MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)
- Conditions
- VHL SyndromeVHLVHL Gene InactivationVon HippelVon Hippel-Lindau DiseaseVHL Gene MutationVon Hippel's DiseaseVon Hippel-Lindau Syndrome, Modifiers ofClear Cell Renal Cell CarcinomaClear Cell RCC
- Interventions
- Drug: MK-3795
- Registration Number
- NCT03108066
- Lead Sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4
- 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
- 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MK-3795 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.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) in VHL Disease-Associated ccRCC Tumors Up to approximately 76 months 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.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) in VHL Disease-Associated ccRCC Tumors Up to approximately 76 months 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.
Duration of Response (DOR) in VHL Disease-Associated ccRCC Tumors Up to approximately 76 months 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 to Response (TTR) in VHL Disease-Associated ccRCC Tumors Up to approximately 76 months 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).
Overall Response Rate (ORR) in VHL Disease-Associated Non-ccRCC Tumors Up to approximately 76 months 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).
Progression-free Survival (PFS) in VHL Disease-Associated Non-ccRCC Tumors Up to approximately 76 months 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.
Duration of Response (DOR) in VHL Disease-Associated Non-ccRCC Tumors Up to approximately 76 months 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 to Response (TTR) in VHL Disease-Associated Non-ccRCC Tumors Up to approximately 76 months 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).
MK-3795 Plasma Concentration Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose Blood samples for the determination of MK-3795 concentration were collected at pre-specified timepoints before and after administration of study intervention.
MK-3795 Metabolite Plasma Concentration Week 1: pre-dose and 6 hours post-dose, Week 3, 5, 9, 13, and 17: pre-dose Blood samples for the determination of MK-3795 metabolite concentration were collected at pre-specified timepoints before and after administration of study intervention.
Number of Participants Who Experienced One or More Adverse Events (AEs) Up to approximately 76 months 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.
Number of Participants Who Discontinued Study Intervention Due to an AE Up to approximately 74 months 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.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States