CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer

Prior treatment

• Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to \> 10 mg/day of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated
  • Not recovered to =\< grade 1 toxicities related to any prior therapy before administration of study drug
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Not recovered to =\< grade 1 toxicities related to any prior therapy before administration of study drug
• 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

Other illness

• Favorable risk disease by IMDC classification
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Uncontrolled adrenal insufficiency
• 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

Lab values

• White blood cells (WBC) \< 2,000/mm\^3
• Neutrophils \< 1,500/mm\^3
• Platelets \< 100,000/mm\^3
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN) (\> 5 x ULN if liver metastases are present)
• Total bilirubin \> 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin 3.0 mg/dL)
• Calculated creatinine clearance \< 30 millimeters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine \> 1.5 x upper limit of normal (ULN)

Other

• Baseline pulse oximetry less than 92% "on room air"
• Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during the period of treatment
• Women who are pregnant or breastfeeding

• Be willing and able to provide informed consent for the trial
• Histological confirmation of RCC with a clear-cell component
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC
• Intermediate or poor risk disease by International Metastatic RCC Database Consortium (IMDC) classification
• No prior systemic therapy for RCC with the following exception:
  • One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets PD-1 or PD-L1 and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Any ethnicity or race
• Calculated creatinine clearance \>= 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if liver metastases are present)
• Total bilirubin \< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin up to 3.0 mg/dL)
• White blood cells (WBC) \> 2,000/mm\^3
• Neutrophils \> 1,500/mm\^3
• Platelets \> 100,000/mm\^3