Refractory Clear Cell Renal Cell CarcinomaPhase 1NCT07748988
Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma
A Phase 1 study testing casdatifan in people with Refractory Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Refractory Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma
- What is being tested?
- casdatifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Sep 2026to 1 Jan 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 23Show fewer
- 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.
- A woman of childbearing potential (WOCBP) - see Appendix 3 for definition of WOCBP - must have a negative serum or urine pregnancy test during screening within 28 days prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception (Appendix 3) from the time of signing consent, and until at least 7 days after her final dose of casdatifan.
- Men must refrain from donating sperm for at least 7 days after patient's final dose of casdatifan.
- A man able to father children (see Appendix 3 for definition) who is sexually active with a WOCBP must agree to follow instructions for using acceptable contraception (Appendix 3), from the time of signing consent, and until at least 7 days after his final dose of casdatifan.
- No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry ≤ 88%.
- No active pneumonitis at screening as assessed by CT scan.
- No medical history of severe chronic obstructive pulmonary disease (COPD).
- If a participant has CNS metastases the participant must meet the following criteria:
- Participants with previously treated brain metastases may participate provided they are clinically stable and without steroid treatment for at least 14 days prior to the first dose of study treatment. Participants with carcinomatous meningitis are excluded.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Vanderbilt-Ingram Service for Timely Access, 800-811-8480, cip@vumc.org
Brian I Rini, MD
About this study
Official title: A Pilot Study of HIF-Mediated Gene Expression Changes in Casdatifan-Treated Refractory Renal Cell Carcinoma
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory clear cell renal cell carcinoma (ccRCC) population.
SECONDARY OBJECTIVES:
- To assess changes in global tumor gene expression following casdatifan treatment.
II. To identify differences in baseline and on-treatment HIF-mediated gene expression between objective responders and non-responders.
OUTLINE:
Patients receive casdatifan orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study.
Two dose reductions will be permitted in the event of drug-related adverse events, per protocol-defined criteria:
- Reduced dose (-1): 50mg once daily
- Reduced dose (-2): 25mg once daily Treatment will be discontinued if toxicity is not manageable at this reduced dose.
After completion of study treatment, patients who discontinue treatment for reasons other than disease progression are followed up every 12 weeks thereafter.
Casdatifan will be provided by Arcus. No additional therapeutic agents will be administered as part of this protocol.
- Being tested
- casdatifan
- Keywords
- HIF-mediated gene expression
- Medical subject headings
- Carcinoma, Renal Cell, Clear-cell metastatic renal cell carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
casdatifanDrug
Also called AB521, investigational, orally bioavailable small-molecule inhibitor of HIF-2α
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: casdatifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year (From baseline to on-treatment biopsy)
Secondary outcomes (2)
To assess changes in global tumor gene expression following casdatifan treatment.
Differential expression of genome-wide transcripts between baseline and on-treatment biopsies.
Measured: 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.
Comparison of RNA expression profiles stratified by best overall response per RECIST v1.1
Measured: 1 year (From baseline to on-treatment biopsy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study start21 Sep 2026
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Arcus Biosciences, Inc.
- Responsible party
- Principal investigator, Brian Rini, Vanderbilt-Ingram Cancer Center
- Investigators
- Brian Rini, Principal investigator, Vanderbilt University/Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07748988
- Sponsor's protocol ID
- VICCURO25-03
- Status last verified
- Sep 2026
- First submitted
- 28 Jul 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of HIF-Mediated Gene Expression Changes in Casdatifan-Treated Refractory Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07748988
- Acronym / sponsor ID
- VICCURO25-03
- Keywords
- HIF-mediated gene expression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- Arcus Biosciences, Inc.
- Study start
- 21 Sep 2026 (actual)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 6 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory clear cell renal cell carcinoma (ccRCC) population.
SECONDARY OBJECTIVES:
- To assess changes in global tumor gene expression following casdatifan treatment.
II. To identify differences in baseline and on-treatment HIF-mediated gene expression between objective responders and non-responders.
OUTLINE:
Patients receive casdatifan orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study.
Two dose reductions will be permitted in the event of drug-related adverse events, per protocol-defined criteria:
- Reduced dose (-1): 50mg once daily
- Reduced dose (-2): 25mg once daily Treatment will be discontinued if toxicity is not manageable at this reduced dose.
After completion of study treatment, patients who discontinue treatment for reasons other than disease progression are followed up every 12 weeks thereafter.
Casdatifan will be provided by Arcus. No additional therapeutic agents will be administered as part of this protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Casdatifan | Experimental | Drug: casdatifanCasdatifan 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| casdatifanAlso: AB521, investigational, orally bioavailable small-molecule inhibitor of HIF-2αCasdatifan 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. | Drug | Casdatifan |
Primary outcome
To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory ccRCC population.
Time frame: 1 year (From baseline to on-treatment biopsy)
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.
2 secondary outcomes
To assess changes in global tumor gene expression following casdatifan treatment.
Time frame: 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.
Time frame: 1 year (From baseline to on-treatment biopsy)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Rini principal investigator
Vanderbilt University/Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing casdatifan in people with Refractory Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory ccRCC population. (time frame: 1 year (From baseline to on-treatment biopsy)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.