A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC (eVOLVE-RCC02)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Advanced Clear Cell Renal Cell Carcinoma

Treatments: Drug: Volrustomig; Drug: Nivolumab; Drug: Ipilimumab; Drug: Casdatifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT07000149

2024-519865-23-00 (Other Identifier)

D798NC00001

Details and patient eligibility

About

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).

Full 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).

Enrollment: 1,116 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,116 participants in 5 patient groups

Arm 1A (Volrustomig Dose 1 + Casdatifan)

Experimental group

Description:

Participants will receive dose 1 of volrustomig in combination with casdatifan.

Treatment:

Drug: Casdatifan

Drug: Volrustomig

Arm 1B (Volrustomig Dose 2 + Casdatifan)

Experimental group

Description:

Participants will receive dose 2 of volrustomig in combination with casdatifan.

Treatment:

Drug: Casdatifan

Drug: Volrustomig

Arm 3A (Volrustomig Dose X + Casdatifan)

Experimental group

Description:

Participants will receive Volrustomig at the dose to be determined in the Phase Ib part of the study, in combination with casdatifan.

Treatment:

Drug: Casdatifan

Drug: Volrustomig

Arm 3B (Volrustomig Dose 1)

Experimental group

Description:

Participants will receive dose 1 of volrustomig.

Treatment:

Drug: Volrustomig

Arm 3C (Nivolumab + Ipilimumab)

Active Comparator group

Description:

Participants will receive nivolumab plus ipilimumab as standard of care treatment.

Treatment:

Drug: Ipilimumab

Drug: Nivolumab