A Randomized Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC)

NCT07188896 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU23-651
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Renal Cell Carcinoma (aRCC); Metastatic Renal Cell Carcinoma ( mRCC); Clear Cell Renal Cell Carcinoma (ccRCC)

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (6)

• Median Progression Free Survival (PFS)

  5 years

• 12-month Progression Free Survival (PFS)

  12 months

• 24-month Progression Free Survival (PFS)

  24 months

• Duration of Response (DOR)

  5 years

• Treatment Free Survival (TFS)

  5 years

Study Arms (3)

Arm A: Cemiplimab, Fianlimab, and Ipilimumab

EXPERIMENTAL

Cemiplimab and fianlimab will be co-administered by IV. Ipilimumab will be administered by IV.

Drug: Fianlimab; Drug: Ipilimumab; Drug: Cemiplimab

Arm B: Cemiplimab and Fianlimab

EXPERIMENTAL

Cemiplimab and fianlimab will be co-administered by IV.

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.

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Fianlimab DRUG

Fianlimab will be co-administered by IV.

Arm A: Cemiplimab, Fianlimab, and Ipilimumab; Arm B: Cemiplimab and Fianlimab

Ipilimumab DRUG

Ipilimumab will be administered by IV.

Also known as: Yervoy

Arm A: Cemiplimab, Fianlimab, and Ipilimumab; Arm C: Nivolumab and Ipilimumab

Nivolumab DRUG

Nivolumab will be administered by IV. Maintenance nivolumab will then be administered by IV.

Also known as: Opdivo

Arm C: Nivolumab and Ipilimumab

Cemiplimab DRUG

Cemiplimab will co-administered by IV.

Arm A: Cemiplimab, Fianlimab, and Ipilimumab; Arm B: Cemiplimab and Fianlimab

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Brian Rini: lead
• Vanderbilt-Ingram Cancer Center: collaborator
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Ipilimumab; Nivolumab; cemiplimab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Brian Rini, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Rini, MD

CONTACT

615-936-8422; brian.rini@vumc.org

Allison Lipps

CONTACT

317-634-5842; alipps@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: September 23, 2025
• Study Start: April 29, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (1)