Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
A Randomized, Double-Blind, Active-Control, Multicenter Phase 3 Trial of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
2 other identifiers
interventional
720
16 countries
159
Brief Summary
The purpose of the study is to evaluate the progression-free survival (PFS) of casdatifan versus placebo when each is given in combination with cabozantinib in adult patients with confirmed advanced or metastatic clear cell Renal Cell Carcinoma who have experienced progression on or after prior anti-PD-1 or anti-PD-L1 immunotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2025
Longer than P75 for phase_3
159 active sites
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
First Submitted
Initial submission to the registry
June 2, 2025
CompletedFirst Posted
Study publicly available on registry
June 10, 2025
CompletedStudy Start
First participant enrolled
September 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
July 31, 2026
April 1, 2026
2.6 years
June 2, 2025
July 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
up to approximately 33 months
Secondary Outcomes (6)
Overall Survival (OS)
up to approximately 64 months
Objective Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
up to approximately 33 months
Duration of Response (DOR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
up to approximately 33 months
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR)
up to approximately 33 months
The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
up to approximately 33 months
- +1 more secondary outcomes
Study Arms (2)
Arm A (Experimental Arm)
EXPERIMENTALCasdatifan and cabozantinib taken orally
Arm B (Comparator Arm)
PLACEBO COMPARATORPlacebo and cabozantinib taken orally
Interventions
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Eligibility Criteria
You may qualify if:
- Unresectable and measurable locally advanced or metastatic renal cell carcinoma with a primary clear cell component.
- A Karnofsky Performance Status (KPS) score ≥ 80%
- At least 1 target lesion measurable by computed tomography/magnetic resonance imaging per RECIST 1.1, not within a field of prior radiation therapy.
- Adequate organ and marrow function, ≤ 1 week prior to randomization.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test.
You may not qualify if:
- Received prior treatment with a HIF-2α inhibitor or cabozantinib.
- Other prior malignancy active within the previous year except for locally curable cancers that have been apparently cured.
- Ongoing clinically significant toxicities related to any prior anticancer treatment, or toxicities Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) regardless of relatedness to prior anticancer therapies.
- Uncontrolled or poorly controlled hypertension, defined as a sustained blood pressure \> 150 mmHg systolic or \> 90 mmHg diastolic despite optimal antihypertensive treatment.
- History of leptomeningeal disease or spinal cord compression.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (159)
Research Site
Gilbert, Arizona, 85234, United States
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Goodyear, Arizona, 85338, United States
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Phoenix, Arizona, 85054, United States
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Duarte, California, 91010, United States
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Irvine, California, 91304, United States
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La Jolla, California, 92103, United States
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Los Angeles, California, 90095, United States
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Sacramento, California, 95817, United States
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San Diego, California, 92103, United States
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New Haven, Connecticut, 06519, United States
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Washington D.C., District of Columbia, 20057, United States
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Jacksonville, Florida, 32224, United States
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Miami, Florida, 33136, United States
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Orlando, Florida, 32804, United States
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Atlanta, Georgia, 30318, United States
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Atlanta, Georgia, 30322, United States
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Newnan, Georgia, 30265, United States
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Zion, Illinois, 60099, United States
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Indianapolis, Indiana, 46202, United States
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Louisville, Kentucky, 40207, United States
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Jefferson, Louisiana, 70121, United States
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Baltimore, Maryland, 21287, United States
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Boston, Massachusetts, 02114, United States
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Boston, Massachusetts, 02215, United States
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Rochester, Minnesota, 55905, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68198, United States
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New Brunswick, New Jersey, 08903, United States
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Buffalo, New York, 14263, United States
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New York, New York, 10461, United States
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Rochester, New York, 14642, United States
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Chapel Hill, North Carolina, 27514, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44106, United States
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Portland, Oregon, 97212, United States
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Monroeville, Pennsylvania, 15146, United States
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Charleston, South Carolina, 29425, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75390, United States
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Lubbock, Texas, 79430, United States
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Salt Lake City, Utah, 84112, United States
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Charlottesville, Virginia, 22903, United States
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Seattle, Washington, 98109, United States
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Buenos Aires, Argentina
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Box Hill, Australia
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Chermside, Australia
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Elizabeth Vale, Australia
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Frankston, Australia
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Frenchs Forest, Australia
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Heidelberg, Australia
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Hobart, Australia
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Kurralta Park, Australia
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Macquarie Park, Australia
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Saint Leonards, Australia
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Subiaco, Australia
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Westmead, Australia
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Calgary, Canada
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Edmonton, Canada
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Hamilton, Canada
