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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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
Primary outcome measure(s)
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.
Trial sites (48)
Facility
City
Region
Status
Georgetown University Medical Center ( Site 0002)
Washington D.C.
District of Columbia
Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023)
Miami
Florida
Norton Cancer Institute - St. Matthews ( Site 0025)
Louisville
Kentucky
Weinberg Cancer Institute at Franklin Square ( Site 0007)
Baltimore
Maryland
Cancer Partners of Nebraska ( Site 0003)
Lincoln
Nebraska
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012)
Omaha
Nebraska
New York Oncology Hematology P.C ( Site 0028)
Albany
New York
Roswell Park Cancer Institute ( Site 0038)
Buffalo
New York
Fox Chase Cancer Center ( Site 0026)
Philadelphia
Pennsylvania
Sanford Cancer Center Oncology Clinic ( Site 0031)
Sioux Falls
South Dakota
UT West Cancer Center ( Site 0032)
Germantown
Tennessee
Urology Associates ( Site 0015)
Nashville
Tennessee
University of Texas Southwestern Medical Center at Dallas ( Site 0004)
Dallas
Texas
Baylor Scott & White Medical Center - Temple ( Site 0013)
Temple
Texas
Huntsman Cancer Institute ( Site 0037)
Salt Lake City
Utah
Inova Schar Cancer Institute ( Site 0001)
Fairfax
Virginia
Blue Ridge Cancer Care - Roanoke ( Site 0017)
Roanoke
Virginia
Kadlec Clinic Hematology and Oncology ( Site 0008)
Kennewick
Washington
Macquarie University ( Site 1007)
Macquarie University
New South Wales
Eastern Health - Box Hill Hospital ( Site 1003)
Box Hill
Victoria
Peninsula Health Frankston Hospital ( Site 1001)
Frankston
Victoria
GZA Sint Augustinus ( Site 2003)
Wilrijk
Antwerpen
Grand Hopital de Charleroi ( Site 2005)
Charleroi
Hainaut
CHU de Liege ( Site 2002)
Liège
Liege
UZ Gent ( Site 2004)
Ghent
Oost-Vlaanderen
UZ Leuven ( Site 2001)
Leuven
Vlaams-Brabant
General Hospital of Athens "Alexandra" ( Site 1102)
Athens
Attica
Athens University Hospital ATTIKON ( Site 1100)
Chaïdári
Attica
University General Hospital of Larissa ( Site 1101)
Larissa
Thessaly
Cork University Hospital ( Site 9053)
Cork
Ireland
Tallaght University Hospital ( Site 9051)
Dublin
Ireland
Soroka Medical Center ( Site 4004)
Beersheba
Israel
Rambam Medical Center ( Site 4001)
Haifa
Israel
Rabin Medical Center ( Site 4002)
Petah Tikva
Israel
Sourasky Medical Center ( Site 4003)
Tel Aviv
Israel
Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)
Maastricht
Limburg
Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)
Amsterdam
North Holland
Isala klinieken ( Site 5002)
Zwolle
Overijssel
Erasmus MC ( Site 5000)
Rotterdam
South Holland
Universitair Medisch Centrum Utrecht ( Site 5004)
Utrecht
Netherlands
+ 8 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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