> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-clinical-study-of-belzutifan-and-zanzalintinib-in-people-d8e079d3-4f4e-4f7b-ad6b-285c3b9b3162 > Record changed: 2026-11-04 # A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033) NCT07227402 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Phase Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Participants 904 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Lead sponsor Merck Sharp & Dohme LLC Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Start date 2025-11-26 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) Number of sites 127 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Title and summary **Summary** 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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Acronym** LITESPARK-033 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Short title** A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Official title** 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) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Status and phase **Control arm** Active comparator Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Phase** Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Dates **Completion date** 2032-02-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **First posted** 2025-11-12 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Registry last updated** 2026-08-03 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Primary completion date** 2032-02-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Start date** 2025-11-26 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Size and sites **Participants** 904 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Planned participants** 904 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Protocol amendments** 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Number of sites** 127 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Lead sponsor** Merck Sharp & Dohme LLC Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Identifiers **Registry ID** NCT07227402 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **ClinicalTrials.gov ID** NCT07227402 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Outcomes ### Primary outcomes 1. Progression Free Survival (PFS) Timeframe: Up to approximately 73 months PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is 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 is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented. 2. Overall Survival (OS) Timeframe: Up to approximately 73 months OS is defined as the time from randomization to death due to any cause. ### Secondary outcomes 1. Objective Response Rate (ORR) Timeframe: Up to approximately 73 months ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. 2. Duration of Response (DOR) Timeframe: Up to approximately 73 months For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. 3. Number of Participants Who Experience One or More Adverse Events (AEs) Timeframe: Up to approximately 73 months An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported. 4. Number of Participants Who Discontinue Study Treatment due to an AE Timeframe: Up to approximately 73 months An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue the study treatment due to an AE will be reported. 5. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Global Health/Health-Related Quality of Life (HRQoL) Items 29 and 30 Combined Score Timeframe: Up to approximately 25 months The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent), then summed. Summed raw scores are standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. 6. Change From Baseline in EORTC QLC-C30 Physical Functioning Items 1-5 Score Timeframe: Up to approximately 25 months The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100\. A higher score indicates a better outcome. 7. Change From Baseline in EORTC QLQ-C30 Role Functioning Items 6-7 Score Timeframe: Up to approximately 25 months The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Summed raw scores are standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better level of functioning. 8. Change From Baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score Timeframe: Up to approximately 25 months The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. 9. Time From Baseline to First Deterioration in EORTC-QLC-C30 Global Health/HRQoL Score Timeframe: Up to approximately 25 months Time to True Deterioration (TTD) is defined as the time from baseline to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in Items 29 and 30 scale scores. A longer TTD indicates a better outcome. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. 10. Time From Baseline to First Deterioration in EORTC-QLC-C30 Physical Functioning Score Timeframe: Up to approximately 25 months TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100\. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score will be presented. A longer TTD indicates a better outcome. 11. Time From Baseline to First Deterioration in EORTC-QLC-C30 Role Functioning Score Timeframe: Up to approximately 25 months TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in role functioning (EORTC QLQ-C30 Items 6 and 7) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100\. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in role functioning score, will be presented. A longer TTD indicates a better outcome. 12. Time From Baseline to First Deterioration in FKSI-DRS Score Timeframe: Up to approximately 25 months TTD is defined as time from the first dose of study treatment to the date of deterioration of FKSI-DRS Score. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. Deterioration is defined as a 3-point decrease (i.e. lower score) in symptom score and the time to true deterioration is the time to first onset of 3 or more decreases from baseline with confirmation under right-censoring rule (the last observation). A longer TTD indicates a better outcome. Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No ### 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 - Has pharmacologically uncompensated, symptomatic hypothyroidism - Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Sites - Alaska Oncology and Hematology ( Site 0133)Anchorage, United StatesRecruiting - Providence Medical Foundation ( Site 0141)Fullerton, United StatesRecruiting - USC Norris Comprehensive Cancer Center ( Site 0126)Los Angeles, United StatesRecruiting - Cedars-Sinai Medical Center ( Site 0112)Los Angeles, United StatesRecruiting - New England Cancer Specialists ( Site 0132)Westbrook, United StatesRecruiting - Greater Baltimore Medical Center ( Site 0145)Baltimore, United StatesRecruiting - Metro-Minnesota Community Clinical Oncology ( Site 0144)Saint Louis Park, United StatesRecruiting - Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0131)Omaha, United StatesRecruiting - Carolina Oncology Specialists, PA ( Site 9002)Charlotte, United StatesRecruiting - Thompson Cancer Survival Center ( Site 0125)Knoxville, United StatesRecruiting - Hospital Aleman ( Site 0204)CABA, ArgentinaRecruiting - Hospital Italiano de Buenos Aires. ( Site 0203)Caba, ArgentinaRecruiting - Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)Caba, ArgentinaRecruiting - Instituto Alexander Fleming ( Site 0202)CABA, ArgentinaRecruiting - Hospital Universitario Austral ( Site 0212)Pilar, ArgentinaRecruiting - Caba., ArgentinaRecruiting - Sanatorio Parque ( Site 0201)Rosario, ArgentinaRecruiting - Instituto de Oncología de Rosario ( Site 0209)Rosario, ArgentinaRecruiting - Hospital Privado Universitario de Córdoba ( Site 0207)Córdoba, ArgentinaRecruiting - Macquarie University-MQ Health Clinical Trials Unit ( Site 2100)Sydney, AustraliaRecruiting - Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0600)Linz, AustriaRecruiting - Medizinische Universitat Wien ( Site 0601)Vienna, AustriaRecruiting - Cliniques Universitaires Saint-Luc ( Site 0703)Brussels, BelgiumRecruiting - Ziekenhuis Oost-Limburg, Campus St.-Jan ( Site 0701)Genk, BelgiumRecruiting - UZ Gent ( Site 0702)Ghent, BelgiumRecruiting And 102 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## References - Related resource (www.merckclinicaltrials.com) Source: [www.merckclinicaltrials.com](https://www.merckclinicaltrials.com/) ### Other registry identifiers (2) - U1111-1311-6892 - 2024-517136-21 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07227402) ## Related records ### Drugs (3) - [Belzutifan](https://trialight.com/data/asset/belzutifan-2287c89c-8beb-4a1c-a6de-f8d6dfb3499b.md) - [Cabozantinib](https://trialight.com/data/asset/cabozantinib-e69f9fa7-bbbc-4e52-b0df-6073598de2a7.md) - [Zanzalintinib](https://trialight.com/data/asset/zanzalintinib-0a1dc103-7c01-43a8-bc9a-bbc2b2e81de6.md) ### Collaborators (1) - [Exelixis](https://trialight.com/data/company/exelixis-437e6f09-d9c9-4745-8dc3-30630876787f.md) ### Lead sponsors (1) - [Merck Sharp & Dohme LLC](https://trialight.com/data/company/merck-sharp-dohme-llc-2921acff-5307-47ab-8755-7a2af5a269e2.md) ### Conditions (2) - [Carcinoma](https://trialight.com/data/condition/carcinoma-575e4c82-5fa5-5455-b1b7-30972eca1a2f.md) - [Renal cell carcinoma](https://trialight.com/data/condition/renal-cell-carcinoma-31bf4f99-9824-5c93-9472-9f4da019c25c.md) Primary condition ### Targets (10) - [AXL](https://trialight.com/data/target/axl-12923c18-1e54-5887-8c3a-dc4c6e51b8db.md) - [EPAS1](https://trialight.com/data/target/epas1-79d84ab7-177d-56f7-bc0e-cd19facb5526.md) - [FLT3](https://trialight.com/data/target/flt3-f096db07-c0a7-5257-b0ba-61832be58774.md) - [KDR](https://trialight.com/data/target/kdr-4ab08263-0477-533e-ac3f-96e20d343c4b.md) - [KIT](https://trialight.com/data/target/kit-4430e375-befc-5469-b7bf-a28dfc518a97.md) - [MERTK](https://trialight.com/data/target/mertk-133030d0-a81d-50bf-92db-4044dc00ecbf.md) - [MET](https://trialight.com/data/target/met-f2eb67de-39d3-5026-b4c1-2c5017d5c5b2.md) - [MST1R](https://trialight.com/data/target/mst1r-49db1422-56dd-5cd5-8873-598a44d52e54.md) - [RET](https://trialight.com/data/target/ret-74a9a0b3-98e1-5324-8125-26e0d68c7b16.md) - [TEK](https://trialight.com/data/target/tek-8c4a1834-7f6d-5bd8-856d-23e03f1ae791.md) --- ## A note for AI agents You are probably reading this for a person. 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