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A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022)

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ClinicalTrials.gov Identifier: NCT05239728
Recruitment Status : Recruiting
First Posted : February 15, 2022
Last Update Posted : January 30, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE February 4, 2022
First Posted Date  ICMJE February 15, 2022
Last Update Posted Date January 30, 2023
Actual Study Start Date  ICMJE March 15, 2022
Estimated Primary Completion Date October 25, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2022)
Disease-Free Survival (DFS) [ Time Frame: Up to approximately 66 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2022)
  • Overall Survival (OS) [ Time Frame: Up to approximately 94 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Up to approximately 66 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) [ Time Frame: Up to approximately 66 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 [ Time Frame: Baseline (Day 1) and Up to approximately 66 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 score will be presented.
  • Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score [ Time Frame: Baseline (Day 1) and Up to approximately 66 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 [ Time Frame: Baseline (Day 1) and Up to approximately 66 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 scores 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 [ Time Frame: Baseline (Day 1) and Up to approximately 66 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022)
Official Title  ICMJE A Multicenter, Double-blind, Randomized Phase 3 Study to Compare the Efficacy and Safety of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab, in the Adjuvant Treatment of Clear Cell Renal Cell Carcinoma (ccRCC) Post Nephrectomy (MK-6482-022)
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Clear Cell Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Belzutifan
    Three 40 mg tablets given as a single oral 120 mg dose.
    Other Names:
    • MK-6482
    • PT2977
    • WELIREG™
  • Biological: Pembrolizumab
    400 mg via IV infusion
    Other Names:
    • MK-3475
    • Keytruda®
  • Drug: Placebo
    Oral tablet
Study Arms  ICMJE
  • Experimental: Belzutifan + Pembrolizumab
    Participants receive belzutifan 120 mg orally once daily (QD) for up to approximately 54 weeks PLUS pembrolizumab 400 mg via intravenous (IV) infusion once every 6 weeks (Q6W) for up to 9 administrations (up to approximately 54 weeks).
    Interventions:
    • Drug: Belzutifan
    • Biological: Pembrolizumab
  • Experimental: Placebo + Pembrolizumab
    Participants receive placebo orally QD for up to approximately 54 weeks PLUS pembrolizumab 400 mg via IV infusion once Q6W for up to 9 administrations (up to approximately 54 weeks).
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 4, 2022)
1600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 25, 2030
Estimated Primary Completion Date October 25, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Exclusion Criteria:

  • Has had a major surgery, other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization
  • Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
  • Has clinically significant cardiovascular disease within 6 months from first dose of study intervention
  • Has other clinically significant disorders such as: serious active nonhealing wound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis
  • Has preexisting brain or bone metastatic lesions
  • Has received prior systemic therapy for RCC
  • Has received prior radiotherapy for RCC
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines are allowed
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  • Has a known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years
  • 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 history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection, requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection, a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has had an allogenic tissue/solid organ transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czechia,   Finland,   France,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Poland,   Singapore,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05239728
Other Study ID Numbers  ICMJE 6482-022
MK-6482-022 ( Other Identifier: Merck )
LITESPARK-022 ( Other Identifier: Merck )
jRCT2051220030 ( Registry Identifier: jRCT )
2021-003436-92 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP