The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,653
Pembrolizumab 400 mg administered Q6W via IV infusion
Belzutifan 120 mg administered QD via oral tablet
Pembrolizumab/quavonlimab is a co-formulated product composed of pembrolizumab 400 mg in combination with quavonlimab 25 mg, administered Q6W via IV infusion
Lenvatinib 20 mg administered QD via oral capsule
The University of Alabama at Birmingham ( Site 0010)
Birmingham, Alabama, United States
UC San Diego ( Site 0050)
La Jolla, California, United States
Cedars Sinai Medical Center ( Site 0027)
Los Angeles, California, United States
University of California Irvine ( Site 0029)
Orange, California, United States
UCLA Hematology Oncology Santa Monica ( Site 0048)
Santa Monica, California, United States
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
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 BICR based on RECIST 1.1 will be presented.
Time frame: Up to approximately 46 months
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 66 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
ORR is defined as the percentage of participants who have a 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 RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 will be presented.
Time frame: Up to approximately 46 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed 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 PD or death due to any cause, whichever occurs first. 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 ≥5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR based on RECIST 1.1 will be presented.
Time frame: Up to approximately 66 months
Number of Participants Who Experienced At least One Adverse Event (AE)
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. The number of participants who experience at least one AE will be presented.
Time frame: Up to approximately 66 months
Number of Participants Who Discontinue Study Treatment Due to an AE
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. The number of participants who discontinue study treatment due to an AE will be presented.
Time frame: Up to approximately 66 months
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Hartford Hospital ( Site 0024)
Hartford, Connecticut, United States
Advent Health Hematology & Oncology ( Site 0003)
Orlando, Florida, United States
University Cancer & Blood Center, LLC ( Site 0057)
Athens, Georgia, United States
Emory University Winship Cancer Institute ( Site 0012)
Atlanta, Georgia, United States
Rush University Medical Center ( Site 0040)
Chicago, Illinois, United States
...and 252 more locations