Clinical Trials /

A Study of MK- 6482 in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)

NCT04489771

Description:

This study will compare the efficacy and safety of two doses of MK-6482 in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that the higher dose of MK-6482 is superior to the standard dose in terms of objective response rate (ORR).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MK- 6482 in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)
  • Official Title: Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 6482-013
  • SECONDARY ID: 2020-001907-18
  • SECONDARY ID: MK-6482-013
  • NCT ID: NCT04489771

Conditions

  • Carcinoma, Renal Cell

Interventions

DrugSynonymsArms
MK-6482Dose A (standard dose)

Purpose

This study will compare the efficacy and safety of two doses of MK-6482 in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that the higher dose of MK-6482 is superior to the standard dose in terms of objective response rate (ORR).

Trial Arms

NameTypeDescriptionInterventions
Dose A (standard dose)ExperimentalParticipants receive Dose A (standard dose) of MK-6482 by oral administration, once a day (QD), until disease progression or discontinuation.
  • MK-6482
Dose B (higher dose)ExperimentalParticipants receive Dose B (higher dose) of MK-6482 by oral administration, QD, until disease progression or discontinuation.
  • MK-6482

Eligibility Criteria

        Inclusion Criteria:

          -  Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear
             cell component

          -  Has measurable disease per RECIST 1.1 as assessed by BICR

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

          -  Has had disease progression on or after having received first-line systemic treatment
             for locally advanced or metastatic RCC with prior anti-programmed cell death 1 ligand
             1 (PD-1/L1) plus anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) combination
             OR anti-PD-1/L1 plus a vascular endothelial growth factor-tyrosine kinase inhibitor
             (VEGF-TKI) combination

          -  Has received no more than 3 prior systemic regimens for locally advanced or metastatic
             RCC

          -  Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days
             prior to the first dose of study intervention

          -  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

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

        Exclusion Criteria:

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

          -  Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent
             supplemental oxygen, or requires chronic supplemental oxygen

          -  Has a 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

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

          -  Has clinically significant cardiac disease, including unstable angina, acute
             myocardial infarction ≤6 months from Day 1 of study drug administration or New York
             Heart Association Class III or IV congestive heart failure

          -  Has moderate to severe hepatic impairment (Child-Pugh B or C)

          -  Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor
             [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant
             erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention

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

          -  Is unable to swallow orally administered medication or has a gastrointestinal disorder
             affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)

          -  Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any
             component of the study intervention (MK-6482) formulations

          -  Has received prior treatment with MK-6482 or another hypoxia-inducible factor (HIF)-2α
             inhibitor

          -  Has received any type of small molecule kinase inhibitor (including investigational
             kinase inhibitor) ≤2 weeks before randomization

          -  Has received any type of systemic anticancer antibody (including investigational
             antibody) ≤4 weeks before randomization

          -  Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention.
             Participants must have recovered from all radiation-related toxicities and not require
             corticosteroids

          -  Has had major surgery ≤3 weeks prior to first dose of study intervention

          -  Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
             moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4
             that cannot be discontinued for the duration of the study

          -  Is currently participating in a study of an investigational agent or is currently
             using an investigational device

          -  Has an active infection requiring systemic therapy

          -  Has active tuberculosis (TB)

          -  Has a diagnosis of immunodeficiency

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

          -  Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection

          -  Has a 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 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: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 48 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.

Secondary 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 48 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.
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 48 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:Clinical Benefit Rate (CBR) 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 48 months
Safety Issue:
Description:CBR 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) or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) ≥6 months per RECIST 1.1. The percentage of participants with CBR will be presented.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 48 months
Safety Issue:
Description:The time from randomization to death due to any cause.
Measure:Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame:Up to approximately 48 months
Safety Issue:
Description:An adverse event (AE) is defined as 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 one or more AEs will be presented.
Measure:Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Time Frame:Up to approximately 48 months
Safety Issue:
Description:An adverse event (AE) is defined as 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.
Measure:Maximum Plasma Concentration (Cmax) of MK-6482
Time Frame:Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only
Safety Issue:
Description:Blood samples will be obtained at designated time points for the determination of the Cmax of MK-6482.
Measure:Trough Plasma Concentration (Ctrough) of MK-6482
Time Frame:Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only
Safety Issue:
Description:Blood samples will be obtained at designated time points for the determination of the Ctrough of MK-6482.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Hypoxia inducible factor (HIF)
  • Hypoxia inducible factor 1B (HIF-1B)
  • Hypoxia inducible factor 2 alpha (HIF-2 alpha)
  • Hypoxia inducible factor 2α (HIF-2α)
  • Renal Cell Carcinoma (RCC)
  • Kidney cancer

Last Updated

September 22, 2020