 72 months)