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Trial record 1 of 1 for:    MK6482-011
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A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

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ClinicalTrials.gov Identifier: NCT04586231
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : July 26, 2022
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE October 9, 2020
First Posted Date  ICMJE October 14, 2020
Last Update Posted Date July 26, 2022
Actual Study Start Date  ICMJE February 25, 2021
Estimated Primary Completion Date December 23, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 34 months ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.
  • Overall Survival (OS) [ Time Frame: Up to approximately 44 months ]
    OS is defined as time from randomization to death due to any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 24 months ]
    ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.
  • Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 44 months ]
    For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review will be presented.
  • Number of Participants Who Experienced One or More Adverse Events (AEs) [ Time Frame: Up to approximately 44 months ]
    An adverse event (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.
  • Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 44 months ]
    An adverse event (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.
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) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Official Title  ICMJE An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy
Brief Summary

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.

The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Renal Cell
Intervention  ICMJE
  • Drug: Belzutifan
    Immediate-release 40 mg tablet
    Other Names:
    • PT2977
    • MK-6482
    • WELIREG™
  • Drug: Lenvatinib
    Capsule available in 4 mg and 10 mg dosages
    Other Names:
    • Lenvima
    • E7080
    • MK-7902
  • Drug: Cabozantinib
    Tablet available in 20 mg, 40 mg and 60 mg dosages
    Other Names:
    • Cabometyx
    • Cometriq
    • XL184
    • BMS-907351
Study Arms  ICMJE
  • Experimental: Belzutifan + Lenvatinib
    Belzutifan 120 mg and lenvatinib 20 mg orally once a day
    Interventions:
    • Drug: Belzutifan
    • Drug: Lenvatinib
  • Active Comparator: Cabozantinib
    Cabozantinib 60 mg orally once a day
    Intervention: Drug: Cabozantinib
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: October 9, 2020)
708
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 23, 2024
Estimated Primary Completion Date December 23, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
  • Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment with progression on or within 6 months of last dose.
  • Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
  • Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
  • Received no more than 2 prior systemic regimens.
  • Received only 1 prior antiPD-1/L1 therapy for adjuvant or locally advanced/metastatic RCC.
  • A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
  • Adequately controlled blood pressure.
  • Adequate organ function.

Exclusion Criteria:

  • A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
  • Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Clinically significant cardiac disease within 6 months of first dose of study intervention.
  • Prolongation of QTc interval to >480 ms.
  • Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
  • Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
  • Moderate to severe hepatic impairment.
  • History of significant bleeding within 3 months before randomization.
  • History of solid organ transplantation.
  • Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  • Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
  • Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
  • Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
  • Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
  • Prior treatment with lenvatinib.
  • Prior treatment with cabozantinib.
  • Currently participating in a study of an investigational agent or using an investigational device.
  • Active infection requiring systemic therapy.
  • History of human immunodeficiency virus (HIV) infection.
  • History of hepatitis B or known active hepatitis C infection.
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,   Austria,   Belgium,   Brazil,   Canada,   Colombia,   Finland,   France,   Germany,   Ireland,   Italy,   Japan,   Netherlands,   Poland,   Russian Federation,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04586231
Other Study ID Numbers  ICMJE 6482-011
MK-6482-011 ( Other Identifier: Merck )
jRCT2031210311 ( Other Identifier: jRCT(Japan Registry of Clinical Trials) )
2020-002075-35 ( 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 Eisai Inc.
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date July 2022

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