A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC
- Conditions
- Advanced Clear Cell Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT07000149
- Lead Sponsor
- AstraZeneca
- Brief Summary
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).
- Detailed Description
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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1116
- Histologically or cytologically confirmed RCC with clear cell component.
- Advanced/metastatic RCC or recurrent disease that has not previously been treated with systemic therapy in the 1L setting.
- Karnofsky Performance Status ≥ 70%.
- Provision of acceptable tumor sample.
- At least one lesion that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements.
- History of leptomeningeal disease or spinal cord compression.
- Symptomatic brain metastases.
- Medical history of severe chronic obstructive pulmonary disease.
- Active or prior documented autoimmune or inflammatory disorders.
- Prior systemic therapy for advanced/metastatic RCC. Note - Other inclusion and exclusion criteria may apply as stated in the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1A (Volrustomig Dose 1 + Casdatifan) Volrustomig Participants will receive dose 1 of volrustomig in combination with casdatifan. Arm 1A (Volrustomig Dose 1 + Casdatifan) Casdatifan Participants will receive dose 1 of volrustomig in combination with casdatifan. Arm 1B (Volrustomig Dose 2 + Casdatifan) Volrustomig Participants will receive dose 2 of volrustomig in combination with casdatifan. Arm 1B (Volrustomig Dose 2 + Casdatifan) Casdatifan Participants will receive dose 2 of volrustomig in combination with casdatifan. Arm 3A (Volrustomig Dose X + Casdatifan) Volrustomig Participants will receive Volrustomig at the dose to be determined in the Phase Ib part of the study, in combination with casdatifan. Arm 3C (Nivolumab + Ipilimumab) Nivolumab Participants will receive nivolumab plus ipilimumab as standard of care treatment. Arm 3C (Nivolumab + Ipilimumab) Ipilimumab Participants will receive nivolumab plus ipilimumab as standard of care treatment. Arm 3A (Volrustomig Dose X + Casdatifan) Casdatifan Participants will receive Volrustomig at the dose to be determined in the Phase Ib part of the study, in combination with casdatifan. Arm 3B (Volrustomig Dose 1) Volrustomig Participants will receive dose 1 of volrustomig.
- Primary Outcome Measures
Name Time Method Phase III: Overall Survival (OS) Approximately 67 months The OS is defined as the time from randomization until the date of death due to any cause.
Phase Ib: Number of participants with adverse events (AEs) and serious adverse events (SAEs) Approximately 39 months Number of participants who received at least one dose of study treatment will be assessed.
Phase III: Progression-free Survival (PFS) Approximately 38 months The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
- Secondary Outcome Measures
Name Time Method Phase III: Number of participants with AEs and SAEs Approximately 67 months Number of participants who received at least one dose of study treatment will be assessed.
Phase Ib: Objective Response rate (ORR) Approximately 39 months The ORR is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR).
Phase Ib: Duration of Response (DoR) Approximately 39 months 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.
Phase Ib: Progression-free Survival (PFS) Approximately 39 months The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
Phase Ib: Disease Control Rate (DCR) Approximately 39 months The DCR is defined as the percentage of participants who have a confirmed CR or PR or who have stable disease (SD) after randomization.
Phase Ib: Volrustomig concentration in serum Up to 27 months To assess the serum concentration of volrustomig when administered concomitantly with casdatifan.
Phase Ib: Casdatifan concentration in plasma Up to 27 months To assess the plasma concentration of casdatifan when administered concomitantly with volrustomig.
Phase Ib: Time to Response (TTR) Approximately 39 months The TTR is defined as the time from randomization until the first documentation of a subsequently confirmed objective response.
Phase III: Overall Survival Approximately 67 months The OS is defined as the time from randomization until the date of death due to any cause.
Phase III: Time to second progression or death (PFS2) Approximately 67 months 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.
Phase III: Objective Response rate (ORR) Approximately 67 months The ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR.
Phase III: Duration of Response (DoR) Approximately 67 months 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.
Phase III: Progression-free Survival Approximately 67 months The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
Related Research Topics
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