Inclusion Criteria:
* Documented informed consent of the participant and/or legally authorized representative
* Assent, when appropriate, will be obtained per institutional guidelines
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies
* If unavailable, exceptions may be granted with study principle investigator (PI) approval
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Age ≥ 18 years
* Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component or sarcomatoid component
* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) renal cell carcinoma with intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria
* No prior systemic therapy for renal cell carcinoma (RCC) with the following exception:
* One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
* Absolute neutrophil count (ANC) ≥ 1500/uL without granulocyte colony-stimulating factor support
* White blood cell count ≥ 2500/uL
* Platelets ≥ 100,000/uL without transfusion
* Hemoglobin ≥ 8 g/dL
* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases
* Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)
* Serum albumin ≥ 2.8 g/dl
* Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN
* Serum calculated creatinine clearance ≥ 50mL/min using the Cockcroft-Gault equation
* Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab for women with childbearing potential, and 7 months after the last dose of nivolumab for men
* Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause).
* Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site
Exclusion Criteria:
* Prior treatment with ipilimumab and/or nivolumab
* Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
* Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
* Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
* Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
* Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed
* Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* Malabsorption syndrome
* Uncompensated/symptomatic hypothyroidism
* Moderate to severe hepatic impairment (Child-Pugh B or C)
* Requirement for hemodialysis or peritoneal dialysis
* History of solid organ or allogenic stem cell transplant
* Other clinically significant disorders that would preclude safe study participation
* Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions:
* Type 1 diabetes mellitus
* Hypothyroidism only requiring hormone replacement
* Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
* Conditions not expected to recur in the absence of an external trigger
* Pregnant or lactating females
* Inability to swallow tablets/capsules or unwillingness or inability to receive IV administration
* Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
* Exclusion of subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
* Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Moderate burden on patient
