Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma

NCT07748988 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VICCURO25-03
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-institution, pilot study of oral casdatifan, a selective HIF-2α inhibitor, in patients with metastatic clear cell renal cell carcinoma refractory to prior IO- and VEGF-based therapies. This phase I trial evaluates the effects of casdatifan on certain genes linked to kidney cancer growth and tests it for the treatment of clear cell renal cell cancer that has not responded to previous treatment (refractory) and that has spread from where it first started (primary site) to other places in the body (metastatic). Casdatifan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Refractory Clear Cell Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma

Keywords

HIF-mediated gene expression

Outcome Measures

Primary Outcomes (1)

• To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory ccRCC population.

  A serial biopsy design, incorporating biopsies at baseline, on-treatment, and disease progression, enables longitudinal evaluation of the HIF-2α transcriptional program and characterization of adaptive or resistance-associated gene expression changes emerging during therapy.

  1 year (From baseline to on-treatment biopsy)

Secondary Outcomes (2)

• To assess changes in global tumor gene expression following casdatifan treatment.

  1 year (From baseline to on-treatment biopsy)

• To identify differences in baseline and on-treatment HIF-mediated gene expression between objective responders and non-responders.

  1 year (From baseline to on-treatment biopsy)

Study Arms (1)

Casdatifan

EXPERIMENTAL

Casdatifan will be taken orally at a fixed dose of 100 mg once daily, with or without food, on a continuous schedule beginning on Cycle 1, Day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI, tumor biopsy and blood sample collection throughout the study.

Drug: casdatifan

Interventions

casdatifan DRUG

Casdatifan will be taken orally at a fixed dose of 100 mg once daily, with or without food, on a continuous schedule beginning on Cycle 1, Day 1.

Also known as: AB521, investigational, orally bioavailable small-molecule inhibitor of HIF-2α

Casdatifan

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent.
• Male or female ≥ 18 years of age on the day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Histologically confirmed metastatic clear cell renal cell carcinoma (ccRCC)
• Patients must have received at least one immune oncology (IO) agent and at least one VEGF-targeted therapy (alone or in combination)
• Measurable tumor burden which can be followed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST 1.1 as assessed by the local site investigator
• At least one metastatic lesion that is amenable to percutaneous biopsy
• Adequate organ and bone marrow function resulted ≤ 28 days prior to first dose of protocol-indicated treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL.
• Platelets ≥ 100,000/µL.
• Hemoglobin ≥ 10.0 g/dL or ≥ 6.2 mmol/L.
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants).
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), or direct bilirubin ≤ ULN for participants with total bilirubin \> 1.5 xULN.
• AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional upper limit of normal (ULN)
• Women must not be breastfeeding and further agree to not breastfeed during study treatment; and for at least 7 days after patient's final dose of casdatifan.

You may not qualify if:

• Prior treatment with HIF 2α inhibitors (e.g. belzutifan or related agents)
• Is currently participating in or within 2 weeks prior to receiving first dose of study treatment in a study of an investigational agent or investigational device.
• Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks after the last dose or last exposure to the previous investigational agent or investigational device.
• Known severe hypersensitivity (≥ Grade 3) to any of the excipients of casdatifan.
• History of myocarditis or pericarditis or other known underlying heart disease that is clinically significant by investigator judgment (for example, cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III or IV, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction). History of cerebrovascular accident (including TIA) within the past 6 months (24 weeks) prior to starting study treatment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection/sepsis, interstitial lung disease, recent hospitalizations with unresolved symptoms, poorly controlled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
• Inability to swallow study treatment.
• Contraindications to biopsy (e.g. bleeding diathesis, uncorrectable coagulopathy)

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Brian Rini

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 6, 2026
• Study Start: September 21, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)