A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)

NCT ID: NCT03401788

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-02

Study Completion Date

2026-03-29

Brief Summary

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This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.

Detailed Description

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This open-label Phase 2 study will evaluate the efficacy and safety of belzutifan in participants with VHL disease who have at least 1 measurable RCC tumor. Belzutifan will be administered orally and treatment will be continuous. Participants will be evaluated radiologically approximately 12 weeks after initiation of treatment and every 12 weeks thereafter while continuing in the study for a minimum of 3 years and then every 24 weeks or more frequently if clinically indicated. Changes in VHL disease-associated non-RCC tumors will also be evaluated.

Conditions

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VHL - Von Hippel-Lindau Syndrome VHL Gene Mutation VHL Syndrome VHL Gene Inactivation VHL-Associated Renal Cell Carcinoma VHL-Associated Clear Cell Renal Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Phase 2 Open Label
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Open Label Belzutifan

Participants receive 120 mg belzutifan orally once daily. Participants may continue to receive belzutifan in the absence of unacceptable treatment related toxicity or unequivocal disease progression.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

120 mg once daily (three 40 mg oral tablets once daily).

Interventions

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Belzutifan

120 mg once daily (three 40 mg oral tablets once daily).

Intervention Type DRUG

Other Intervention Names

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PT2977 MK-6482 WELIREG™

Eligibility Criteria

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Inclusion Criteria

* Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration
* Has at least 1 measurable solid RCC tumor and no RCC tumor that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Participants may have VHL disease-associated tumors in other organ systems

Exclusion Criteria

* Has received prior treatment with belzutifan or another HIF-2α inhibitor
* Has had any systemic anti-cancer therapy (includes anti-vascular endothelial growth factor \[VEGF\] therapy or any systemic investigational anti-cancer agent)
* Has an immediate need for surgical intervention for tumor treatment
* Has evidence of metastatic disease on screening imaging
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Hospital Georges Pompidou

Paris, , France

Site Status

Cambridge University Hospital

Cambridge, , United Kingdom

Site Status

Countries

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United States Denmark France United Kingdom

References

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Iliopoulos O, Iversen AB, Narayan V, Maughan BL, Beckermann KE, Oudard S, Else T, Maranchie JK, Goldberg CM, Fu W, Perini RF, Liu Y, Linehan WM, Srinivasan R, Jonasch E. Belzutifan for patients with von Hippel-Lindau disease-associated CNS haemangioblastomas (LITESPARK-004): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2024 Oct;25(10):1325-1336. doi: 10.1016/S1470-2045(24)00389-9. Epub 2024 Sep 13.

Reference Type RESULT
PMID: 39284337 (View on PubMed)

Srinivasan R, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, Oudard S, Else T, Maranchie JK, Iversen AB, Cornell J, Perini RF, Liu Y, Linehan WM, Jonasch E. Belzutifan for von Hippel-Lindau disease-associated renal cell carcinoma and other neoplasms (LITESPARK-004): 50 months follow-up from a single-arm, phase 2 study. Lancet Oncol. 2025 May;26(5):571-582. doi: 10.1016/S1470-2045(25)00099-3. Epub 2025 Apr 12.

Reference Type DERIVED
PMID: 40228516 (View on PubMed)

Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425.

Reference Type DERIVED
PMID: 34818478 (View on PubMed)

Related Links

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Other Identifiers

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PT2977-202

Identifier Type: OTHER

Identifier Source: secondary_id

MK-6482-004

Identifier Type: OTHER

Identifier Source: secondary_id

2023-509119-99

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-000125-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

6482-004

Identifier Type: -

Identifier Source: org_study_id