Clinical Trials /

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

NCT02974738

Description:

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

Related Conditions:
  • Glioblastoma
  • Glioblastoma, IDH-Wildtype
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, Multiple-Dose, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 6482-001
  • SECONDARY ID: PT2977-101
  • NCT ID: NCT02974738

Conditions

  • 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

Interventions

DrugSynonymsArms
BelzutifanPT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482Part 1A

Purpose

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)
    

Trial Arms

NameTypeDescriptionInterventions
Part 1AExperimentalDrug: PART 1A: Belzutifan for the treatment of advanced solid tumors Belzutifan inhibits HIF-2α and is a novel approach to treatment of solid tumors.
  • Belzutifan
Part 1BExperimentalDrug: PART 1B: Belzutifan for the treatment of advanced ccRCC Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC.
  • Belzutifan
Part 2ExperimentalDrug: 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.
  • Belzutifan
Part 2AExperimentalDrug: 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.
  • Belzutifan

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Peloton Therapeutics, Inc.

Last Updated

November 9, 2020