NCT04586231 · CITED IN SOURCE DOCUMENTS

A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-05-05

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: Inclusion Criteria: * Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC). * Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose. * Measurable disease per RECIST 1.1 criteria as assessed by local study investigator. * Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization. * Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease * Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC. * 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 belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib. * A female participant is eligible to participate if they are 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 in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm. * Adequately controlled blood pressure. * Adequate organ function. Exclusion Criteria: * A pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen. * 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 (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy. * Known central nervous system (CNS) metastases and/or carcinomatous meningitis. * Clinically significant cardiac disease within 6 months of first dose of study intervention. * Prolongation of QTc interval to \>480 ms. * Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable. * Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula. * Moderate to severe hepatic impairment. * History of significant bleeding within 3 months before randomization. * History of solid organ transplantation. * Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study. * Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption). * Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations. * Received colony-stimulating factors \[eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)\] within 28 days before randomization. * Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor. * Prior treatment with lenvatinib. * Prior treatment with cabozantinib. * Currently participating in a study of an investigational agent or using an investigational device. * Active infection requiring systemic therapy. * History of human immunodeficiency virus (HIV) infection. * History of hepatitis B or known active hepatitis C infection.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
intervention Names
Drug: Belzutifan
Drug: Lenvatinib
label
Belzutifan + Lenvatinib
type
EXPERIMENTAL
description
Cabozantinib 60 mg orally once a day
intervention Names
Drug: Cabozantinib
label
Cabozantinib
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Belzutifan + Lenvatinib
description
Immediate-release 40 mg tablet
name
Belzutifan
other Names
PT2977
MK-6482
WELIREG™
type
DRUG
arm Group Labels
Belzutifan + Lenvatinib
description
Capsule available in 4 mg and 10 mg dosages
name
Lenvatinib
other Names
Lenvima
E7080
MK-7902
type
DRUG
arm Group Labels
Cabozantinib
description
Tablet available in 20 mg, 40 mg and 60 mg dosages
name
Cabozantinib
other Names
Cabometyx
Cometriq
XL184
BMS-907351
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 747
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS is 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 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 will be presented.
measure
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
time Frame
Up to approximately 34 months
description
OS is defined as time from randomization to death due to any cause.
measure
Overall Survival (OS)
time Frame
Up to approximately 44 months

secondary Outcomes

description
ORR 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) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.
measure
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)
time Frame
Up to approximately 24 months
description
For participants who demonstrate 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 is 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 will be presented.
measure
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
time Frame
Up to approximately 44 months
description
An adverse event (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.
measure
Number of Participants Who Experienced One or More Adverse Events (AEs)
time Frame
Up to approximately 44 months
description
An adverse event (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.
measure
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
time Frame
Up to approximately 44 months

Full study description

brief Summary: This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Source references

references

citation
Motzer RJ, McDermott R, Park SH, Burotto M, Iacovelli R, Verzoni E, Suarez C, Eto M, Cutuli HJ, Porta C, Kopp RM, Rottey S, Velasco G, Valderrama BP, Azad AA, Giorgi U, Pavic M, Tomczak P, Figlin R, Westgeest HM, Guida A, Necchi A, Schutz FA, Suelmann BBM, Haanen JBAG, Yuan SS, Perini RF, Wang D, Heng DYC, Schmidinger M; LITESPARK-011 Investigators. Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial. Lancet. 2026 Aug 12:S0140-6736(26)01089-5. doi: 10.1016/S0140-6736(26)01089-5. Online ahead of print.
pmid
42586114
type
DERIVED
citation
Motzer RJ, Schmidinger M, Eto M, Suarez C, Figlin R, Liu Y, Perini R, Zhang Y, Heng DY. LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Future Oncol. 2023 Jan;19(2):113-121. doi: 10.2217/fon-2022-0802. Epub 2023 Feb 8.
pmid
36752726
type
DERIVED