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RECRUITINGPhase 3INTERVENTIONAL

A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib. The goal of this study is to learn if: People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.

Who May Be Eligible (Plain English)

Who May Qualify: The main inclusion criteria include but are not limited to the following: - Has a diagnosed by tissue sample (biopsy-confirmed) diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) - Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) - Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy - Has received no other previous cancer treatment that works throughout the body (like chemotherapy) for their RCC except for their adjuvant anti-PD-1/L1 therapy Who Should NOT Join This Trial: The main exclusion criteria include but are not limited to the following: - Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability - Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization - Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram - Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications - Has current pneumonitis/interstitial lung disease ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) * Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) * Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy * Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability * Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization * Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram * Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications * Has current pneumonitis/interstitial lung disease * Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization * Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation * Has a serious active nonhealing wound/ulcer/bone fracture * Has a requirement for hemodialysis or peritoneal dialysis * Has history of human immunodeficiency virus infection * Has hepatitis B or hepatitis C virus * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Treatments Being Tested

DRUG

Belzutifan

Administered orally QD

DRUG

Zanzalintinib

Administered orally QD

DRUG

Cabozantinib

Administered orally QD

Locations (20)

Hospital Italiano de Buenos Aires. ( Site 0203)
Caba, Buenos Aires, Argentina
Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)
Caba, Buenos Aires, Argentina
Instituto Alexander Fleming ( Site 0202)
CABA, Buenos Aires, Argentina
Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 0208)
Caba., Buenos Aires F.D., Argentina
Sanatorio Parque ( Site 0201)
Rosario, Santa Fe Province, Argentina
Instituto de Oncología de Rosario ( Site 0209)
Rosario, Santa Fe Province, Argentina
Hospital Privado Universitario de Córdoba ( Site 0207)
Córdoba, Argentina
Macquarie University-MQ Health Clinical Trials Unit ( Site 2100)
Sydney, New South Wales, Australia
Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0600)
Linz, Upper Austria, Austria
Medizinische Universitat Wien ( Site 0601)
Vienna, Austria
Cliniques Universitaires Saint-Luc ( Site 0703)
Brussels, Bruxelles-Capitale, Region de, Belgium
Ziekenhuis Oost-Limburg, Campus St.-Jan ( Site 0701)
Genk, Limburg, Belgium
UZ Gent ( Site 0702)
Ghent, Oost-Vlaanderen, Belgium
UZ Leuven ( Site 0700)
Leuven, Vlaams-Brabant, Belgium
Masarykuv onkologicky ustav ( Site 0903)
Brno, Brno-mesto, Czechia
Fakultni nemocnice Ostrava ( Site 0904)
Ostrava, Ostrava Mesto, Czechia
Nemocnice České Budějovice ( Site 0905)
České Budějovice, Czechia
Fakultni nemocnice Hradec Kralove ( Site 0902)
Hradec Králové, Czechia
Fakultni nemocnice Olomouc ( Site 0901)
Olomouc, Czechia
Vseobecna fakultni nemocnice v Praze ( Site 0906)
Prague, Czechia