VHL - Von Hippel-Lindau SyndromePhase 2NCT03401788
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)
A Phase 2 study testing Belzutifan in people with VHL - Von Hippel-Lindau Syndrome and VHL Gene Mutation, run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 11 sites in 4 countries.
Trial summary
This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- VHL - Von Hippel-Lindau Syndrome, VHL Gene Mutation, VHL Syndrome
- What is being tested?
- Belzutifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 2 May 2018to 29 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States8 sites
University of Michigan
Ann Arbor, Michigan, 48109
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Massachusetts General Hospital
Boston, Massachusetts, 02114
MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt Medical Center
Nashville, Tennessee, 37232
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma
This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.
Read the 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.
- Conditions
- 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
- Being tested
- Belzutifan
- Keywords
- VHL
- Medical subject headings
- von Hippel-Lindau Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Also called PT2977, MK-6482, WELIREG™
120 mg once daily (three 40 mg oral tablets once daily).
| Study group | Role | What they receive |
|---|---|---|
| Open Label Belzutifan | Experimental | 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. Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors
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.
Measured: Up to approximately 4 years
Secondary outcomes (13)
Duration of Response (DOR) in VHL Disease-Associated RCC Tumors
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.
Measured: Up to approximately 4 years
Time to Response (TTR) in VHL Disease-Associated RCC Tumors
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).
Measured: Up to approximately 4 years
Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors
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.
Measured: Up to approximately 4 years
Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors
TTS was defined as the interval from the start of study treatment to the date of surgery.
Measured: Up to approximately 4 years
ORR in VHL Disease-Associated Non-RCC Tumors
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.
Measured: Up to approximately 4 years
DOR in VHL Disease-Associated Non-RCC Tumors
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.
Measured: Up to approximately 4 years
TTR in VHL Disease-Associated Non-RCC Tumors
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).
Measured: Up to approximately 4 years
PFS in VHL Disease-Associated Non-RCC Tumors
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.
Measured: Up to approximately 4 years
TTS in VHL Disease-Associated Non-RCC Tumors
TTS was defined as the interval from the start of study treatment to the date of surgery.
Measured: Up to approximately 4 years
Number of Participants Experiencing an Adverse Event (AE)
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.
Measured: Up to approximately 4 years
Number of Participants Experiencing a Serious Adverse Event (SAE)
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.
Measured: Up to approximately 4 years
Belzutifan Plasma Concentration
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
Measured: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
Belzutifan Metabolite Plasma Concentration
Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.
Measured: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start2 May 2018
- Primary completion29 Apr 2027 (estimated)
- Study completion29 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for VHL - Von Hippel-Lindau SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 2 Open Label
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401788
- Sponsor's protocol ID
- 6482-004
- Other IDs
- PT2977-202, MK-6482-004, 2023-509119-99-00, U1111-1309-6063, 2018-000125-30, 2018, 2023
- Status last verified
- Apr 2026
- First submitted
- 9 Jan 2018
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 39284337Srinivasan 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.
PubMed 40228516Jonasch 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.
PubMed 34818478
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03401788
- Acronym / sponsor ID
- 6482-004
- Conditions
- 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
- Keywords
- VHL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 2 May 2018 (actual)
- Primary completion
- 29 Apr 2027 (estimated)
- Study completion
- 29 Apr 2027 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 2 Open Label
| Arm | Type | Receives |
|---|---|---|
| Open Label Belzutifan | Experimental | Drug: BelzutifanParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelzutifanAlso: PT2977, MK-6482, WELIREG™120 mg once daily (three 40 mg oral tablets once daily). | Drug | Open Label Belzutifan |
Primary outcome
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.
13 secondary outcomes
Duration of Response (DOR) in VHL Disease-Associated RCC Tumors
Time frame: Up to approximately 4 years
Time to Response (TTR) in VHL Disease-Associated RCC Tumors
Time frame: Up to approximately 4 years
Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors
Time frame: Up to approximately 4 years
Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors
Time frame: Up to approximately 4 years
ORR in VHL Disease-Associated Non-RCC Tumors
Time frame: Up to approximately 4 years
DOR in VHL Disease-Associated Non-RCC Tumors
Time frame: Up to approximately 4 years
TTR in VHL Disease-Associated Non-RCC Tumors
Time frame: Up to approximately 4 years
PFS in VHL Disease-Associated Non-RCC Tumors
Time frame: Up to approximately 4 years
TTS in VHL Disease-Associated Non-RCC Tumors
Time frame: Up to approximately 4 years
Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to approximately 4 years
Number of Participants Experiencing a Serious Adverse Event (SAE)
Time frame: Up to approximately 4 years
Belzutifan Plasma Concentration
Time frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Results publication: PubMed 39284337Iliopoulos 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.
- Derived from this study: PubMed 40228516Srinivasan 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.
- Derived from this study: PubMed 34818478Jonasch 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.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belzutifan in people with VHL - Von Hippel-Lindau Syndrome and VHL Gene Mutation, run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Denmark, France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors (time frame: Up to approximately 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03401788, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.