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Montreal, Canada
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Sherbrooke, Canada
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Toronto, Canada
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Vancouver, Canada
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Brno, Czechia
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Brno-střed, Czechia
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Hradec, Czechia
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Prague, Czechia
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Angers, France
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Brest, France
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Caen, France
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Clermont-Ferrand, France
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Lille, France
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Marseille, France
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Montpellier, France
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Paris, France
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Pessac, France
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Poitiers, France
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Reims, France
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Rennes, France
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Strasbourg, France
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Toulouse, France
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Villejuif, France
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Berlin, Germany
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Dresden, Germany
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Essen, Germany
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Frankfurt, Germany
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Freiburg im Breisgau, Germany
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Halle, Germany
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Hanover, Germany
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Heidelberg, Germany
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Leipzig, Germany
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Lübeck, Germany
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Marburg, Germany
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Rostock, Germany
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Ulm, Germany
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Milan, Italy
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Naples, Italy
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Rome, Italy
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Terni, Italy
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Verona, Italy
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Akita, Japan
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Asahikawa, Japan
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Fukuoka, Japan
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Kobe, Japan
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Matsuyama, Japan
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Nankoku, Japan
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Osaka, Japan
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Sapporo, Japan
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Shinjuku, Japan
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Yokohama, Japan
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Amsterdam, Netherlands
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Maastricht, Netherlands
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Nijmegen, Netherlands
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Rotterdam, Netherlands
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Utrecht, Netherlands
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Zwolle, Netherlands
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Auckland, New Zealand
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Christchurch, New Zealand
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Hamilton, New Zealand
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Rotorua, New Zealand
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Krakow, Poland
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Otwock, Poland
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Poznan, Poland
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Rzeszów, Poland
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Skorzewo, Poland
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Tomaszów Mazowiecki, Poland
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Wroclaw, Poland
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Bucharest, Romania
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Craiova, Romania
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Iași, Romania
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Suceava, Romania
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Timișoara, Romania
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Busan, South Korea
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Daejeon, South Korea
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Goyang, South Korea
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Seongnam, South Korea
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Seoul, South Korea
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Suwon, South Korea
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Barcelona, Spain
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Córdoba, Spain
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Madrid, Spain
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Málaga, Spain
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Santander, Spain
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Seville, Spain
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Vigo, Spain
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Cambridge, United Kingdom
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Cottingham, United Kingdom
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Exeter, United Kingdom
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Glasgow, United Kingdom
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Leeds, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Newcastle upon Tyne, United Kingdom
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Northwood, United Kingdom
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Preston, United Kingdom
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Southampton, United Kingdom
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Sutton, United Kingdom
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Truro, United Kingdom
Related Publications (1)
Mailyan AK, Mata G, Beatty JW, Drew SL, Fournier J, Yu K, Gal B, Kalisiak J, Yan X, Tran A, Su Y, Rosen BR, Jeffrey JL, Hardman C, Epplin M, Ginn E, Sun M, Chen A, Fabila P, Sivick KE, Schweickert PG, Piovesan D, Meleza C, Pham AT, Chen PY, Jin L, Walters MJ, Walker NP, Kwon HJ, Leleti MR, Powers JP, Lawson KV. Discovery of Casdatifan, Part II: A Potent and Orally Bioavailable Inhibitor of Hypoxia Inducible Factor-2alpha. J Med Chem. 2026 Jun 25;69(12):14952-14988. doi: 10.1021/acs.jmedchem.5c03724. Epub 2026 Jun 5.
PMID: 42246926DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Arcus Biosciences
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 2, 2025
First Posted
June 10, 2025
Study Start
September 8, 2025
Primary Completion (Estimated)
April 1, 2028
Study Completion (Estimated)
December 1, 2030
Last Updated
July 31, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan \[SAP\], Clinical Study Report \[CSR\]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.