RecruitingInterventionalPhase 3

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

NCT ID: NCT07011719Sponsor: Arcus Biosciences, Inc.Last updated: 2026-06-02

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.

Arms & interventions

DrugCasdatifan
Administered as specified in the treatment arm
DrugCabozantinib
Administered as specified in the treatment arm
DrugPlacebo
Administered as specified in the treatment arm

Outcome measures

Primary

Progression-free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
Time frame: up to approximately 33 months

Secondary

Overall Survival (OS)
Time frame: up to approximately 64 months
Objective Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
Time frame: up to approximately 33 months
Duration of Response (DOR) as assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1
Time frame: up to approximately 33 months
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR)
Time frame: up to approximately 33 months
The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
Time frame: up to approximately 33 months
Time to first symptom deterioration in National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (NFKSI-DRS) Items 1-9 sub-scale score.
Time frame: up to approximately 33 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * 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. Exclusion Criteria: * 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. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study locations (40)

Research Site

Gilbert, Arizona, 85234

Recruiting

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Goodyear, Arizona, 85338

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Phoenix, Arizona, 85054

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Duarte, California, 91010

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La Jolla, California, 92103

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Los Angeles, California, 90095

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Sacramento, California, 95817

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San Diego, California, 92103

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New Haven, Connecticut, 06519

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Jacksonville, Florida, 32224

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Miami, Florida, 33136

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Orlando, Florida, 32804

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Atlanta, Georgia, 30318

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Atlanta, Georgia, 30322

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Newnan, Georgia, 30265

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Zion, Illinois, 60099

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Indianapolis, Indiana, 46202

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Louisville, Kentucky, 40207

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Jefferson, Louisiana, 70121

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Baltimore, Maryland, 21287

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Boston, Massachusetts, 02114

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Boston, Massachusetts, 02215

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Rochester, Minnesota, 55905

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St Louis, Missouri, 63110

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Omaha, Nebraska, 68198

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New Brunswick, New Jersey, 08903

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Buffalo, New York, 14263

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Rochester, New York, 14642

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Chapel Hill, North Carolina, 27514

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Cleveland, Ohio, 44106

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Portland, Oregon, 97212

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Monroeville, Pennsylvania, 15146

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Charleston, South Carolina, 29425

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Nashville, Tennessee, 37203

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Nashville, Tennessee, 37232

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Dallas, Texas, 75390

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Lubbock, Texas, 79430

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Salt Lake City, Utah, 84112

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Charlottesville, Virginia, 22903

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Seattle, Washington, 98109

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References

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 5. doi: 10.1021/acs.jmedchem.5c03724. Online ahead of print.(PubMed)