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

September 16, 2022 updated by: Peloton Therapeutics, Inc.

A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

120

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • WELIREG™
  • 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 Names:
  • WELIREG™
  • 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 Names:
  • WELIREG™
  • 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 Names:
  • WELIREG™
  • PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
maximum tolerated dose (MTD)
Time Frame: 3 Weeks
21-Day Dose Limiting Toxicity Observation Period per Dose Group
3 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peloton Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2016

Primary Completion (Actual)

January 12, 2018

Study Completion (Anticipated)

April 14, 2025

Study Registration Dates

First Submitted

November 23, 2016

First Submitted That Met QC Criteria

November 25, 2016

First Posted (Estimate)

November 28, 2016

Study Record Updates

Last Update Posted (Actual)

September 19, 2022

Last Update Submitted That Met QC Criteria

September 16, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-001
  • PT2977-101 (Other Identifier: Pelaton Study ID)
  • MK-6482-001 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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