RecruitingNCT07489495ClinicalTrials.gov record

A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)

Carcinoma, Renal Cell

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THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Phase 3
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 758 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC).

A 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.

The 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

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)
Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
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

Exclusion Criteria:

For exclusion criteria: The main exclusion criteria include but are not limited to the following:

Has any of the following: a pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Has 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
Has current pneumonitis/interstitial lung disease
Has a history of human immunodeficiency virus infection
Has Hepatitis B or Hepatitis C virus infection
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Has a history of solid organ transplant
Has not adequately recovered from major surgery or has ongoing surgical complications

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Triple masked

Belzutifan + Zanzalintinib

Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.

Drug: Belzutifan · Drug: Zanzalintinib

Belzutifan + Placebo

Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.

Drug: Belzutifan · Drug: Placebo

Belzutifan DRUG

Tablet for oral administration.

Zanzalintinib DRUG

Tablet for oral administration.

Placebo DRUG

Zanzalintinib-matching placebo tablet for oral administration.

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Progression-free Survival (PFS)

Time frame: Up to approximately 30 months

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.

Overall Survival (OS)

Time frame: Up to approximately 50 months

OS is defined as the time from randomization to death due to any cause.

Secondary measures

Objective Response Rate (ORR)

Time frame: Up to approximately 30 months

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.

Duration of Response (DOR)

Time frame: Up to approximately 30 months

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.

Number of Participants Who Experience One or More Adverse Events (AEs)

Time frame: Up to approximately 25 months

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.

Number of Participants who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 24 months

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

Time frame: Baseline and up to approximately 25 months

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.

Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score

Time frame: Baseline and up to approximately 25 months

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.

Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score

Time frame: Baseline and up to approximately 25 months

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.

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

Time frame: Baseline and 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. 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.

Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

Time frame: Up to approximately 25 months

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.

TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

Time frame: Up to approximately 25 months

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.

TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score

Time frame: Up to approximately 25 months

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.

TTD in Disease Symptoms Using the FKSI-DRS (Items 1-9) Score

Time frame: 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. 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.

No results are flagged as posted.

Review the complete result tables and limitations in the official record.

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Research locations (111)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

Find a location in this study

111 locations

City of Hope Comprehensive Cancer Center ( Site 0129)Duarte, California, United StatesRecruiting

Study CoordinatorCONTACT877-817-9982

What this study involves

About the research

Who may be able to participate?

Treatment, groups and participation

What researchers are measuring

Primary measures

Secondary measures

Research locations (111)

Study team and timeline

Official study contacts

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