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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
747
Immediate-release 40 mg tablet
Capsule available in 4 mg and 10 mg dosages
Tablet available in 20 mg, 40 mg and 60 mg dosages
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)
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.
Time frame: Up to approximately 34 months
Overall Survival (OS)
OS is defined as time from randomization to death due to any cause.
Time frame: Up to approximately 44 months
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)
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.
Time frame: Up to approximately 24 months
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)
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.
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Ironwood Cancer & Research Centers ( Site 0077)
Chandler, Arizona, United States
Cedars Sinai Medical Center ( Site 0027)
Los Angeles, California, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0048)
Los Angeles, California, United States
St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095)
Orange, California, United States
University of California, Irvine ( Site 0029)
Orange, California, United States
Providence Saint John's Health Center ( Site 0083)
Santa Monica, California, United States
Georgetown University Medical Center ( Site 0006)
Washington D.C., District of Columbia, United States
AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0003)
Orlando, Florida, United States
Orlando Health, Inc. ( Site 0035)
Orlando, Florida, United States
University Cancer & Blood Center, LLC ( Site 0057)
Athens, Georgia, United States
...and 174 more locations
Time frame: Up to approximately 44 months
Number of Participants Who Experienced One or More Adverse Events (AEs)
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.
Time frame: Up to approximately 44 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
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.
Time frame: Up to approximately 44 months