Carcinoma, Renal Cell
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Hypoxia inducible factor 2 alpha (HIF-2 alpha), Hypoxia inducible factor 2α (HIF-2α)
Brief summary
The purpose of this study is to assess the efficacy and safety of oral belzutifan (MK-6482) plus intravenous (IV) pembrolizumab (MK-3475) compared to placebo plus pembrolizumab, in the adjuvant treatment of Clear Cell Renal Cell Carcinoma (ccRCC) post nephrectomy. The primary study hypothesis is that belzutifan plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS).
Interventions
DRUGBelzutifan
Three 40 mg tablets given as a single oral 120 mg dose.
BIOLOGICALPembrolizumab
400 mg via IV infusion
DRUGPlacebo
Oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has a histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without sarcomatoid features * Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading: 1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0 2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0 3. 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, ≤2 years from nephrectomy (metachronous) * Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants * Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days before randomization. * Male participants must agree to continue contraception at least 7 days after the last dose of belzutifan/placebo * 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 pembrolizumab or at least 30 days after last dose of belzutifan/placebo, whichever occurs last * Has adequate organ function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) | Up to approximately 54 months | DFS is defined as the time from randomization to the first documented local recurrence, or occurrence of distant kidney cancer metastasis(es) as assessed by investigator, or death due to any cause, whichever occurs first. The DFS for all participants will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 89 months | OS is defined as the time from randomization to death due to any cause. |
| Number of Participants Who Experience at Least One Adverse Event (AE) | Up to approximately 66 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 54 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued the study due to an AE will be reported. |
| Disease Recurrence-Specific Survival 1 (DRSS1) | Up to approximately 54 months | DRSS1 is defined as the time from randomization to the first documented local recurrence of RCC as assessed by the investigator. For DRSS1, only local recurrence is counted as an event. |
| Disease Recurrence-Specific Survival 2 (DRSS2) | Up to approximately 54 months | DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or occurrence of distant kidney cancer metastasis(es) with visceral lesion, whichever occurs first, as assessed by investigator. |
| Change From Baseline in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score | Baseline (Day 1) and up to approximately 36 months | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of participants with cancer. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented. |
| Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score | Baseline (Day 1) and up to approximately 36 months | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. Change from baseline in the score of EORTC QLQ-C30 Items 1-5 will be presented. |
| Change From Baseline in Role Functioning Using the EORTC QLQ-C30 Items 6 and 7 Score | Baseline (Day 1) and up to approximately 36 months | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher score indicate a worse level of function. Change from baseline in the score of EORTC QLQ-C30 Items 6-7 will be presented. |
| Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score | Baseline (Day 1) and up to approximately 36 months | The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. Change from baseline in the score of FKSI-DRS Items 1-9 will be presented. |
Countries
Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed