Clinical Trials /

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

NCT04586231

Description:

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.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
  • Official Title: An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib for Second-line or Third-line Treatment in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

Clinical Trial IDs

  • ORG STUDY ID: 6482-011
  • SECONDARY ID: 2020-002075-35
  • SECONDARY ID: MK-6482-011
  • NCT ID: NCT04586231

Conditions

  • Carcinoma, Renal Cell

Interventions

DrugSynonymsArms
BelzutifanPT2977Belzutifan + Lenvatinib
LenvatinibLenvima, E7080, MK-7902Belzutifan + Lenvatinib
CabozantinibCabometyx, Cometriq, XL184, BMS-907351Cabozantinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Belzutifan + LenvatinibExperimentalBelzutifan 120 mg and lenvatinib 20 mg orally once a day
  • Belzutifan
  • Lenvatinib
CabozantinibActive ComparatorCabozantinib 60 mg orally once a day
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

          -  Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).

          -  Disease progression on or after having received systemic treatment for locally
             advanced or metastatic RCC with programmed cell death 1 ligand 1 (PD-1/L1).

          -  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 prior
             to the first dose of study intervention.

          -  Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated.

          -  Received no more than 2 prior systemic regimens for locally advanced or 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 5 days after the last dose of study intervention.

          -  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.

          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within
             24 hours before the first dose of study intervention.

          -  Adequately controlled blood pressure.

          -  Adequate organ function.

        Exclusion Criteria:

          -  Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to
             randomization.

          -  Hypoxia (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 [e.g., 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 12 months of first dose of study
             intervention.

          -  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.

          -  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.

          -  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.

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the participant's
             participation for the full duration of the study, or is not in the best interest of
             the participant to participate, in the opinion of the treating investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Number of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame:Up to approximately 44 months
Safety Issue:
Description: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.
Measure:Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame:Up to approximately 44 months
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Last Updated

December 2, 2020