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

NCT02974738 | Active Not Recruiting Phase 1

• 3 other identifiers: 6482-001PT2977-101MK-6482-001
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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

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

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  21-Day Dose Limiting Toxicity Observation Period per Dose Group

  3 Weeks

Study Arms (4)

Part 1A

EXPERIMENTAL

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

Part 1B

EXPERIMENTAL

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

Part 2

EXPERIMENTAL

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

Part 2A

EXPERIMENTAL

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

Interventions

Belzutifan DRUG

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

Also known as: PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482, WELIREG™

Part 1A; Part 1B; Part 2; Part 2A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Related Publications (2)

• Jonasch E, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Dror Michaelson M, Appleman LJ, Roy A, Perini RF, Liu Y, Choueiri TK. Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort. Eur J Cancer. 2024 Jan;196:113434. doi: 10.1016/j.ejca.2023.113434. Epub 2023 Nov 15.

  PMID: 38008031 DERIVED

• 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.

  PMID: 33888901 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasm Metastasis; Glioblastoma

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2016
• First Posted: November 28, 2016
• Study Start: December 7, 2016
• Primary Completion: January 12, 2018
• Study Completion (Estimated): April 14, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share