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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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VHL, VHL Gene Mutation, 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

Intervention / Treatment
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* Drug: PT2385 Tablets


Participation Criteria
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Eligibility Criteria
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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: Has had prior radiotherapy or systemic anti cancer therapy for ccRCC (includes anti-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 patient 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label Phase 2 study that will be conducted with a 2-stage design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT2385 Tablets<br>Twenty-five patients will be enrolled in each stage of a two-stage design | Drug: PT2385 Tablets<br>* PT2385 inhibits HIF-2α and is a novel approach to treatment of VHL disease-associated ccRCC.<br>* Other names: PT2385, PT-2385, HIF-2a, MK-3795;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate (ORR) in VHL disease-associated ccRCC tumors | 4-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression free survival (PFS) in VHL disease-associated ccRCC tumors | 4-5 years | 
| Duration of Response (DOR) | Duration of response (DOR) in VHL disease-associated ccRCC tumors | 4-5 years | 
| Time to Response (TTR) | Time to response (TTR) in VHL disease-associated ccRCC tumors | 4-5 years | 
| Number of Participants who Experience One or More Adverse Events (AEs) | 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. | Up to approximately 5 years | 
| Number of Participants who Discontinue Study Intervention Due to an AE. | 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. | Up to approximately 5 years |