search
Back to results

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)

Primary Purpose

VHL - Von Hippel-Lindau Syndrome, VHL Gene Mutation, VHL Syndrome

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Belzutifan
Sponsored by
Peloton Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for VHL - Von Hippel-Lindau Syndrome focused on measuring VHL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • National Institutes of Health Clinical Center
  • Massachusetts General Hospital
  • University of Michigan
  • University of Pennsylvania Medical Center
  • University of Pittsburgh Medical Center
  • Vanderbilt Medical Center
  • MD Anderson Cancer Center
  • Huntsman Cancer Institute
  • Aarhus University Hospital
  • Hospital Georges Pompidou
  • Cambridge University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label Belzutifan

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.
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).
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.
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.
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.
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.
Belzutifan Plasma Concentration
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
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.

Full Information

First Posted
January 9, 2018
Last Updated
November 1, 2022
Sponsor
Peloton Therapeutics, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03401788
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2, 2018 (Actual)
Primary Completion Date
March 29, 2026 (Anticipated)
Study Completion Date
March 29, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peloton Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 2 Open Label
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open Label Belzutifan
Arm Type
Experimental
Arm 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 Type
Drug
Intervention Name(s)
Belzutifan
Other Intervention Name(s)
PT2977, MK-6482, WELIREG™
Intervention Description
120 mg once daily (three 40 mg oral tablets once daily).
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors
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.
Time Frame
Up to approximately 4 years
Secondary Outcome Measure Information:
Title
Duration of Response (DOR) in VHL Disease-Associated RCC Tumors
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.
Time Frame
Up to approximately 4 years
Title
Time to Response (TTR) in VHL Disease-Associated RCC Tumors
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).
Time Frame
Up to approximately 4 years
Title
Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors
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.
Time Frame
Up to approximately 4 years
Title
Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors
Description
TTS was defined as the interval from the start of study treatment to the date of surgery.
Time Frame
Up to approximately 4 years
Title
ORR in VHL Disease-Associated Non-RCC Tumors
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.
Time Frame
Up to approximately 4 years
Title
DOR in VHL Disease-Associated Non-RCC Tumors
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.
Time Frame
Up to approximately 4 years
Title
TTR in VHL Disease-Associated Non-RCC Tumors
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).
Time Frame
Up to approximately 4 years
Title
PFS in VHL Disease-Associated Non-RCC Tumors
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.
Time Frame
Up to approximately 4 years
Title
TTS in VHL Disease-Associated Non-RCC Tumors
Description
TTS was defined as the interval from the start of study treatment to the date of surgery.
Time Frame
Up to approximately 4 years
Title
Number of Participants Experiencing an Adverse Event (AE)
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.
Time Frame
Up to approximately 4 years
Title
Number of Participants Experiencing a Serious Adverse Event (SAE)
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.
Time Frame
Up to approximately 4 years
Title
Belzutifan Plasma Concentration
Description
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
Time Frame
Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.
Title
Belzutifan Metabolite Plasma Concentration
Description
Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.
Time Frame
Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Pennsylvania Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Facility Name
Hospital Georges Pompidou
City
Paris
Country
France
Facility Name
Cambridge University Hospital
City
Cambridge
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34818478
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.
Results Reference
derived
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

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)

We'll reach out to this number within 24 hrs