Clinical trial 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)
Official title: An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 2 Open Label
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Duration of Response (DOR) in VHL Disease-Associated RCC Tumors
timeFrame: Up to approximately 4 years
measure: Time to Response (TTR) in VHL Disease-Associated RCC Tumors
timeFrame: Up to approximately 4 years
measure: Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors
timeFrame: Up to approximately 4 years
measure: Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors
timeFrame: Up to approximately 4 years
measure: ORR in VHL Disease-Associated Non-RCC Tumors
timeFrame: Up to approximately 4 years
measure: DOR in VHL Disease-Associated Non-RCC Tumors
timeFrame: Up to approximately 4 years
measure: TTR in VHL Disease-Associated Non-RCC Tumors
timeFrame: Up to approximately 4 years
measure: PFS in VHL Disease-Associated Non-RCC Tumors
timeFrame: Up to approximately 4 years
measure: TTS in VHL Disease-Associated Non-RCC Tumors
timeFrame: Up to approximately 4 years
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to approximately 4 years
measure: Number of Participants Experiencing a Serious Adverse Event (SAE)
timeFrame: Up to approximately 4 years
measure: Belzutifan Plasma Concentration
timeFrame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
measure: Belzutifan Metabolite Plasma Concentration
timeFrame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Paris
country: France
facility: Hospital Georges Pompidou
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
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.
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.