Carcinoma, Renal Cell Clinical Trial
Official title:
Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma
| Verified date | January 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| 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 |
| 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 |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Belgium, Greece, Ireland, Israel, Netherlands, Russian Federation, United Kingdom,
| 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 |
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