Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-30 @ 9:35 PM
Study NCT ID:
NCT07489495
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-24
First Post:
2026-03-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000720612', 'term': 'belzutifan'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 758}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-17', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2030-11-27', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-20', 'studyFirstSubmitDate': '2026-03-20', 'studyFirstSubmitQcDate': '2026-03-20', 'lastUpdatePostDateStruct': {'date': '2026-03-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-11-27', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression-free Survival (PFS)', 'timeFrame': 'Up to approximately 30 months', 'description': 'PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.'}, {'measure': 'Overall Survival (OS)', 'timeFrame': 'Up to approximately 50 months', 'description': 'OS is defined as the time from randomization to death due to any cause.'}], 'secondaryOutcomes': [{'measure': 'Objective Response Rate (ORR)', 'timeFrame': 'Up to approximately 30 months', 'description': 'ORR is defined as the percentage of participants who have achieved confirmed 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 as assessed by BICR.'}, {'measure': 'Duration of Response (DOR)', 'timeFrame': 'Up to approximately 30 months', 'description': 'DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. 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.'}, {'measure': 'Number of Participants Who Experience One or More Adverse Events (AEs)', 'timeFrame': 'Up to approximately 25 months', 'description': "An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be reported."}, {'measure': 'Number of Participants who Discontinue Study Treatment Due to an AE', 'timeFrame': 'Up to approximately 24 months', 'description': "An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported."}, {'measure': 'Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score', 'timeFrame': 'Baseline and up to approximately 25 months', 'description': 'EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and 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). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 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. The change from baseline in GHS and QoL combined score will be presented.'}, {'measure': 'Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score', 'timeFrame': 'Baseline and up to approximately 25 months', 'description': 'EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 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. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score will be presented.'}, {'measure': 'Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score', 'timeFrame': 'Baseline and up to approximately 25 months', 'description': 'The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. The role functioning score is based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of Items 6 and 7 and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score will be reported.'}, {'measure': 'Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) (Items 1-9) Score', 'timeFrame': 'Baseline and up to approximately 25 months', 'description': 'The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. 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.'}, {'measure': 'Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score', 'timeFrame': 'Up to approximately 25 months', 'description': 'EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and 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. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicates a better outcome.'}, {'measure': 'TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score', 'timeFrame': 'Up to approximately 25 months', 'description': 'EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 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. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicates a better outcome.'}, {'measure': 'TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score', 'timeFrame': 'Up to approximately 25 months', 'description': 'EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to questions about their role functioning (Items 6 and 7) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of Items 6 and 7 was computed by averaging the raw scores of the 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. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in role functioning (Items 6 and 7). A longer TTD indicates a better outcome.'}, {'measure': 'TTD in Disease Symptoms Using the FKSI-DRS (Items 1-9) Score', 'timeFrame': 'Up to approximately 25 months', 'description': 'TTD is defined as time from the first dose of study treatment to the date of deterioration of FKSI-DRS score. The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. 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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Carcinoma, Renal Cell']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://www.merckclinicaltrials.com/', 'label': 'Merck Clinical Trials Information'}]}, 'descriptionModule': {'briefSummary': 'Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC).\n\nA standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone.\n\nThe goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nThe main inclusion criteria include but are not limited to the following:\n\n* Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)\n* Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)\n* Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy\n\nExclusion Criteria:\n\nFor exclusion criteria: The main exclusion criteria include but are not limited to the following:\n\n* Has any of the following: a pulse oximeter reading \\<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen\n* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention\n* Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization\n* Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram\n* Has had major surgery within 8 weeks before randomization\n* Has current pneumonitis/interstitial lung disease\n* Has a history of human immunodeficiency virus infection\n* Has Hepatitis B or Hepatitis C virus infection\n* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years\n* Has a history of solid organ transplant\n* Has not adequately recovered from major surgery or has ongoing surgical complications'}, 'identificationModule': {'nctId': 'NCT07489495', 'briefTitle': 'A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)', 'orgStudyIdInfo': {'id': '6482-034'}, 'secondaryIdInfos': [{'id': 'U1111-1311-4692', 'type': 'REGISTRY', 'domain': 'UTN'}, {'id': '2024-516993-31-00', 'type': 'REGISTRY', 'domain': 'EU CT'}, {'id': 'LITESPARK-034', 'type': 'OTHER', 'domain': 'MSD'}, {'id': 'MK-6482-034', 'type': 'OTHER', 'domain': 'MSD'}, {'id': 'LS-034', 'type': 'OTHER', 'domain': 'MSD'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Belzutifan + Zanzalintinib', 'description': 'Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.', 'interventionNames': ['Drug: Belzutifan', 'Drug: Zanzalintinib']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Belzutifan + Placebo', 'description': 'Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.', 'interventionNames': ['Drug: Belzutifan', 'Drug: Placebo']}], 'interventions': [{'name': 'Belzutifan', 'type': 'DRUG', 'otherNames': ['MK-6482', 'PT2977', 'WELIREG'], 'description': 'Tablet for oral administration.', 'armGroupLabels': ['Belzutifan + Placebo', 'Belzutifan + Zanzalintinib']}, {'name': 'Zanzalintinib', 'type': 'DRUG', 'otherNames': ['XL092'], 'description': 'Tablet for oral administration.', 'armGroupLabels': ['Belzutifan + Zanzalintinib']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Zanzalintinib-matching placebo tablet for oral administration.', 'armGroupLabels': ['Belzutifan + Placebo']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Medical Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Sharp & Dohme LLC'}]}, 'ipdSharingStatementModule': {'url': 'https://externaldatasharing-msd.com/', 'ipdSharing': 'YES', 'description': 'https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Exelixis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}