Clinical trial NCT07000149: A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC
Official title: A Phase Ib/III Randomized, Multicenter, Global Study of Volrustomig Plus Casdatifan or Volrustomig Monotherapy Versus Nivolumab Plus Ipilimumab as First-line Treatment for Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Advanced Clear Cell Renal Cell Carcinoma
Keywords: Programmed cell death-ligand-1
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
First-line treatment (1L)
Immunotherapy
Kidney cancer
Clear cell renal carcinoma
Immuno-oncology bispecific (IO-bispecific)
Volrustomig
Casdatifan
Hypoxia-inducible factor-2α (HIF-2α)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Arcus Biosciences, Inc.
First posted: 2025-06-02
Enrollment: 1116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Phase Ib: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Approximately 39 months
measure: Phase III: Progression-free Survival (PFS)
timeFrame: Approximately 38 months
measure: Phase III: Overall Survival (OS)
timeFrame: Approximately 67 months
Secondary outcomes:
measure: Phase Ib: Objective Response rate (ORR)
timeFrame: Approximately 39 months
measure: Phase Ib: Duration of Response (DoR)
timeFrame: Approximately 39 months
measure: Phase Ib: Progression-free Survival (PFS)
timeFrame: Approximately 39 months
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Approximately 39 months
measure: Phase Ib: Volrustomig concentration in serum
timeFrame: Up to 27 months
measure: Phase Ib: Casdatifan concentration in plasma
timeFrame: Up to 27 months
measure: Phase Ib: Time to Response (TTR)
timeFrame: Approximately 39 months
measure: Phase III: Overall Survival
timeFrame: Approximately 67 months
measure: Phase III: Number of participants with AEs and SAEs
timeFrame: Approximately 67 months
measure: Phase III: Time to second progression or death (PFS2)
timeFrame: Approximately 67 months
measure: Phase III: Objective Response rate (ORR)
timeFrame: Approximately 67 months
measure: Phase III: Duration of Response (DoR)
timeFrame: Approximately 67 months
measure: Phase III: Progression-free Survival
timeFrame: Approximately 67 months
Other outcomes:
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