NCT07000149

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).

Trial Health

82
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,116

participants targeted

Target at P75+ for phase_3

Timeline
76mo left

Started Jul 2025

Longer than P75 for phase_3

Geographic Reach
6 countries

32 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress11%
Jul 2025Jul 2032

First Submitted

Initial submission to the registry

May 23, 2025

Completed
10 days until next milestone

First Posted

Study publicly available on registry

June 2, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

July 28, 2025

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 21, 2030

Expected
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 29, 2032

Last Updated

March 10, 2026

Status Verified

March 1, 2026

Enrollment Period

4.6 years

First QC Date

May 23, 2025

Last Update Submit

March 9, 2026

Conditions

Keywords

Programmed cell death-ligand-1Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)First-line treatment (1L)ImmunotherapyKidney cancerClear cell renal carcinomaImmuno-oncology bispecific (IO-bispecific)VolrustomigCasdatifanHypoxia-inducible factor-2α (HIF-2α)

Outcome Measures

Primary Outcomes (3)

  • 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.

    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).

    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.

    Approximately 67 months

Secondary Outcomes (13)

  • Phase Ib: Objective Response rate (ORR)

    Approximately 39 months

  • Phase Ib: Duration of Response (DoR)

    Approximately 39 months

  • Phase Ib: Progression-free Survival (PFS)

    Approximately 39 months

  • Phase Ib: Disease Control Rate (DCR)

    Approximately 39 months

  • Phase Ib: Volrustomig concentration in serum

    Up to 27 months

  • +8 more secondary outcomes

Study Arms (5)

Arm 1A (Volrustomig Dose 1 + Casdatifan)

EXPERIMENTAL

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

Drug: VolrustomigDrug: Casdatifan

Arm 1B (Volrustomig Dose 2 + Casdatifan)

EXPERIMENTAL

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

Drug: VolrustomigDrug: Casdatifan

Arm 3A (Volrustomig Dose X + Casdatifan)

EXPERIMENTAL

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

Drug: VolrustomigDrug: Casdatifan

Arm 3B (Volrustomig Dose 1)

EXPERIMENTAL

Participants will receive dose 1 of volrustomig.

Drug: Volrustomig

Arm 3C (Nivolumab + Ipilimumab)

ACTIVE COMPARATOR

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

Drug: NivolumabDrug: Ipilimumab

Interventions

Volrustomig will be administered as an intravenous (IV) infusion.

Also known as: MEDI5752
Arm 1A (Volrustomig Dose 1 + Casdatifan)Arm 1B (Volrustomig Dose 2 + Casdatifan)Arm 3A (Volrustomig Dose X + Casdatifan)Arm 3B (Volrustomig Dose 1)

Casdatifan will be administered orally.

Also known as: AB521
Arm 1A (Volrustomig Dose 1 + Casdatifan)Arm 1B (Volrustomig Dose 2 + Casdatifan)Arm 3A (Volrustomig Dose X + Casdatifan)

Nivolumab will be administered as an IV infusion.

Also known as: Opdivo
Arm 3C (Nivolumab + Ipilimumab)

Ipilimumab will be administered as an IV infusion.

Also known as: Yervoy
Arm 3C (Nivolumab + Ipilimumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (32)

Research Site

La Jolla, California, 92037, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Nashville, Tennessee, 37232, United States

Location

Research Site

Lubbock, Texas, 79430, United States

Location

Research Site

East Melbourne, 3002, Australia

Location

Research Site

Elizabeth Vale, 5112, Australia

Location

Research Site

North Adelaide, 5000, Australia

Location

Research Site

Syndey, 4032, Australia

Location

Research Site

Beijing, 100142, China

Location

Research Site

Guangzhou, 510060, China

Location

Research Site

Nanjing, 2100008, China

Location

Research Site

Nanning, 530021, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Xiamen, 361003, China

Location

Research Site

Batumi, 6010, Georgia

Location

Research Site

Tbilisi, 0112, Georgia

Location

Research Site

Tbilisi, 0114, Georgia

Location

Research Site

Tbilisi, 0186, Georgia

Location

Research Site

Busan, 48108, South Korea

Location

Research Site

Seongnam-si, 13496, South Korea

Location

Research Site

Seongnam-si, 13620, South Korea

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 06591, South Korea

Location

Research Site

Seoul, 5505, South Korea

Location

Research Site

Kaohsiung City, 833401, Taiwan

Location

Research Site

Taichung, 404327, Taiwan

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Tainan, 704, Taiwan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12Kidney NeoplasmsCarcinoma, Renal Cell

Interventions

NivolumabIpilimumab

Condition Hierarchy (Ancestors)

Urologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 23, 2025

First Posted

June 2, 2025

Study Start

July 28, 2025

Primary Completion (Estimated)

February 21, 2030

Study Completion (Estimated)

July 29, 2032

Last Updated

March 10, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations