A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)
- Registration Number
- NCT04489771
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.
The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 154
- Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear cell component
- Has measurable disease per RECIST 1.1 as assessed by BICR
- Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Has experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI). The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy
- Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
- Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC
- Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement
- Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days prior to the first dose of study intervention
- A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention
- Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤6 months from Day 1 of study drug administration or New York Heart Association Class III or IV congestive heart failure
- Has moderate to severe hepatic impairment (Child-Pugh B or C)
- Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
- Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
- Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations
- Has received prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor
- Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤2 weeks before randomization
- Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks before randomization
- Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
- Has had major surgery ≤3 weeks prior to first dose of study intervention
- Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
- Is currently participating in a study of an investigational agent or is currently using an investigational device
- Has an active infection requiring systemic therapy
- Has active tuberculosis (TB)
- Has a diagnosis of immunodeficiency
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not the best interest of the participant to participate, in the opinion of the treating investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belzutifan 200 mg Belzutifan Participants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation. Belzutifan 120 mg Belzutifan Participants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) Up to approximately 27 months ORR was defined as the percentage of participants who had a 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 RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by blinded independent central review based on RECIST 1.1 was presented.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR Up to approximately 27 months For participants who demonstrated a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review was presented.
Clinical Benefit Rate (CBR) Per RECIST 1.1 as Assessed by BICR Up to approximately 27 months CBR is defined as the percentage of participants who have a 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) or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) ≥6 months per RECIST 1.1. The percentage of participants with CBR will be presented.
Number of Participants Who Experience One or More Adverse Events (AEs) Up to approximately 27 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one or more AEs was presented.
Progression-Free Survival (PFS) According to RECIST 1.1 as Assessed by BICR Up to approximately 27 months PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥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 ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by blinded independent central review was presented.
Overall Survival (OS) Up to approximately 27 months OS was defined as the time from randomization to death due to any cause.
Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 26 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE was presented.
Maximum Plasma Concentration (Cmax) of Belzutifan Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only Blood samples were obtained at designated time points for the determination of the Cmax of belzutifan.
Trough Plasma Concentration (Ctrough) of Belzutifan Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only Blood samples were obtained at designated time points for the determination of the Ctrough of belzutifan.
Trial Locations
- Locations (48)
Weinberg Cancer Institute at Franklin Square ( Site 0007)
🇺🇸Baltimore, Maryland, United States
University of Texas Southwestern Medical Center at Dallas ( Site 0004)
🇺🇸Dallas, Texas, United States
Inova Schar Cancer Institute ( Site 0001)
🇺🇸Fairfax, Virginia, United States
Royal Free London NHS Foundation Trust ( Site 9003)
🇬🇧London, England, United Kingdom
Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023)
🇺🇸Miami, Florida, United States
Huntsman Cancer Institute ( Site 0037)
🇺🇸Salt Lake City, Utah, United States
Georgetown University Medical Center ( Site 0002)
🇺🇸Washington, District of Columbia, United States
Universitair Medisch Centrum Utrecht ( Site 5004)
🇳🇱Utrecht, Netherlands
City Clinical Oncology Hospital No. 1 ( Site 6004)
🇷🇺Moscow, Moskva, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Eastern Health - Box Hill Hospital ( Site 1003)
🇦🇺Box Hill, Victoria, Australia
Peninsula Health Frankston Hospital ( Site 1001)
🇦🇺Frankston, Victoria, Australia
Grand Hopital de Charleroi ( Site 2005)
🇧🇪Charleroi, Hainaut, Belgium
UZ Gent ( Site 2004)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Cork University Hospital ( Site 9053)
🇮🇪Cork, Ireland
Tallaght University Hospital ( Site 9051)
🇮🇪Dublin, Ireland
Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site
🇷🇺Moscow, Moskva, Russian Federation
Sanford Cancer Center Oncology Clinic ( Site 0031)
🇺🇸Sioux Falls, South Dakota, United States
CHU de Liege ( Site 2002)
🇧🇪Liège, Liege, Belgium
UZ Leuven ( Site 2001)
🇧🇪Leuven, Vlaams-Brabant, Belgium
Cancer Partners of Nebraska ( Site 0003)
🇺🇸Lincoln, Nebraska, United States
Urology Associates ( Site 0015)
🇺🇸Nashville, Tennessee, United States
UT West Cancer Center ( Site 0032)
🇺🇸Germantown, Tennessee, United States
General Hospital of Athens "Alexandra" ( Site 1102)
🇬🇷Athens, Attiki, Greece
Rambam Medical Center ( Site 4001)
🇮🇱Haifa, Israel
Rabin Medical Center ( Site 4002)
🇮🇱Petach Tikva, Israel
University General Hospital of Larissa ( Site 1101)
🇬🇷Larissa, Thessalia, Greece
Erasmus MC ( Site 5000)
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Clinical Research Center of specialized types medical care-Oncology ( Site 6002)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Isala klinieken ( Site 5002)
🇳🇱Zwolle, Overijssel, Netherlands
Norton Cancer Institute - St. Matthews ( Site 0025)
🇺🇸Louisville, Kentucky, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012)
🇺🇸Omaha, Nebraska, United States
New York Oncology Hematology P.C ( Site 0028)
🇺🇸Albany, New York, United States
Fox Chase Cancer Center ( Site 0026)
🇺🇸Philadelphia, Pennsylvania, United States
Roswell Park Cancer Institute ( Site 0038)
🇺🇸Buffalo, New York, United States
Baylor Scott & White Medical Center - Temple ( Site 0013)
🇺🇸Temple, Texas, United States
Blue Ridge Cancer Care - Roanoke ( Site 0017)
🇺🇸Roanoke, Virginia, United States
Macquarie University ( Site 1007)
🇦🇺Macquarie University, New South Wales, Australia
Kadlec Clinic Hematology and Oncology ( Site 0008)
🇺🇸Kennewick, Washington, United States
GZA Sint Augustinus ( Site 2003)
🇧🇪Wilrijk, Antwerpen, Belgium
Athens University Hospital ATTIKON ( Site 1100)
🇬🇷Chaidari, Attiki, Greece
Soroka Medical Center ( Site 4004)
🇮🇱Beer Sheva, Israel
Sourasky Medical Center ( Site 4003)
🇮🇱Tel Aviv, Israel
Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)
🇳🇱Maastricht, Limburg, Netherlands
Imperial College Healthcare NHS Trust ( Site 9004)
🇬🇧London, London, City Of, United Kingdom
Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001)
🇬🇧Nottingham, United Kingdom
Churchill Hospital ( Site 9000)
🇬🇧Oxford, Oxfordshire, United Kingdom