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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join 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 cannot join 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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

fianlimab. A monoclonal antibody directed against the inhibitory receptor lymphocyte activation gene-3 protein (LAG-3; LAG3; CD223), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, fianlimab binds to LAG-3 expressed by tumor infiltrating lymphocytes (TILs) and blocks LAG-3 binding to tumor cells expressing major histocompatibility complex (MHC) class II molecules. This may activate antigen-specific T lymphocytes and enhance cytotoxic T-lymphocyte (CTL)-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG-3, a member of the immunoglobulin superfamily (IgSF), is expressed on various immune cells; its expression on TILs is associated with tumor-mediated immune suppression and the negative regulation of both cellular proliferation and T-cell activation. NCI Drug Dictionary

cemiplimab-rwlc. A human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1, PCD-1) protein, with potential immune checkpoint inhibitory and antineoplastic activity. Upon administration, cemiplimab-rwlc binds to PD-1, inhibits its binding to the PD-1 ligand programmed cell death-1 ligand 1 (PD-L1), and prevents the activation of its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T cells. PD-1, a transmembrane protein in the immunoglobulin superfamily expressed on activated T cells, negatively regulates T-cell activation and effector function when activated by its ligand; it plays an important role in tumor evasion from host immunity. NCI Drug Dictionary

ipilimumab. A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system. NCI Drug Dictionary

nivolumab. A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• Fianlimab (Drug): Fianlimab will be co-administered by IV.
• Ipilimumab (Drug): Ipilimumab will be administered by IV.
• Nivolumab (Drug): Nivolumab will be administered by IV. Maintenance nivolumab will then be administered by IV.
• Cemiplimab (Drug): Cemiplimab will co-administered by IV.

Randomized · Parallel · masking: None

Main goals

• Objective Response Rate (ORR) (2 years)

Other goals

• Median Progression Free Survival (PFS)
• 12-month Progression Free Survival (PFS)
• 24-month Progression Free Survival (PFS)
• Duration of Response (DOR)
• Treatment Free Survival (TFS)
• Adverse Event Rates

Planned enrollment: 120 (estimated).

• Georgetown University, Washington D.C., District of Columbia
• University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
• Penn State Cancer Institute, Hershey, Pennsylvania
• Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
• Froedtert and The Medical College of Wisconsin, Milwaukee, Wisconsin

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07188896
• NCI Drug Dictionary: C132339
• NCI Drug Dictionary: C121540
• NCI Drug Dictionary: C2654
• NCI Drug Dictionary: C68814

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 3, 2026. Public record; not medical advice.