Advanced Renal Cell Carcinoma (aRCC)Phase 2NCT07188896
A Randomized Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC)
A Phase 2 study testing Fianlimab, Ipilimumab and Nivolumab in people with Advanced Renal Cell Carcinoma (aRCC) and Metastatic Renal Cell Carcinoma ( mRCC), run by Brian Rini at 5 sites in United States.
Trial summary
This three-arm randomized phase 2 trial will enroll advanced clear cell RCC patients (all IMDC risk groups). Patients will be randomized 2:2:1 to either Arm A (fianlimab/ cemiplimab/ ipilimumab), Arm B (fianlimab/ cemiplimab), or Arm C (standard ipilimumab/ nivolumab), respectively. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Renal Cell Carcinoma (aRCC), Metastatic Renal Cell Carcinoma ( mRCC), Clear Cell Renal Cell Carcinoma (ccRCC)
- What is being tested?
- Fianlimab, Ipilimumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 5 sitesUnited States
- Study dates
- 29 Apr 2026to 30 Nov 2030
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status ≥ 70% within 14 days prior to registration.
- Histological or cytological evidence of renal cell carcinoma having a clear cell component
- Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV [version 9]) renal cell carcinoma.
- Treatment naïve for systemic therapy for renal cell carcinoma including no prior neo/adjuvant systemic therapy
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- Measurable disease according to RECIST 1.1 within 28 days prior to registration.
- Patient must have either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, obtained from preferably a metastatic lesion, preferably within 3 months or no more than 12 months with an associated pathology report. If the metastatic lesion biopsy specimen does not contain at least 20 unstained slides, supplementation with primary kidney cancer tissue is acceptable.
- Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
- Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration.
- Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or must use an effective method(s) of contraception. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception.
- Known HIV-infected subjects on effective anti-retroviral therapy with undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen within 6 months of registration are eligible for this trial. Testing is not required at screening unless mandated by local policy
- Subjects with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load (serum hepatitis B virus DNA PCR that is below the limit of detection) and be on suppressive therapy, if indicated.
- Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy). For subjects with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Testing is not required at screening unless mandated by local policy.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Who cannot join
- Prior systemic therapy against renal cell carcinoma in the neo/adjuvant or metastatic setting
- Any condition requiring ongoing ≥ 10 mg prednisone equivalent/day
- Participants with a history of myocarditis.
- If clinically indicated based on clinical assessment and any ECG abnormalities, optional troponin T (TnT) or troponin I (TnI) may be done as described in the protocol.
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are allowed: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
- Central nervous system (CNS) metastases as described in the protocol.
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- Active infection requiring systemic therapy as described in the protocol.
- Pregnant or breastfeeding as described in the protocol.
- Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion.
- Subjects must not receive live attenuated vaccines within 4 weeks prior to Cycle 1 Day 1 or at any time during the study. Inactivated vaccines are allowed.
- Known hypersensitivity to the active substances or to any of the excipients.
- Currently participating in another study or participated in any study of an investigational agent or investigational device within 30 days of the first dose of study drug.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Kate Ashcraft, PhD, 919-966-0807, kate_ashcraft@med.unc.edu
Catherine Fahey, MD, PhD
- Recruiting
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Meredith Belga, RN, 717-531-5232, mbelga@pennstatehealth.psu.edu
Stuthi Perimbeti, MBBS, MPH
- Recruiting
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Jaime Goeldner, 414-805-8943, jgoeldner@mcw.edu
Deepak Kilari, MD
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Rebekah Caza, RN, MSN, 615-343-6584, rebekah.caza@vumc.org
Brian Rini, MD
- Recruiting
Georgetown University
Washington D.C., District of Columbia, 20057
Jamie Manganti, BSN, RN, 202-687-3937, jm3821@georgetown.edu
Michael Atkins, MD
About this study
Official title: A Randomized Phase 2 Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC)
This three-arm randomized phase 2 trial will enroll advanced clear cell RCC patients (all IMDC risk groups). Patients will be randomized 2:2:1 to either Arm A (fianlimab/ cemiplimab/ ipilimumab), Arm B (fianlimab/ cemiplimab), or Arm C (standard ipilimumab/ nivolumab), respectively.
- Conditions
- Advanced Renal Cell Carcinoma (aRCC), Metastatic Renal Cell Carcinoma ( mRCC), Clear Cell Renal Cell Carcinoma (ccRCC)
- Being tested
- Fianlimab, Ipilimumab, Nivolumab, Cemiplimab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FianlimabDrug
Fianlimab will be co-administered by IV.
IpilimumabDrug
Also called Yervoy
Ipilimumab will be administered by IV.
NivolumabDrug
Also called Opdivo
Nivolumab will be administered by IV. Maintenance nivolumab will then be administered by IV.
CemiplimabDrug
Cemiplimab will co-administered by IV.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Cemiplimab, Fianlimab, and Ipilimumab | Experimental | Cemiplimab and fianlimab will be co-administered by IV. Ipilimumab will be administered by IV. Receives: Drug: Fianlimab; Drug: Ipilimumab; Drug: Cemiplimab |
| Arm B: Cemiplimab and Fianlimab | Experimental | Cemiplimab and fianlimab will be co-administered by IV. Receives: Drug: Fianlimab; Drug: Cemiplimab |
| Arm C: Nivolumab and Ipilimumab | Active comparator | Nivolumab and ipilimumab will be by IV. Nivolumab will be administered by IV after the combination. Receives: Drug: Ipilimumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR is defined as confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST 1.1.
Measured: 2 years
Secondary outcomes (6)
Median Progression Free Survival (PFS)
PFS is defined as the time from Day 1 of treatment to the first documented disease progression per RECIST 1.1, clinically progressive disease per investigator, or death due to any cause, whichever occurs first.
