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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.

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

Condition or disease Intervention/treatment Phase
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 Drug: Belzutifan Phase 1

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 123 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multiple-Dose, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
Actual Study Start Date : December 7, 2016
Estimated Primary Completion Date : April 14, 2023
Estimated Study Completion Date : April 14, 2023


Arm Intervention/treatment
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.

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

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.

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

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.

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

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.

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




Primary Outcome Measures :
  1. maximum tolerated dose (MTD) [ Time Frame: 3 Weeks ]
    21-Day Dose Limiting Toxicity Observation Period per Dose Group



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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 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
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Responsible Party: Peloton Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02974738    
Other Study ID Numbers: 6482-001
PT2977-101 ( Other Identifier: Pelaton Study ID )
MK-6482-001 ( Other Identifier: Merck )
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021
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
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Adenocarcinoma
Glioblastoma
Carcinoma, Renal Cell
Adenocarcinoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases