A Randomized Phase 2 Trial of Fianlimab and Cemiplimab +/- Ipilimumab or Ipilimumab Plus Nivolumab in First-line Advanced Renal Cell Carcinoma (RCC)

Inclusion Criteria: 1. 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. 2. Age ≥ 18 years at the time of consent. 3. Karnofsky Performance Status ≥ 70% within 14 days prior to registration. 4. Histological or cytological evidence of renal cell carcinoma having a clear cell component 5. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV \[version 9\]) renal cell carcinoma. 6. Treatment naïve for systemic therapy for renal cell carcinoma including no prior neo/adjuvant systemic therapy 7. Measurable disease according to RECIST 1.1 within 28 days prior to registration. 8. 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. 9. Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration. 10. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. 11. 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. 12. 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 13. 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. 14. 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. 15. 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. Exclusion Criteria: 1. Prior systemic therapy against renal cell carcinoma in the neo/adjuvant or metastatic setting 2. Any condition requiring ongoing ≥ 10 mg prednisone equivalent/day 3. Participants with a history of myocarditis. 4. 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. 5. 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. 6. Central nervous system (CNS) metastases as described in the protocol. 7. Active infection requiring systemic therapy as described in the protocol. 8. Pregnant or breastfeeding as described in the protocol. 9. 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. 10. 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. 11. Known hypersensitivity to the active substances or to any of the excipients. 12. 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.