A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)

Carcinoma, Renal Cell Clinical Trial

Official title:

Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04489771
• Other study ID #: 6482-013
• Secondary ID: MK-6482-0132020-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 13, 2020
• Est. completion date: October 4, 2025

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 154
• Est. completion date: October 4, 2025
• Est. primary completion date: February 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)-2a 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Belzutifan
Oral administration

Locations

Country	Name	City	State
Australia	Eastern Health - Box Hill Hospital ( Site 1003)	Box Hill	Victoria
Australia	Peninsula Health Frankston Hospital ( Site 1001)	Frankston	Victoria
Australia	Macquarie University ( Site 1007)	Macquarie University	New South Wales
Belgium	Grand Hopital de Charleroi ( Site 2005)	Charleroi	Hainaut
Belgium	UZ Gent ( Site 2004)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 2001)	Leuven	Vlaams-Brabant
Belgium	CHU de Liege ( Site 2002)	Liège	Liege
Belgium	GZA Sint Augustinus ( Site 2003)	Wilrijk	Antwerpen
Greece	General Hospital of Athens "Alexandra" ( Site 1102)	Athens	Attiki
Greece	Athens University Hospital ATTIKON ( Site 1100)	Chaidari	Attiki
Greece	University General Hospital of Larissa ( Site 1101)	Larissa	Thessalia
Ireland	Cork University Hospital ( Site 9053)	Cork
Ireland	Tallaght University Hospital ( Site 9051)	Dublin
Israel	Soroka Medical Center ( Site 4004)	Beer Sheva
Israel	Rambam Medical Center ( Site 4001)	Haifa
Israel	Rabin Medical Center ( Site 4002)	Petach Tikva
Israel	Sourasky Medical Center ( Site 4003)	Tel Aviv
Netherlands	Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)	Amsterdam	Noord-Holland
Netherlands	Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)	Maastricht	Limburg
Netherlands	Erasmus MC ( Site 5000)	Rotterdam	Zuid-Holland
Netherlands	Universitair Medisch Centrum Utrecht ( Site 5004)	Utrecht
Netherlands	Isala klinieken ( Site 5002)	Zwolle	Overijssel
Russian Federation	City Clinical Oncology Hospital No. 1 ( Site 6004)	Moscow	Moskva
Russian Federation	Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site	Moscow	Moskva
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Clinical Research Center of specialized types medical care-Oncology ( Site 6002)	Saint-Petersburg	Sankt-Peterburg
United Kingdom	Imperial College Healthcare NHS Trust ( Site 9004)	London	London, City Of
United Kingdom	Royal Free London NHS Foundation Trust ( Site 9003)	London	England
United Kingdom	Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001)	Nottingham
United Kingdom	Churchill Hospital ( Site 9000)	Oxford	Oxfordshire
United States	New York Oncology Hematology P.C ( Site 0028)	Albany	New York
United States	Weinberg Cancer Institute at Franklin Square ( Site 0007)	Baltimore	Maryland
United States	Roswell Park Cancer Institute ( Site 0038)	Buffalo	New York
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	UT West Cancer Center ( Site 0032)	Germantown	Tennessee
United States	Kadlec Clinic Hematology and Oncology ( Site 0008)	Kennewick	Washington
United States	Cancer Partners of Nebraska ( Site 0003)	Lincoln	Nebraska
United States	Norton Cancer Institute - St. Matthews ( Site 0025)	Louisville	Kentucky
United States	Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023)	Miami	Florida
United States	Urology Associates ( Site 0015)	Nashville	Tennessee
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012)	Omaha	Nebraska
United States	Fox Chase Cancer Center ( Site 0026)	Philadelphia	Pennsylvania
United States	Blue Ridge Cancer Care - Roanoke ( Site 0017)	Roanoke	Virginia
United States	Huntsman Cancer Institute ( Site 0037)	Salt Lake City	Utah
United States	Sanford Cancer Center Oncology Clinic ( Site 0031)	Sioux Falls	South Dakota
United States	Baylor Scott & White Medical Center - Temple ( Site 0013)	Temple	Texas
United States	Georgetown University Medical Center ( Site 0002)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Greece,  Ireland,  Israel,  Netherlands,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Up to approximately 27 months
Secondary	Progression-Free Survival (PFS) According to RECIST 1.1 as Assessed by BICR	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.	Up to approximately 27 months
Secondary	Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	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.	Up to approximately 27 months
Secondary	Clinical Benefit Rate (CBR) Per RECIST 1.1 as Assessed by BICR	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.	Up to approximately 27 months
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 27 months
Secondary	Number of Participants Who Experience One or More Adverse Events (AEs)	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.	Up to approximately 27 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	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.	Up to approximately 26 months
Secondary	Maximum Plasma Concentration (Cmax) of Belzutifan	Blood samples were obtained at designated time points for the determination of the Cmax of belzutifan.	Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only
Secondary	Trough Plasma Concentration (Ctrough) of Belzutifan	Blood samples were obtained at designated time points for the determination of the Ctrough of belzutifan.	Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary