<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04489771</url>
  </required_header>
  <id_info>
    <org_study_id>6482-013</org_study_id>
    <secondary_id>MK-6482-013</secondary_id>
    <secondary_id>2020-001907-18</secondary_id>
    <nct_id>NCT04489771</nct_id>
  </id_info>
  <brief_title>A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)</brief_title>
  <official_title>Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare the efficacy and safety of two doses of belzutifan in participants&#xD;
      with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.&#xD;
&#xD;
      The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose&#xD;
      in terms of objective response rate (ORR).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 13, 2020</start_date>
  <completion_date type="Anticipated">October 4, 2025</completion_date>
  <primary_completion_date type="Actual">February 10, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <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)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <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)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <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)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <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)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <description>The time from randomization to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experience One or More Adverse Events (AEs)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)</measure>
    <time_frame>Up to approximately 48 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of belzutifan</measure>
    <time_frame>Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only</time_frame>
    <description>Blood samples will be obtained at designated time points for the determination of the Cmax of belzutifan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Plasma Concentration (Ctrough) of belzutifan</measure>
    <time_frame>Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only</time_frame>
    <description>Blood samples will be obtained at designated time points for the determination of the Ctrough of belzutifan.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">154</enrollment>
  <condition>Carcinoma, Renal Cell</condition>
  <arm_group>
    <arm_group_label>Dose A (standard dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Dose A (standard dose) of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose B (higher dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Dose B (higher dose) of belzutifan by oral administration, QD, until disease progression or discontinuation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Belzutifan</intervention_name>
    <description>Oral administration</description>
    <arm_group_label>Dose A (standard dose)</arm_group_label>
    <arm_group_label>Dose B (higher dose)</arm_group_label>
    <other_name>MK-6482</other_name>
    <other_name>PT2977</other_name>
    <other_name>WELIREG™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear&#xD;
             cell component&#xD;
&#xD;
          -  Has measurable disease per RECIST 1.1 as assessed by BICR&#xD;
&#xD;
          -  Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy&#xD;
             of a tumor lesion not previously irradiated&#xD;
&#xD;
          -  Has experienced disease progression on or after systemic treatment with an&#xD;
             anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or&#xD;
             metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with&#xD;
             other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or&#xD;
             vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI).&#xD;
             The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy&#xD;
&#xD;
          -  Has received no more than 3 prior systemic regimens for locally advanced or metastatic&#xD;
             RCC&#xD;
&#xD;
          -  Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC&#xD;
&#xD;
          -  Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the&#xD;
             exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment&#xD;
             or hormone replacement&#xD;
&#xD;
          -  Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days&#xD;
             prior to the first dose of study intervention&#xD;
&#xD;
          -  A male participant is eligible to participate if he is abstinent from heterosexual&#xD;
             intercourse or agrees to use contraception during the intervention period and for at&#xD;
             least 7 days after the last dose of study intervention&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant, not&#xD;
             breastfeeding, and at least 1 of the following conditions applies: Not a (woman of&#xD;
             childbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptive&#xD;
             guidance during the intervention period and for at least 30 days after the last dose&#xD;
             of study intervention&#xD;
&#xD;
          -  A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within&#xD;
             24 hours before the first dose of study intervention&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has hypoxia (a pulse oximeter reading &lt;92% at rest), requires intermittent&#xD;
             supplemental oxygen, or requires chronic supplemental oxygen&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or has required active treatment&#xD;
             within the past 3 years except for basal cell carcinoma of the skin, squamous cell&#xD;
             carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer&#xD;
             in situ] that have undergone potentially curative therapy&#xD;
&#xD;
          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Has clinically significant cardiac disease, including unstable angina, acute&#xD;
             myocardial infarction ≤6 months from Day 1 of study drug administration or New York&#xD;
             Heart Association Class III or IV congestive heart failure&#xD;
&#xD;
          -  Has moderate to severe hepatic impairment (Child-Pugh B or C)&#xD;
&#xD;
          -  Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor&#xD;
             [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant&#xD;
             erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention&#xD;
&#xD;
          -  Has a known psychiatric or substance abuse disorder that would interfere with&#xD;
             cooperation with the requirements of the study&#xD;
&#xD;
          -  Is unable to swallow orally administered medication or has a gastrointestinal disorder&#xD;
             affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)&#xD;
&#xD;
          -  Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any&#xD;
             component of the study intervention (belzutifan) formulations&#xD;
&#xD;
          -  Has received prior treatment with belzutifan or another hypoxia-inducible factor&#xD;
             (HIF)-2α inhibitor&#xD;
&#xD;
          -  Has received any type of small molecule kinase inhibitor (including investigational&#xD;
             kinase inhibitor) ≤2 weeks before randomization&#xD;
&#xD;
          -  Has received any type of systemic anticancer antibody (including investigational&#xD;
             antibody) ≤4 weeks before randomization&#xD;
&#xD;
          -  Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention.&#xD;
             Participants must have recovered from all radiation-related toxicities and not require&#xD;
             corticosteroids&#xD;
&#xD;
          -  Has had major surgery ≤3 weeks prior to first dose of study intervention&#xD;
&#xD;
          -  Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or&#xD;
             moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4&#xD;
             that cannot be discontinued for the duration of the study&#xD;
&#xD;
          -  Is currently participating in a study of an investigational agent or is currently&#xD;
             using an investigational device&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy&#xD;
&#xD;
          -  Has active tuberculosis (TB)&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the participant's&#xD;
