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OpenTrials
Active, Not Recruiting

NCT Number: NCT03401788

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)

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

VHL - Von Hippel-Lindau Syndrome Abnormalities, Multiple Angiomatosis Cardiovascular Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Nervous System Diseases Neurocutaneous Syndromes VHL Gene Inactivation VHL Gene Mutation VHL Syndrome VHL-Associated Clear Cell Renal Cell Carcinoma VHL-Associated Renal Cell Carcinoma Vascular Diseases von Hippel-Lindau Disease

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aarhus University Hospital, Aarhus, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Belzutifan

Drug

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

Other names: PT2977, MK-6482, WELIREG™

Primary outcomes

  1. Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors

    Time frame: Up to approximately 4 years

    ORR is defined as the percentage of participants in the analysis population who have a best confirmed response of Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by independent review committee (ICR) for the primary analysis.

Secondary outcomes

  1. Duration of Response (DOR) in VHL Disease-Associated RCC Tumors

    Time frame: Up to approximately 4 years

    DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  2. Time to Response (TTR) in VHL Disease-Associated RCC Tumors

    Time frame: Up to approximately 4 years

    TTR is defined as the interval from the start of study treatment to the first documentation of a response per RECIST 1.1, and calculated for participants with a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions).

  3. Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors

    Time frame: Up to approximately 4 years

    PFS is defined as the interval from the start of study treatment to the first documented PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  4. Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors

    Time frame: Up to approximately 4 years

    TTS was defined as the interval from the start of study treatment to the date of surgery.

  5. ORR in VHL Disease-Associated Non-RCC Tumors

    Time frame: Up to approximately 4 years

    ORR is defined as the percentage of participants in the analysis population who have a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1.

  6. DOR in VHL Disease-Associated Non-RCC Tumors

    Time frame: Up to approximately 4 years

    DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until PD or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  7. TTR in VHL Disease-Associated Non-RCC Tumors

    Time frame: Up to approximately 4 years

    TTR is defined as the interval from the start of study treatment to the first documentation of a response per RECIST 1.1, and calculated for participants with a best confirmed response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions).

  8. PFS in VHL Disease-Associated Non-RCC Tumors

    Time frame: Up to approximately 4 years

    PFS is defined as the interval from the start of study treatment to the first documented PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  9. TTS in VHL Disease-Associated Non-RCC Tumors

    Time frame: Up to approximately 4 years

    TTS was defined as the interval from the start of study treatment to the date of surgery.

  10. Number of Participants Experiencing an Adverse Event (AE)

    Time frame: Up to approximately 4 years

    An AE is any untoward medical occurrence in a participant regardless of its causal relationship to study treatment. An AE can be any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug, whether or not it is considered to be study drug related.

  11. Number of Participants Experiencing a Serious Adverse Event (SAE)

    Time frame: Up to approximately 4 years

    An SAE is any AE occurring at any dose and regardless of causality that meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly or birth defect in an offspring of a participant taking study drug, or is an important medical event.

  12. Belzutifan Plasma Concentration

    Time frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.

    Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.

  13. Belzutifan Metabolite Plasma Concentration

    Time frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.

    Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.

Sponsors and collaborators

Lead sponsor

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

Industry

Registry information

Official study title

An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma

Important dates

Study start
2018
Primary completion
2027
Study completion
2027
First posted
Jan 17, 2018
Registry last updated
Apr 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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