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)

VHL Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03401788
• Other study ID #: 6482-004
• Secondary ID: PT2977-202MK-648
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2, 2018
• Est. completion date: March 29, 2026

Study information

• Verified date: February 2024
• Source: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 29, 2026
• Est. primary completion date: March 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-2a 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Syndrome
• VHL - Von Hippel-Lindau Syndrome
• VHL Gene Inactivation
• VHL Gene Mutation
• VHL Syndrome
• VHL-Associated Clear Cell Renal Cell Carcinoma
• VHL-Associated Renal Cell Carcinoma
• Von Hippel-Lindau Disease

Intervention

Drug:
• Belzutifan
120 mg once daily (three 40 mg oral tablets once daily).

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
France	Hospital Georges Pompidou	Paris
United Kingdom	Cambridge University Hospital	Cambridge
United States	University of Michigan	Ann Arbor	Michigan
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Denmark,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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.	Up to approximately 4 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.

External Links

•   Merck Clinical Trials Information