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CompletedNCT03108066Updated Sep 24, 2024Results posted

MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)

A Phase 2 interventional study of MK-3795 in VHL Gene Mutation, VHL and VHL Syndrome, sponsored by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-24.

Sponsored by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The primary objective of this study is to assess the overall response rate (ORR) of von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC) tumors in VHL participants treated with MK-3795.

Read the detailed description

This open-label Phase 2 study will evaluate the efficacy, safety, PK, and PD of MK-3795 in participants with VHL disease who have at least 1 measurable VHL disease-associated ccRCC tumor (as defined by RECIST 1.1). MK-3795 will be administered orally and treatment will be continuous. Changes in VHL disease-associated non-ccRCC tumors will also be evaluated.

02

Conditions studied

  • VHL Gene Mutation
  • VHL
  • VHL Syndrome
  • VHL Gene Inactivation
  • Von Hippel
  • Von Hippel-Lindau Disease
  • Von Hippel's Disease
  • Von Hippel-Lindau Syndrome, Modifiers of
  • Clear Cell Renal Cell Carcinoma
  • Clear Cell RCC
  • ccRCC
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.

This study's enrollment of 4 is below the median of 45 across 5,174 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) is the lead sponsor of 7 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Has at least 1 measurable ccRCC tumor and no solid ccRCC tumor greater than 3.0 cm, based on radiologic diagnosis (histologic diagnosis not required); may have VHL disease-associated lesions in other organ systems
  • Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration

Exclusion criteria

Exclusion Criteria:

  • Has had prior radiotherapy or systemic anti cancer therapy for ccRCC (includes anti-vascular endothelial growth factor (VEGF) therapy or any systemic investigational anti cancer agent)
  • Has a prior or concomitant non-VHL disease-associated invasive malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the participant has remained disease free for more than 2 years
  • Has any history of metastatic disease
  • Has had radiotherapy to any non-ccRCC site within 4 weeks prior to entering the study or has not recovered from adverse events (AE)
  • Has had any surgical procedure for VHL disease or any major surgical procedure completed within 4 weeks prior to entering the study or has any surgical lesions from recent major surgical procedures that are not well healed
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    MK-3795

    Participants receive 800 mg MK-3795 orally twice daily. Participants may continue to receive MK-3795 in the absence of unacceptable treatment related toxicity or unequivocal disease progression.

    Drug: MK-3795

Interventions

  • DrugMK-3795

    800 mg twice daily (four 200 mg oral tablets twice daily)

    Also known as: PT2385, PT-2385

06

What researchers measure

Primary outcomes

  1. Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors

    ORR was 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 was assessed by independent review committee (ICR) for the primary analysis.

    Time frame: Up to approximately 76 months

Secondary outcomes

  1. Progression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors

    PFS was defined as the interval from the start of study treatment to the first documented Progressive Disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD was 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 was also considered PD.

    Time frame: Up to approximately 76 months

  2. Duration of Response (DOR) in VHL Disease-Associated ccRCC Tumors

    DOR was 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 was 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 was also considered PD.

    Time frame: Up to approximately 76 months

  3. Time to Response (TTR) in VHL Disease-Associated ccRCC Tumors

    TTR was 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 76 months

  4. Overall Response Rate (ORR) in VHL Disease-Associated Non-ccRCC Tumors

    ORR was 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).

    Time frame: Up to approximately 76 months

  5. Progression-free Survival (PFS) in VHL Disease-Associated Non-ccRCC Tumors

    PFS was 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 was also considered PD.

    Time frame: Up to approximately 76 months

  6. Duration of Response (DOR) in VHL Disease-Associated Non-ccRCC Tumors

    DOR was 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 was 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 was also considered PD.

    Time frame: Up to approximately 76 months

  7. Time to Response (TTR) in VHL Disease-Associated Non-ccRCC Tumors

    TTR was 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 76 months

  8. MK-3795 Plasma Concentration

    Blood samples for the determination of MK-3795 concentration were collected at pre-specified timepoints before and after administration of study intervention.

    Time frame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose

  9. MK-3795 Metabolite Plasma Concentration

    Blood samples for the determination of MK-3795 metabolite concentration were collected at pre-specified timepoints before and after administration of study intervention.

    Time frame: Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose

  10. Number of Participants Who Experienced One or More Adverse Events (AEs)

    An AE was defined as 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 was considered to be study drug related.

    Time frame: Up to approximately 76 months

  11. Number of Participants Who Discontinued Study Intervention Due to an AE

    An AE was defined as 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 74 months

07

Results

Posted Sep 24, 2024

Participant flow

Participant flow — Overall Study
MilestoneMK-3795
Started4
Completed4
Not completed0

Outcome measures

PrimaryOverall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors

ORR was 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 was assessed by independent review committee (ICR) for the primary analysis.

Time frame:
Up to approximately 76 months
Reported as:
Number · Percentage of Participants
Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors
Percentage of ParticipantsMK-3795
Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors0.0 (0.0 to 60.2)
SecondaryProgression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors

PFS was defined as the interval from the start of study treatment to the first documented Progressive Disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD was 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 was also considered PD.

