Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma

Inclusion Criteria:

• Be willing and able to provide informed consent for the trial

• Histological confirmation of renal cell carcinoma (RCC) with a clear-cell orsarcomatoid component

• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer [AJCC] 8 stage IV) RCC

• Intermediate or poor risk disease by International Metastatic Renal Cell CarcinomaDatabase Consortium Criteria (IMDC) classification

• No prior systemic therapy for RCC with the following exception:

• One prior adjuvant or neoadjuvant therapy for completely resectable RCC if suchtherapy did not include an agent that targets PD-1 or PD-L1 and if recurrenceoccurred at least 6 months after the last dose of adjuvant or neoadjuvanttherapy

• Eastern Cooperative Oncology Group (ECOG) performance status < 2

• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Males and females, ages >= 18

• Any ethnicity or race

• Adequate renal function defined as calculated creatinine clearance >= 30 millilitersper minute (mL/min) per the Cockcroft and Gault formula or Serum creatinine < 1.5 xupper limit of normal (ULN)

• Adequate liver function defined by aspartate aminotransferase (AST) or alanineaminotransferase (ALT) < 3 x ULN (< 5 x ULN if liver metastases are present), andtotal bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can havetotal 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

Exclusion Criteria:

• Presence of untreated brain metastases. Patients with treated brain metastases mustbe stable for 4 weeks after completion of treatment and have documented stability onpre-study imaging. Patients must have no clinical symptoms from brain metastases andhave no requirement for systemic corticosteroids amounting to > 10 mg/day ofprednisone 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

• Favorable risk disease by IMDC classification

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, oranti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cellco-stimulation or checkpoint pathways

• Any active or recent history of a known or suspected autoimmune disease or recenthistory of a syndrome that required systemic corticosteroids (> 10 mg dailyprednisone equivalent) or immunosuppressive medications except for syndromes whichwould not be expected to recur in the absence of an external trigger. Subjects withvitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmunethyroiditis only requiring hormone replacement are permitted to enroll

• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitisrequiring treatment with systemic steroids

• Baseline pulse oximetry less than 92% "on room air"

• Current use, or intent to use probiotics, prebiotics, yogurt, bacterial fortifiedfoods and other natural supplements =< 2 week prior to treatment initiation andduring the period of treatment

• Any condition requiring systemic treatment with corticosteroids (> 10 mg dailyprednisone equivalents) or other immunosuppressive medications within 14 days priorto first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of activeautoimmune disease

• Uncontrolled adrenal insufficiency

• Known medical condition (e.g., a condition associated with diarrhea or acutediverticulitis) that, in the investigator's opinion, would increase the riskassociated with study participation or study drug administration or interfere withthe interpretation of safety results

• Not recovered to =< Grade 1 toxicities related to any prior therapy beforeadministration of study drug

• Women who are pregnant or breastfeeding

• History of myocarditis or congestive heart failure (as defined by New York HeartAssociation Functional Classification III or IV), as well as unstable angina,serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardialinfarction 6 months prior to study entry

• WBC < 2,000/mm^3

• Neutrophils < 1,500/mm^3

• Platelets < 100,000/mm^3

• AST or 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 havetotal bilirubin 3.0 mg/dL)

• Calculated creatinine clearance <30 millimeters per minute (mL/min) per theCockcroft and Gault formula or serum creatinine > 1.5 x upper limit of normal (ULN)