This is a Phase Ib/III, randomized, multicenter, global study evaluating the efficacy and safety of volrustomig in combination with casdatifan for the first-line (1L) treatment of participants with advanced clear cell renal cell carcinoma (ccRCC).
The primary purpose of this study is to determine the recommended Phase III dose (RP3D) of volrustomig and measure the efficacy and safety of volrustomig in combination with casdatifan compared with nivolumab plus ipilimumab in participants with advanced ccRCC (as 1L treatment). The study comprises of 2 parts - In Phase 1b part of the study, participants will be randomized in a 1:1 ratio to receive either dose 1 or dose 2 of volrustomig in combination with casdatifan. In Phase III part of the study, participants will be randomized in 1:1:1 to receive either Volrustomig (at the dose to be determined in the Phase Ib) in combination with casdatifan, volrustomig monotherapy or standard of care (nivolumab plus ipilimumab).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
1,116
Volrustomig will be administered as an intravenous (IV) infusion.
Casdatifan will be administered orally.
Nivolumab will be administered as an IV infusion.
Research Site
La Jolla, California, United States
Phase Ib: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants who received at least one dose of study treatment will be assessed.
Time frame: Approximately 39 months
Phase III: Progression-free Survival (PFS)
The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
Time frame: Approximately 38 months
Phase III: Overall Survival (OS)
The OS is defined as the time from randomization until the date of death due to any cause.
Time frame: Approximately 67 months
Phase Ib: Objective Response rate (ORR)
The ORR is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR).
Time frame: Approximately 39 months
Phase Ib: Duration of Response (DoR)
The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death due to any cause.
Time frame: Approximately 39 months
Phase Ib: Progression-free Survival (PFS)
The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
Time frame: Approximately 39 months
Phase Ib: Disease Control Rate (DCR)
The DCR is defined as the percentage of participants who have a confirmed CR or PR or who have stable disease (SD) after randomization.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ipilimumab will be administered as an IV infusion.
Research Site
Aurora, Colorado, United States
Research Site
Boston, Massachusetts, United States
Research Site
New York, New York, United States
Research Site
Cleveland, Ohio, United States
Research Site
Nashville, Tennessee, United States
Research Site
Lubbock, Texas, United States
Research Site
East Melbourne, Australia
Research Site
Elizabeth Vale, Australia
Research Site
North Adelaide, Australia
...and 22 more locations
Time frame: Approximately 39 months
Phase Ib: Volrustomig concentration in serum
To assess the serum concentration of volrustomig when administered concomitantly with casdatifan.
Time frame: Up to 27 months
Phase Ib: Casdatifan concentration in plasma
To assess the plasma concentration of casdatifan when administered concomitantly with volrustomig.
Time frame: Up to 27 months
Phase Ib: Time to Response (TTR)
The TTR is defined as the time from randomization until the first documentation of a subsequently confirmed objective response.
Time frame: Approximately 39 months
Phase III: Overall Survival
The OS is defined as the time from randomization until the date of death due to any cause.
Time frame: Approximately 67 months
Phase III: Number of participants with AEs and SAEs
Number of participants who received at least one dose of study treatment will be assessed.
Time frame: Approximately 67 months
Phase III: Time to second progression or death (PFS2)
The PFS2 is defined as the time from randomization to the earliest progression event after the start of the first subsequent therapy, or death from any cause, whichever occurs first.
Time frame: Approximately 67 months
Phase III: Objective Response rate (ORR)
The ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR.
Time frame: Approximately 67 months
Phase III: Duration of Response (DoR)
The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death due to any cause.
Time frame: Approximately 67 months
Phase III: Progression-free Survival
The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
Time frame: Approximately 67 months