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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04489771
Collaborator
(none)
150
48
2
60.7
3.1
0.1

Study Details

Study Description

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
Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Sep 13, 2020
Anticipated Primary Completion Date :
Oct 4, 2025
Anticipated Study Completion Date :
Oct 4, 2025

Arms and Interventions

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 Names:
  • MK-6482
  • PT2977
  • WELIREG™
  • 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 Names:
  • MK-6482
  • PT2977
  • WELIREG™
  • Outcome Measures

    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) [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) [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) [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) [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) [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) [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) [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 [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 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI). The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy

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

    • Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC

    • Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement

    • 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 7 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:
    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Georgetown University Medical Center ( Site 0002) Washington District of Columbia United States 20007
    2 Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023) Miami Florida United States 33136
    3 Norton Cancer Institute - St. Matthews ( Site 0025) Louisville Kentucky United States 40207
    4 Weinberg Cancer Institute at Franklin Square ( Site 0007) Baltimore Maryland United States 21237
    5 Cancer Partners of Nebraska ( Site 0003) Lincoln Nebraska United States 68510
    6 Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012) Omaha Nebraska United States 68130
    7 New York Oncology Hematology P.C ( Site 0028) Albany New York United States 12206
    8 Roswell Park Cancer Institute ( Site 0038) Buffalo New York United States 14263
    9 Fox Chase Cancer Center ( Site 0026) Philadelphia Pennsylvania United States 19111
    10 Sanford Cancer Center Oncology Clinic ( Site 0031) Sioux Falls South Dakota United States 57104
    11 UT West Cancer Center ( Site 0032) Germantown Tennessee United States 38138
    12 Urology Associates ( Site 0015) Nashville Tennessee United States 37209
    13 University of Texas Southwestern Medical Center at Dallas ( Site 0004) Dallas Texas United States 75390
    14 Baylor Scott & White Medical Center - Temple ( Site 0013) Temple Texas United States 76508
    15 Huntsman Cancer Institute ( Site 0037) Salt Lake City Utah United States 84112
    16 Inova Schar Cancer Institute ( Site 0001) Fairfax Virginia United States 22031
    17 Blue Ridge Cancer Care - Roanoke ( Site 0017) Roanoke Virginia United States 24014
    18 Kadlec Clinic Hematology and Oncology ( Site 0008) Kennewick Washington United States 99336
    19 Macquarie University ( Site 1007) Macquarie University New South Wales Australia 2109
    20 Eastern Health - Box Hill Hospital ( Site 1003) Box Hill Victoria Australia 3128
    21 Peninsula Health Frankston Hospital ( Site 1001) Frankston Victoria Australia 3199
    22 GZA Sint Augustinus ( Site 2003) Wilrijk Antwerpen Belgium 2610
    23 Grand Hopital de Charleroi ( Site 2005) Charleroi Hainaut Belgium 6000
    24 CHU de Liege ( Site 2002) Liège Liege Belgium 4000
    25 UZ Gent ( Site 2004) Gent Oost-Vlaanderen Belgium 9000
    26 UZ Leuven ( Site 2001) Leuven Vlaams-Brabant Belgium 3000
    27 General Hospital of Athens "Alexandra" ( Site 1102) Athens Attiki Greece 115 28
    28 Athens University Hospital ATTIKON ( Site 1100) Chaidari Attiki Greece 12 462
    29 University General Hospital of Larissa ( Site 1101) Larissa Thessalia Greece 411 10
    30 Cork University Hospital ( Site 9053) Cork Ireland T12 DC4A
    31 Tallaght University Hospital ( Site 9051) Dublin Ireland D24 NR0A
    32 Soroka Medical Center ( Site 4004) Beer Sheva Israel 8410101
    33 Rambam Medical Center ( Site 4001) Haifa Israel 3109601
    34 Rabin Medical Center ( Site 4002) Petach Tikva Israel 4941492
    35 Sourasky Medical Center ( Site 4003) Tel Aviv Israel 6423906
    36 Maastricht Universitair Medisch Centrum - MUMC ( Site 5001) Maastricht Limburg Netherlands 6202AZ
    37 Antoni van Leeuwenhoek Ziekenhuis ( Site 5003) Amsterdam Noord-Holland Netherlands 1066 CX
    38 Isala klinieken ( Site 5002) Zwolle Overijssel Netherlands 8025 AB
    39 Erasmus MC ( Site 5000) Rotterdam Zuid-Holland Netherlands 3015 GD
    40 Universitair Medisch Centrum Utrecht ( Site 5004) Utrecht Netherlands 3584 CX
    41 Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site Moscow Moskva Russian Federation 117997
    42 City Clinical Oncology Hospital No. 1 ( Site 6004) Moscow Moskva Russian Federation 129090
    43 Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001) Saint Petersburg Sankt-Peterburg Russian Federation 197758
    44 Clinical Research Center of specialized types medical care-Oncology ( Site 6002) Saint-Petersburg Sankt-Peterburg Russian Federation 197758
    45 Royal Free London NHS Foundation Trust ( Site 9003) London England United Kingdom NW3 2QG
    46 Imperial College Healthcare NHS Trust ( Site 9004) London London, City Of United Kingdom W6 8RF
    47 Churchill Hospital ( Site 9000) Oxford Oxfordshire United Kingdom OX3 7LE
    48 Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001) Nottingham United Kingdom NG5 1PB

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT04489771
    Other Study ID Numbers:
    • 6482-013
    • MK-6482-013
    • 2020-001907-18
    First Posted:
    Jul 28, 2020
    Last Update Posted:
    Jul 11, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 11, 2022