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Von Hippel-Lindau Disease

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Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Twenty-five patients will be enrolled in each stage of a two-stage design

PT2385 inhibits HIF-2α and is a novel approach to treatment of VHL disease-associated ccRCC.

PT2385 Tablets

Medical Director

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 patients treated with PT2385.

This open-label Phase 2 study will evaluate the efficacy, safety, PK, and PD of PT2385 in patients with VHL disease who have at least 1 measurable VHL disease-associated ccRCC tumor (as defined by RECIST 1.1). PT2385 will be administered orally and treatment will be continuous. Changes in VHL disease-associated non-ccRCC tumors will also be evaluated.

This is an open-label Phase 2 study that will be conducted with a 2-stage design.

PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

An Open Label Phase 2 Study to Evaluate PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Overall response rate (ORR) in VHL disease-associated ccRCC tumors

Progression free survival (PFS) in VHL disease-associated ccRCC tumors

Duration of response (DOR) in VHL disease-associated ccRCC tumors

Time to response (TTR) in VHL disease-associated ccRCC tumors

An AE is defined as any untoward medical occurrence in a patient 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.

National Institutes of Health (NIH)

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

Antineoplastic Agents

All Drugs and Chemicals

Belzutifan

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.

120 mg once daily (three 40 mg oral tablets once daily).

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

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.

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)

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

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.

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.

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 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 was defined as the interval from the start of study treatment to the date of surgery.

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 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.

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.

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.

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma	NCT03108066	VHL Gene Mutati... VHL VHL Syndrome VHL Gene Inacti... Von Hippel Von Hippel-Lind... Von Hippel's Di... Von Hippel-Lind... Clear Cell Rena... Clear Cell RCC ccRCC	PT2385 Tablets	18 Years -	Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
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)	NCT03401788	VHL - Von Hippe... VHL Gene Mutati... VHL Syndrome VHL Gene Inacti... VHL-Associated ... VHL-Associated ...	Belzutifan	18 Years -	Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

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