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)

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 frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Weeks 1 and 3: pre-dose, 2 and 5 hours post-dose, Week 5, 9, and 13: post-dose.