Measured: 5 years
12-month Progression Free Survival (PFS)
PFS is defined as the time from Day 1 of treatment to the first documented disease progression per RECIST 1.1, clinically progressive disease per investigator, or death due to any cause, whichever occurs first.
Measured: 12 months
24-month Progression Free Survival (PFS)
PFS is defined as the time from Day 1 of treatment to the first documented disease progression per RECIST 1.1, clinically progressive disease per investigator, or death due to any cause, whichever occurs first.
Measured: 24 months
Duration of Response (DOR)
DOR is defined as the time from first documented evidence of CR or PR per RECIST 1.1 until disease progression based on RECIST 1.1 or death due to any cause, whichever occurs first.
Measured: 5 years
Treatment Free Survival (TFS)
TFS will be assessed based on the area between two time to event KM curves from the time of study treatment initiation to study treatment discontinuation and from study initiation to initiation of subsequent systemic anti-cancer treatment or death. Time on or off treatment with Grade 3 or greater treatment related toxicities per CTCAE v5 will be determined as the area between study initiation and toxicity start and study initiation and Grade 3 toxicity ending.
Measured: 5 years
Adverse Event Rates
The frequency of subjects experiencing treatment related adverse events and SAEs graded per NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start29 Apr 2026
- Primary completion30 Nov 2029 (estimated)
- Study completion30 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Renal Cell Carcinoma (aRCC)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brian Rini
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals, Vanderbilt-Ingram Cancer Center
- Responsible party
- Sponsor-investigator, Brian Rini, Hoosier Cancer Research Network
- Investigators
- Brian Rini, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07188896
- Sponsor's protocol ID
- HCRN GU23-651
- Status last verified
- Sep 2026
- First submitted
- 16 Sep 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT07188896
- Acronym / sponsor ID
- HCRN GU23-651
- Conditions
- Advanced Renal Cell Carcinoma (aRCC), Metastatic Renal Cell Carcinoma ( mRCC), Clear Cell Renal Cell Carcinoma (ccRCC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Brian RiniUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals, Vanderbilt-Ingram Cancer Center
- Study start
- 29 Apr 2026 (actual)
- Primary completion
- 30 Nov 2029 (estimated)
- Study completion
- 30 Nov 2030 (estimated)
- First posted
- 23 Sep 2025 (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 three-arm randomized phase 2 trial will enroll advanced clear cell RCC patients (all IMDC risk groups). Patients will be randomized 2:2:1 to either Arm A (fianlimab/ cemiplimab/ ipilimumab), Arm B (fianlimab/ cemiplimab), or Arm C (standard ipilimumab/ nivolumab), respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Cemiplimab, Fianlimab, and Ipilimumab | Experimental | Drug: Fianlimab, Drug: Ipilimumab, Drug: CemiplimabCemiplimab and fianlimab will be co-administered by IV. Ipilimumab will be administered by IV. |
| Arm B: Cemiplimab and Fianlimab | Experimental | Drug: Fianlimab, Drug: CemiplimabCemiplimab and fianlimab will be co-administered by IV. |
| Arm C: Nivolumab and Ipilimumab | Active comparator | Drug: Ipilimumab, Drug: NivolumabNivolumab and ipilimumab will be by IV. Nivolumab will be administered by IV after the combination. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status ≥ 70% within 14 days prior to registration.
- Histological or cytological evidence of renal cell carcinoma having a clear cell component
- Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV [version 9]) renal cell carcinoma.
Key exclusion criteria (12 listed)
- Prior systemic therapy against renal cell carcinoma in the neo/adjuvant or metastatic setting
- Any condition requiring ongoing ≥ 10 mg prednisone equivalent/day
- Participants with a history of myocarditis.
- If clinically indicated based on clinical assessment and any ECG abnormalities, optional troponin T (TnT) or troponin I (TnI) may be done as described in the protocol.
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are allowed: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
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 |
|---|---|---|
| FianlimabFianlimab will be co-administered by IV. | Drug | Arm A: Cemiplimab, Fianlimab, and Ipilimumab, Arm B: Cemiplimab and Fianlimab |
| IpilimumabAlso: YervoyIpilimumab will be administered by IV. | Drug | Arm A: Cemiplimab, Fianlimab, and Ipilimumab, Arm C: Nivolumab and Ipilimumab |
| NivolumabAlso: OpdivoNivolumab will be administered by IV. Maintenance nivolumab will then be administered by IV. | Drug | Arm C: Nivolumab and Ipilimumab |
| CemiplimabCemiplimab will co-administered by IV. | Drug | Arm A: Cemiplimab, Fianlimab, and Ipilimumab, Arm B: Cemiplimab and Fianlimab |
Primary outcome
Objective Response Rate (ORR)
Time frame: 2 years
ORR is defined as confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST 1.1.
6 secondary outcomes
Median Progression Free Survival (PFS)
Time frame: 5 years
12-month Progression Free Survival (PFS)
Time frame: 12 months
24-month Progression Free Survival (PFS)
Time frame: 24 months
Duration of Response (DOR)
Time frame: 5 years
Treatment Free Survival (TFS)
Time frame: 5 years
Adverse Event Rates
Time frame: 5 years
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 4 Sep 2026.
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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, MD principal investigator
Vanderbilt-Ingram Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fianlimab, Ipilimumab and Nivolumab in people with Advanced Renal Cell Carcinoma (aRCC) and Metastatic Renal Cell Carcinoma ( mRCC), run by Brian Rini at 5 sites 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 15 inclusion and 12 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 4 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 5 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Brian Rini, MD (615-936-8422, brian.rini@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 2 years). 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 4 Sep 2026.