NCT03401788 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-04-13

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Belzutifan
label
Open Label Belzutifan
type
EXPERIMENTAL

interventions

arm Group Labels
Open Label Belzutifan
description
120 mg once daily (three 40 mg oral tablets once daily).
name
Belzutifan
other Names
PT2977
MK-6482
WELIREG™
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

intervention Model Description

Phase 2 Open Label

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 50
type: ESTIMATED

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors
time Frame
Up to approximately 4 years

secondary Outcomes

description
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.
measure
Duration of Response (DOR) in VHL Disease-Associated RCC Tumors
time Frame
Up to approximately 4 years
description
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).
measure
Time to Response (TTR) in VHL Disease-Associated RCC Tumors
time Frame
Up to approximately 4 years
description
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.
measure
Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors
time Frame
Up to approximately 4 years
description
TTS was defined as the interval from the start of study treatment to the date of surgery.
measure
Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors
time Frame
Up to approximately 4 years
description
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.
measure
ORR in VHL Disease-Associated Non-RCC Tumors
time Frame
Up to approximately 4 years
description
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.
measure
DOR in VHL Disease-Associated Non-RCC Tumors
time Frame
Up to approximately 4 years
description
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).
measure
TTR in VHL Disease-Associated Non-RCC Tumors
time Frame
Up to approximately 4 years
description
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.
measure
PFS in VHL Disease-Associated Non-RCC Tumors
time Frame
Up to approximately 4 years
description
TTS was defined as the interval from the start of study treatment to the date of surgery.
measure
TTS in VHL Disease-Associated Non-RCC Tumors
time Frame
Up to approximately 4 years
description
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.
measure
Number of Participants Experiencing an Adverse Event (AE)
time Frame
Up to approximately 4 years
description
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.
measure
Number of Participants Experiencing a Serious Adverse Event (SAE)
time Frame
Up to approximately 4 years
description
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
measure
Belzutifan Plasma Concentration
time Frame
Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.

Full study description

brief Summary: This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.
detailed Description: 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.

Source references

references

citation
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.
pmid
39284337
type
RESULT
citation
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.
pmid
40228516
type
DERIVED
citation
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.
pmid
34818478
type
DERIVED