             participation for the full duration of the study, or is not the best interest of the&#xD;
             participant to participate, in the opinion of the treating investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown University Medical Center ( Site 0002)</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023)</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute - St. Matthews ( Site 0025)</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weinberg Cancer Institute at Franklin Square ( Site 0007)</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Partners of Nebraska ( Site 0003)</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012)</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology P.C ( Site 0028)</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute ( Site 0038)</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center ( Site 0026)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Cancer Center Oncology Clinic ( Site 0031)</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT West Cancer Center ( Site 0032)</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Urology Associates ( Site 0015)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center at Dallas ( Site 0004)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Medical Center - Temple ( Site 0013)</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute ( Site 0037)</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Schar Cancer Institute ( Site 0001)</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blue Ridge Cancer Care - Roanoke ( Site 0017)</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kadlec Clinic Hematology and Oncology ( Site 0008)</name>
      <address>
        <city>Kennewick</city>
        <state>Washington</state>
        <zip>99336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Macquarie University ( Site 1007)</name>
      <address>
        <city>Macquarie University</city>
        <state>New South Wales</state>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Health - Box Hill Hospital ( Site 1003)</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Health Frankston Hospital ( Site 1001)</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GZA Sint Augustinus ( Site 2003)</name>
      <address>
        <city>Wilrijk</city>
        <state>Antwerpen</state>
        <zip>2610</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Hopital de Charleroi ( Site 2005)</name>
      <address>
        <city>Charleroi</city>
        <state>Hainaut</state>
        <zip>6000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Liege ( Site 2002)</name>
      <address>
        <city>Liège</city>
        <state>Liege</state>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent ( Site 2004)</name>
      <address>
        <city>Gent</city>
        <state>Oost-Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven ( Site 2001)</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams-Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital of Athens &quot;Alexandra&quot; ( Site 1102)</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 28</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Athens University Hospital ATTIKON ( Site 1100)</name>
      <address>
        <city>Chaidari</city>
        <state>Attiki</state>
        <zip>12 462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Larissa ( Site 1101)</name>
      <address>
        <city>Larissa</city>
        <state>Thessalia</state>
        <zip>411 10</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Hospital ( Site 9053)</name>
      <address>
        <city>Cork</city>
        <zip>T12 DC4A</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tallaght University Hospital ( Site 9051)</name>
      <address>
        <city>Dublin</city>
        <zip>D24 NR0A</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soroka Medical Center ( Site 4004)</name>
      <address>
        <city>Beer Sheva</city>
        <zip>8410101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center ( Site 4001)</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center ( Site 4002)</name>
      <address>
        <city>Petach Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center ( Site 4003)</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6202AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord-Holland</state>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala klinieken ( Site 5002)</name>
      <address>
        <city>Zwolle</city>
        <state>Overijssel</state>
        <zip>8025 AB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC ( Site 5000)</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid-Holland</state>
        <zip>3015 GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Utrecht ( Site 5004)</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Oncology Hospital No. 1 ( Site 6004)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>129090</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001)</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center of specialized types medical care-Oncology ( Site 6002)</name>
      <address>
        <city>Saint-Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free London NHS Foundation Trust ( Site 9003)</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust ( Site 9004)</name>
      <address>
        <city>London</city>
        <state>London, City Of</state>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Churchill Hospital ( Site 9000)</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001)</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Greece</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trials Information</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>April 10, 2023</last_update_submitted>
  <last_update_submitted_qc>April 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypoxia inducible factor (HIF)</keyword>
  <keyword>Hypoxia inducible factor 1B (HIF-1B)</keyword>
  <keyword>Hypoxia inducible factor 2 alpha (HIF-2 alpha)</keyword>
  <keyword>Hypoxia inducible factor 2α (HIF-2α)</keyword>
  <keyword>Renal Cell Carcinoma (RCC)</keyword>
  <keyword>Kidney cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Belzutifan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489771
org study id: 6482-013
secondary id: MK-6482-013
secondary id: 2020-001907-18
nct id: NCT04489771
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
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
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: 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
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
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
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
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
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
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 belzutifan
time frame: Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only
description: Blood samples will be obtained at designated time points for the determination of the Cmax of belzutifan.
measure: 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
description: Blood samples will be obtained at designated time points for the determination of the Ctrough of belzutifan.
arm group label: Dose A (standard dose)
arm group type: Experimental
description: Participants receive Dose A (standard dose) of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.
arm group label: Dose B (higher dose)
arm group type: Experimental
description: Participants receive Dose B (higher dose) of belzutifan by oral administration, QD, until disease progression or discontinuation.
intervention type: Drug
intervention name: Belzutifan
description: Oral administration
arm group label: Dose A (standard dose)
arm group label: Dose B (higher dose)
other name: MK-6482
other name: PT2977
other name: WELIREG™
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: Greece
country: Ireland
country: Israel
country: Netherlands
country: Russian Federation
country: United Kingdom
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trials Information
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Belzutifan
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php