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| ID | Type | Description | Link |
|---|---|---|---|
| PT2977-202 | Other Identifier | Peloton Study ID | |
| MK-6482-004 | Other Identifier | MSD | |
| 2023-509119-99-00 | Registry Identifier | EU CT | |
| U1111-1309-6063 | Registry Identifier | UTN | |
| 2018-000125-30 | EudraCT Number |
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This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belzutifan | Drug | 120 mg once daily (three 40 mg oral tablets once daily). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to approximately 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39284337 | Result | 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. | |
| 40228516 |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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Phase 2 Open Label
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| 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). | 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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. | Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose. |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| University of Pennsylvania Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15232 | United States |
| Vanderbilt Medical Center | Nashville | Tennessee | 37232 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| Aarhus University Hospital | Aarhus | Denmark |
| Hospital Georges Pompidou | Paris | France |
| Cambridge University Hospital | Cambridge | United Kingdom |
| Derived |
| 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. |
| 34818478 | Derived | 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. |
| Plain Language Summary | View source |
| ID | Term |
|---|---|
| D006623 | von Hippel-Lindau Disease |
| ID | Term |
|---|---|
| D020752 | Neurocutaneous Syndromes |
| D009422 | Nervous System Diseases |
| D000798 | Angiomatosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000072661 | Ciliopathies |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
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| ID | Term |
|---|---|
| C000720612 | belzutifan |
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