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A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)

NCT04736706

Description:

The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)
  • Official Title: An Open-label, Randomized Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or MK-1308A in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, as First-Line Treatment in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)

Clinical Trial IDs

  • ORG STUDY ID: 6482-012
  • SECONDARY ID: 2020-002216-52
  • SECONDARY ID: MK-6482-012
  • NCT ID: NCT04736706

Conditions

  • Carcinoma, Renal Cell

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®Pembrolizumab + Belzutifan + Lenvatinib
BelzutifanMK-6482, PT2977Pembrolizumab + Belzutifan + Lenvatinib
Pembrolizumab/QuavonlimabMK-1308APembrolizumab/Quavonlimab + Lenvatinib
LenvatinibMK-7902, E7080, LENVIMA®Pembrolizumab + Belzutifan + Lenvatinib

Purpose

The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + Belzutifan + LenvatinibExperimentalParticipants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to ~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
  • Pembrolizumab
  • Belzutifan
  • Lenvatinib
Pembrolizumab/Quavonlimab + LenvatinibExperimentalParticipants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
  • Pembrolizumab/Quavonlimab
  • Lenvatinib
Pembrolizumab + LenvatinibActive ComparatorParticipants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
  • Pembrolizumab
  • Lenvatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically confirmed diagnosis of RCC with clear cell component

          -  Has received no prior systemic therapy for advanced ccRCC

          -  Male participants are abstinent from heterosexual intercourse or agree to use
             contraception during and for at least 7 days after last dose of study intervention
             with belzutifan and lenvatinib

          -  Female participants are not pregnant or breastfeeding and are either not a woman of
             child-bearing potential (WOCBP) or use a contraceptive method that is highly effective
             or are abstinent from heterosexual intercourse during the intervention period and for
             at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30
             days after last dose of lenvatinib or belzutifan, whichever occurs last

          -  Has adequately controlled blood pressure with or without antihypertensive medications

          -  Has adequate organ function

          -  Participants receiving bone resorptive therapy must have therapy initiated at least 2
             weeks prior to randomization/allocation

        Exclusion Criteria:

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years

          -  Has had major surgery, other than nephrectomy plus resection of preexisting
             metastases, within 4 weeks prior to randomization

          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Has received prior radiotherapy within 2 weeks prior to first dose of study
             intervention

          -  Has hypoxia or requires intermittent supplemental oxygen or requires chronic
             supplemental oxygen

          -  Has clinically significant cardiac disease within 12 months from first dose of study
             intervention

          -  Has a history of interstitial lung disease

          -  Has symptomatic pleural effusion; a participant who is clinically stable following
             treatment of this condition is eligible

          -  Has preexisting gastrointestinal or non-gastrointestinal fistula

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior to the first dose
             of study treatment

          -  Has a known psychiatric or substance abuse disorder that would interfere with
             requirements of the study

          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of
             study drug; killed vaccines are allowed

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  Has a history of noninfectious pneumonitis that required steroids or has current
             pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a known history of human immunodeficiency virus (HIV) infection

          -  Has a known history of Hepatitis B

          -  Has radiographic evidence of intratumoral cavitation, encasement or invasion of a
             major blood vessel

          -  Has clinically significant history of bleeding within 3 months prior to randomization

          -  Has had an allogenic tissue/solid organ transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) According to 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 46 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 BICR based on RECIST 1.1 will be presented.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Time Frame:Up to approximately 46 months
Safety Issue:
Description:ORR is defined as the percentage of participants who have a complete response (CR: disappearance of all target lesions) or 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 BICR based on RECIST 1.1 will be presented.
Measure:Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time Frame:Up to approximately 66 months
Safety Issue:
Description:For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed 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 PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 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. The DOR as assessed by BICR based on RECIST 1.1 will be presented.
Measure:Number of Participants Who Experienced At least One Adverse Event (AE)
Time Frame:Up to approximately 66 months
Safety Issue:
Description: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. The number of participants who experience at least one AE will be presented.
Measure:Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame:Up to approximately 66 months
Safety Issue:
Description: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. The number of participants who discontinue study treatment due to an AE will be presented.

Details

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

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)
  • Hypoxia inducible factor (HIF)
  • Hypoxia inducible factor 1B (HIF-1B)
  • Hypoxia inducible factor 2 alpha (HIF-2 alpha)

Last Updated

May 24, 2021