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A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)

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ClinicalTrials.gov Identifier: NCT02974738
Recruitment Status : Active, not recruiting
First Posted : November 28, 2016
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
Peloton Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE November 23, 2016
First Posted Date  ICMJE November 28, 2016
Last Update Posted Date February 26, 2021
Actual Study Start Date  ICMJE December 7, 2016
Estimated Primary Completion Date April 14, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2016)
maximum tolerated dose (MTD) [ Time Frame: 3 Weeks ]
21-Day Dose Limiting Toxicity Observation Period per Dose Group
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)
Official Title  ICMJE A Phase 1, Multiple-Dose, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
Brief Summary 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
Detailed Description

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)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Solid Tumor
  • Solid Carcinoma
  • Solid Tumor, Adult
  • ccRCC
  • RCC, Clear Cell Adenocarcinoma
  • RCC
  • Kidney Cancer
  • Clear Cell Renal Cell Carcinoma
  • Renal Cell Carcinoma, Metastatic
  • Renal Cell Carcinoma Recurrent
  • Renal Cell Carcinoma, Clear Cell Adenocarcinoma
  • Glioblastoma
  • Glioblastoma, Adult
  • GBM
  • Glioblastoma Multiforme
Intervention  ICMJE Drug: Belzutifan
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
Other Name: PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482
Study Arms  ICMJE
  • Experimental: Part 1A

    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.

    Intervention: Drug: Belzutifan
  • Experimental: Part 1B

    Drug: PART 1B: Belzutifan for the treatment of advanced ccRCC

    Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC.

    Intervention: Drug: Belzutifan
  • Experimental: Part 2

    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.

    Intervention: Drug: Belzutifan
  • Experimental: Part 2A

    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: Drug: Belzutifan
Publications * Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021 May;27(5):802-805. doi: 10.1038/s41591-021-01324-7. Epub 2021 Apr 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 5, 2020)
123
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2016)
125
Estimated Study Completion Date  ICMJE April 14, 2023
Estimated Primary Completion Date April 14, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a diagnosis of locally advanced or metastatic solid tumor
  • Is of age ≥ 18 years
  • Has a life expectancy of ≥ 6 months
  • Has adequate organ function
  • If a female patient, must not be pregnant or breastfeeding and not a woman of childbearing potential (WOCBP) OR a WOCBP who uses contraception or is abstinent from heterosexual intercourse during the study and for a minimum of 30 days after the last study drug administration, or if a male patient, must be abstinent from heterosexual intercourse OR agree to use contraception
  • Able to swallow oral medications

Additional Inclusion Criteria for GBM cohort

  • Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria
  • Must have archival tumor tissue available from a previous surgery for glioblastoma
  • Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by MRI imaging within 21 days of starting treatment
  • Must be able to undergo MRI of the brain with gadolinium. Patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
  • Must have recovered from prior therapy to grade ≤1 severity (except for alopecia and lymphocytopenia) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Exclusion Criteria:

  • Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression
  • Has failed to recover from the reversible effects of prior anticancer therapy (does not apply to GBM cohort)
  • Has uncontrolled or poorly controlled hypertension
  • Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease
  • Has had any major cardiovascular event within 6 months prior to study drug administration
  • Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
  • Has had major surgery within 4 weeks before first study drug administration
  • Has known HIV
  • Has an active infection requiring systemic treatment
  • Is participating in another therapeutic clinical trial

Additional Excusion Criteria for GBM cohort:

  • Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naïve)
  • Is receiving enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of belzutifan
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02974738
Other Study ID Numbers  ICMJE 6482-001
PT2977-101 ( Other Identifier: Pelaton Study ID )
MK-6482-001 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Peloton Therapeutics, Inc.
Study Sponsor  ICMJE Peloton Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Peloton Therapeutics, Inc.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP