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

• ClinicalTrials.gov Identifier: NCT02974738
• Recruitment Status: Active, not recruiting
• First Posted: November 28, 2016
• Last Update Posted: September 19, 2022
• Sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• Information provided by (Responsible Party): Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Tracking Information

• First Submitted Date: November 23, 2016
• First Posted Date: November 28, 2016
• Last Update Posted Date: September 19, 2022
• Actual Study Start Date: December 7, 2016
• Actual Primary Completion Date: January 12, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)
• Official Title: A Phase 1, 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

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:

• PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482
• WELIREG™

Study Arms

• 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-2alpha 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. Erratum In: Nat Med. 2021 Oct;27(10):1849.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 14, 2022): 120
• Original Estimated Enrollment (submitted: November 25, 2016): 125
• Estimated Study Completion Date: April 14, 2025
• Actual Primary Completion Date: January 12, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT02974738
• Other Study ID Numbers: 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

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• Original Responsible Party: Same as current
• Current Study Sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• Verification Date: September 2022