<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/NCT02974738</url>
  </required_header>
  <id_info>
    <org_study_id>6482-001</org_study_id>
    <secondary_id>PT2977-101</secondary_id>
    <secondary_id>MK-6482-001</secondary_id>
    <nct_id>NCT02974738</nct_id>
  </id_info>
  <brief_title>A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)</brief_title>
  <official_title>A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peloton Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peloton Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to identify the maximum tolerated dose (MTD) of&#xD;
      belzutifan Tablets and/or the recommended Phase 2 dose (RP2D) of belzutifan Tablets in&#xD;
      patients with advanced solid tumors&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of belzutifan Tablets, where&#xD;
      patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient&#xD;
      safety will be monitored with frequent physical examinations, vital sign measurements,&#xD;
      electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording&#xD;
      all adverse events (AEs). Blood will be obtained for analysis of the concentration of&#xD;
      belzutifan and to assess biomarkers.&#xD;
&#xD;
      Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 50 patients with&#xD;
      advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.&#xD;
&#xD;
      Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid&#xD;
      tumors may be enrolled. Up to 3 different tumor types may be included in this part of the&#xD;
      study.&#xD;
&#xD;
      Part 2A: A cohort of 25 patients with glioblastoma (GBM)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 7, 2016</start_date>
  <completion_date type="Anticipated">April 14, 2025</completion_date>
  <primary_completion_date type="Actual">January 12, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>maximum tolerated dose (MTD)</measure>
    <time_frame>3 Weeks</time_frame>
    <description>21-Day Dose Limiting Toxicity Observation Period per Dose Group</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <condition>Solid Tumor</condition>
  <condition>Solid Carcinoma</condition>
  <condition>Solid Tumor, Adult</condition>
  <condition>ccRCC</condition>
  <condition>RCC, Clear Cell Adenocarcinoma</condition>
  <condition>RCC</condition>
  <condition>Kidney Cancer</condition>
  <condition>Clear Cell Renal Cell Carcinoma</condition>
  <condition>Renal Cell Carcinoma, Metastatic</condition>
  <condition>Renal Cell Carcinoma Recurrent</condition>
  <condition>Renal Cell Carcinoma, Clear Cell Adenocarcinoma</condition>
  <condition>Glioblastoma</condition>
  <condition>Glioblastoma, Adult</condition>
  <condition>GBM</condition>
  <condition>Glioblastoma Multiforme</condition>
  <arm_group>
    <arm_group_label>Part 1A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: PART 1A: Belzutifan for the treatment of advanced solid tumors&#xD;
Belzutifan inhibits HIF-2α and is a novel approach to treatment of solid tumors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: PART 1B: Belzutifan for the treatment of advanced ccRCC&#xD;
Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Part 2: Belzutifan for the treatment of other specified solid tumors&#xD;
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Part 2A: Belzutifan for the treatment of patients with recurrent GBM who have been previously treated with radiation therapy and temozolomide&#xD;
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Belzutifan</intervention_name>
    <description>Belzutifan is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis</description>
    <arm_group_label>Part 1A</arm_group_label>
    <arm_group_label>Part 1B</arm_group_label>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_label>Part 2A</arm_group_label>
    <other_name>PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482</other_name>
    <other_name>WELIREG™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a diagnosis of locally advanced or metastatic solid tumor&#xD;
&#xD;
          -  Is of age ≥ 18 years&#xD;
&#xD;
          -  Has a life expectancy of ≥ 6 months&#xD;
&#xD;
          -  Has adequate organ function&#xD;
&#xD;
          -  If a female patient, must not be pregnant or breastfeeding and not a woman of&#xD;
             childbearing potential (WOCBP) OR a WOCBP who uses contraception or is abstinent from&#xD;
             heterosexual intercourse during the study and for a minimum of 30 days after the last&#xD;
             study drug administration, or if a male patient, must be abstinent from heterosexual&#xD;
             intercourse OR agree to use contraception&#xD;
&#xD;
          -  Able to swallow oral medications&#xD;
&#xD;
        Additional Inclusion Criteria for GBM cohort&#xD;
&#xD;
          -  Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent&#xD;
             following radiation therapy and temozolomide according to the Response Assessment in&#xD;
             Neuro-Oncology (RANO) criteria&#xD;
&#xD;
          -  Must have archival tumor tissue available from a previous surgery for glioblastoma&#xD;
&#xD;
          -  Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by&#xD;
             MRI imaging within 21 days of starting treatment&#xD;
&#xD;
          -  Must be able to undergo MRI of the brain with gadolinium. Patients must be maintained&#xD;
             on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days)&#xD;
             prior to this baseline MRI&#xD;
&#xD;
          -  Must have recovered from prior therapy to grade ≤1 severity (except for alopecia and&#xD;
             lymphocytopenia) National Cancer Institute Common Terminology Criteria for Adverse&#xD;
             Events (NCI-CTCAE)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of untreated brain metastasis or history of leptomeningeal disease or&#xD;
             spinal cord compression&#xD;
&#xD;
          -  Has failed to recover from the reversible effects of prior anticancer therapy (does&#xD;
             not apply to GBM cohort)&#xD;
&#xD;
          -  Has uncontrolled or poorly controlled hypertension&#xD;
&#xD;
          -  Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease&#xD;
&#xD;
          -  Has had any major cardiovascular event within 6 months prior to study drug&#xD;
             administration&#xD;
&#xD;
          -  Has any other clinically significant cardiac, respiratory, or other medical or&#xD;
             psychiatric condition that might interfere with participation in the trial or&#xD;
             interfere with the interpretation of trial results&#xD;
&#xD;
          -  Has had major surgery within 4 weeks before first study drug administration&#xD;
&#xD;
          -  Has known HIV&#xD;
&#xD;
          -  Has an active infection requiring systemic treatment&#xD;
&#xD;
          -  Is participating in another therapeutic clinical trial&#xD;
&#xD;
        Additional Excusion Criteria for GBM cohort:&#xD;
&#xD;
          -  Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be&#xD;
             bevacizumab naïve)&#xD;
&#xD;
          -  Is receiving enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on&#xD;
             non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs.&#xD;
             Patients previously treated with EIAED may be enrolled if they have been off the EIAED&#xD;
             for 10 days or more prior to the first dose of belzutifan&#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>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trials Information</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 25, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <last_update_submitted>September 16, 2022</last_update_submitted>
  <last_update_submitted_qc>September 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Adenocarcinoma, Clear 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/NCT02974738
org study id: 6482-001
secondary id: PT2977-101
secondary id: MK-6482-001
nct id: NCT02974738
lead sponsor: 
has dmc: No
The primary objective of this study is to identify the maximum tolerated dose (MTD) of
      belzutifan Tablets and/or the recommended Phase 2 dose (RP2D) of belzutifan Tablets in
      patients with advanced solid tumors
Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of belzutifan Tablets, where
      patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient
      safety will be monitored with frequent physical examinations, vital sign measurements,
      electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording
      all adverse events (AEs). Blood will be obtained for analysis of the concentration of
      belzutifan and to assess biomarkers.

      Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 50 patients with
      advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.

      Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid
      tumors may be enrolled. Up to 3 different tumor types may be included in this part of the
      study.

      Part 2A: A cohort of 25 patients with glioblastoma (GBM)
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: maximum tolerated dose (MTD)
time frame: 3 Weeks
description: 21-Day Dose Limiting Toxicity Observation Period per Dose Group
arm group label: Part 1A
arm group type: Experimental
description: Drug: PART 1A: Belzutifan for the treatment of advanced solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of solid tumors.
arm group label: Part 1B
arm group type: Experimental
description: Drug: PART 1B: Belzutifan for the treatment of advanced ccRCC
Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC.
arm group label: Part 2
arm group type: Experimental
description: Drug: Part 2: Belzutifan for the treatment of other specified solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.
arm group label: Part 2A
arm group type: Experimental
description: Drug: Part 2A: Belzutifan for the treatment of patients with recurrent GBM who have been previously treated with radiation therapy and temozolomide
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.
intervention type: Drug
intervention name: Belzutifan
description: Belzutifan is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
arm group label: Part 1A
arm group label: Part 1B
arm group label: Part 2
arm group label: Part 2A
other name: PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482
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
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trials Information
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Adenocarcinoma
mesh term: Glioblastoma
mesh term: Carcinoma, Renal Cell
mesh term: Adenocarcinoma, Clear 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