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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04489771
Recruitment Status : Recruiting
First Posted : July 28, 2020
Last Update Posted : November 26, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

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

The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR).


Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: Belzutifan Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma
Actual Study Start Date : September 13, 2020
Estimated Primary Completion Date : October 4, 2025
Estimated Study Completion Date : October 4, 2025


Arm Intervention/treatment
Experimental: Dose A (standard dose)
Participants receive Dose A (standard dose) of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.
Drug: Belzutifan
Oral administration
Other Name: MK-6482

Experimental: Dose B (higher dose)
Participants receive Dose B (higher dose) of belzutifan by oral administration, QD, until disease progression or discontinuation.
Drug: Belzutifan
Oral administration
Other Name: MK-6482




Primary 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 48 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.


Secondary Outcome Measures :
  1. 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 ]
    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. 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 ]
    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. 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 ]
    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.

  4. Overall Survival (OS) [ Time Frame: Up to approximately 48 months ]
    The time from randomization to death due to any cause.

  5. Number of Participants Who Experience One or More Adverse Events (AEs) [ Time Frame: Up to approximately 48 months ]
    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.

  6. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 48 months ]
    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.

  7. Maximum Plasma Concentration (Cmax) of belzutifan [ Time Frame: Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only ]
    Blood samples will be obtained at designated time points for the determination of the Cmax of belzutifan.

  8. Trough Plasma Concentration (Ctrough) of belzutifan [ Time Frame: Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only ]
    Blood samples will be obtained at designated time points for the determination of the Ctrough of belzutifan.



Information from the National Library of Medicine

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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:

  • 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 (belzutifan) formulations
  • Has received prior treatment with belzutifan 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

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): NCT04489771


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04489771    
Other Study ID Numbers: 6482-013
2020-001907-18 ( EudraCT Number )
MK-6482-013 ( Other Identifier: Merck )
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: November 26, 2020
Last Verified: November 2020
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
Keywords provided by Merck Sharp & Dohme Corp.:
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
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
Kidney Diseases
Urologic Diseases