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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04586231
Recruitment Status : Active, not recruiting
First Posted : October 14, 2020
Last Update Posted : May 6, 2024
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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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.


Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: Belzutifan Drug: Lenvatinib Drug: Cabozantinib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 708 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 25, 2021
Estimated Primary Completion Date : December 23, 2024
Estimated Study Completion Date : December 23, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Belzutifan + Lenvatinib
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
 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
Active Comparator: Cabozantinib
Cabozantinib 60 mg orally once a day
 Drug: Cabozantinib
Tablet available in 20 mg, 40 mg and 60 mg dosages
Other Names:
  • Cabometyx
  • Cometriq
  • XL184
  • BMS-907351


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Overall Survival (OS) [ Time Frame: Up to approximately 44 months ]
    OS is defined as time from randomization to death due to any cause.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 or neoadjuvant/adjuvant 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 including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
  • Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/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 they are 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586231


Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Eisai Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04586231    
Other Study ID Numbers: 6482-011
MK-6482-011 ( Other Identifier: Merck )
jRCT2031210311 ( Other Identifier: jRCT(Japan Registry of Clinical Trials) )
2020-002075-35 ( EudraCT Number )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: May 6, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Lenvatinib
Belzutifan
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action