Time frame:
Up to approximately 76 months
Reported as:
Median · Months
Progression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors
MonthsMK-3795
Progression-free Survival (PFS) in VHL Disease-Associated ccRCC TumorsNA (NA to NA)
SecondaryDuration of Response (DOR) in VHL Disease-Associated ccRCC Tumors

DOR was 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 was 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 was also considered PD.

Time frame:
Up to approximately 76 months

No measurements were reported for this outcome.

SecondaryTime to Response (TTR) in VHL Disease-Associated ccRCC Tumors

TTR was 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 76 months

No measurements were reported for this outcome.

SecondaryOverall Response Rate (ORR) in VHL Disease-Associated Non-ccRCC Tumors

ORR was 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).

Time frame:
Up to approximately 76 months

No measurements were reported for this outcome.

SecondaryProgression-free Survival (PFS) in VHL Disease-Associated Non-ccRCC Tumors

PFS was 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 was also considered PD.

Time frame:
Up to approximately 76 months

No measurements were reported for this outcome.

SecondaryDuration of Response (DOR) in VHL Disease-Associated Non-ccRCC Tumors

DOR was 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 was 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 was also considered PD.

Time frame:
Up to approximately 76 months

No measurements were reported for this outcome.

SecondaryTime to Response (TTR) in VHL Disease-Associated Non-ccRCC Tumors

TTR was 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 76 months

No measurements were reported for this outcome.

SecondaryMK-3795 Plasma Concentration

Blood samples for the determination of MK-3795 concentration were collected at pre-specified timepoints before and after administration of study intervention.

Time frame:
Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose
Reported as:
Geometric mean · ng/mL
MK-3795 Plasma Concentration
ng/mLMK-3795
Week 1 Pre-doseNA ± NA
Week 1 6 Hours Post-dose583 ± 104.6
Week 3 Pre-dose1750 ± 76.8
Week 5 Pre-dose1480 ± 93.5
Week 9 Pre-dose2550 ± NA
Week 13 Pre-dose3150 ± NA
SecondaryMK-3795 Metabolite Plasma Concentration

Blood samples for the determination of MK-3795 metabolite concentration were collected at pre-specified timepoints before and after administration of study intervention.

Time frame:
Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose
Reported as:
Geometric mean · ng/mL
MK-3795 Metabolite Plasma Concentration
ng/mLMK-3795
Week 1 Pre-doseNA ± NA
Week 1 6 Hours Post-dose2790 ± 95.5
Week 3 Pre-dose4530 ± 53.7
Week 5 Pre-dose3440 ± 62.9
Week 9 Pre-dose5790 ± NA
Week 13 Pre-dose6360 ± NA
SecondaryNumber of Participants Who Experienced One or More Adverse Events (AEs)

An AE was defined as 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 was considered to be study drug related.

Time frame:
Up to approximately 76 months
Reported as:
Count of participants · Participants
Number of Participants Who Experienced One or More Adverse Events (AEs)
ParticipantsMK-3795
Number of Participants Who Experienced One or More Adverse Events (AEs)4
SecondaryNumber of Participants Who Discontinued Study Intervention Due to an AE

An AE was defined as 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 74 months
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Study Intervention Due to an AE
ParticipantsMK-3795
Number of Participants Who Discontinued Study Intervention Due to an AE2

Adverse events

Collected over Up to approximately 76 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-37950/4 (0%)3/4 (75%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventMK-3795
AphasiaNervous system disorders3/4
Most frequent other events
Showing 10 of 56
Most frequent other events
EventMK-3795
NauseaGastrointestinal disorders4/4
Dry eyeEye disorders3/4
FatigueGeneral disorders3/4
AphasiaNervous system disorders3/4
BradycardiaCardiac disorders2/4
Vision blurredEye disorders2/4
HyperglycaemiaMetabolism and nutrition disorders2/4
ArthralgiaMusculoskeletal and connective tissue disorders2/4
Neck painMusculoskeletal and connective tissue disorders2/4
Pain in extremityMusculoskeletal and connective tissue disorders2/4

Baseline characteristics

Age, Continuous
Age, Continuous(Years)MK-3795
Mean58.3 ± 8.14
Sex: Female, Male
Sex: Female, Male(Participants)MK-3795
Female4
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)MK-3795
Hispanic or Latino0
Not Hispanic or Latino4
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)MK-3795
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White4
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Larcher A, Rowe I, Belladelli F, Fallara G, Raggi D, Necchi A, Montorsi F, Capitanio U, Salonia A; OSR VHL Program. Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950. PubMed 34783716 ↗

Study documents

  • Protocol and statistical analysis plan · Jul 25, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 24, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03108066
Lead sponsor
Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Collaborators
National Institutes of Health (NIH)
Responsible party
Sponsor
First posted
Apr 11, 2017
Start date
Apr 24, 2017
Primary completion
Aug 30, 2023
Completion
Sep 27, 2023
Results posted
Sep 24, 2024
Last update
Sep 24, 2024

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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