Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

Inclusion Criteria:

   - Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell
   carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned

   - If histological confirmation of RCC has not been done within 12 months prior to
   randomization, patient must be willing to undergo a core biopsy for this purpose if
   randomized to Arm A

      - NOTE: This histologic confirmation can be a (1) standard of care diagnostic
      biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be
      obtained with results available prior to the neoadjuvant dose

         - Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC
         of any histology, including sarcomatoid, unclassified, or "unknown
         histology" (if preoperative biopsy was uninformative) with exception below
         for non-diagnostic biopsies

         - If the biopsy performed following randomization clearly demonstrates a
         benign condition, oncocytoma or a different type of cancer that is not RCC,
         the patient is not eligible and must come off study

         - A non-diagnostic biopsy is considered a good faith effort and does not need
         to be repeated unless deemed clinically necessary by the treating
         investigator

   - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
   or 1

   - Patients with a prior RCC that was treated > 5 years before are eligible if the
   current tumor is consistent with a new primary in the opinion of the treating
   investigator

   - Patients with bilateral synchronous RCCs are eligible if they can be resected or
   definitively treated at the same time or within a 12 week window from time of initial
   nephrectomy (partial or radical) or procedure and maintain adequate residual renal
   function; the patient is not eligible if both kidneys are to be completely removed and
   subsequent hemodialysis will be required

      - Permitted forms of local therapy for second tumor:

         - Partial or radical nephrectomy

         - If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency ablation,
         cryoablation or stereotactic radiosurgery)

   - Patient must have the ability to understand and the willingness to sign a written
   informed consent document

   - White blood cells >= 2000/uL (within 8 weeks prior to randomization)

   - Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization)

   - Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization)

   - Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization)

   - Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine
   clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization)

   - Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have
   total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization)

   - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
   (within 8 weeks prior to randomization)

Exclusion Criteria:

   - Clinical or radiological evidence of distant metastases (M0) unless the presumed M1
   disease is planned to be resected/definitively treated (e.g., thermal ablation,
   stereotactic radiation) at the same time or up to 12 weeks after the date of the
   initial procedure such that the patient is considered "no evidence of disease" (M1
   NED)

      - Liver, bone, or brain metastases are not permitted

      - No more than 3 metastases are permitted, and all must be able to be removed or
      definitively treated within 12 weeks of the primary tumor resection

   - Prior systemic or local anti-cancer therapy for the current RCC, including:

      - Partial nephrectomy for the current RCC

      - Metastasectomy for the current RCC diagnosis unless performed to render patient
      NED (in addition to the planned nephrectomy) within 6 months prior to the current
      diagnosis

      - Current or past antineoplastic systemic therapies for RCC: i.e., chemotherapy,
      hormonal therapy, immunotherapy, or standard or investigational agents for
      treatment of RCC

      - 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

   - History of RCC that was treated with curative intent within the past 5 years

   - Concurrent malignancies, with the following exceptions:

      - Adequately treated basal cell or squamous cell skin cancer

      - In situ cervical cancer

         - A history of superficial Ta urothelial cancer is permitted (as long as not
         currently undergoing treatment) whereas T1 or greater disease is excluded if
         < 3 years from diagnosis; concurrent persistent disease is not permitted

         - Adequately treated stage I or II cancer from which the patient is currently
         in complete remission

         - Any other cancer and stage from which the patient has been disease-free for
         at least 3 years prior to the time of randomization and as long as they are
         not receiving any current treatment (e.g. adjuvant or maintenance systemic
         or local therapy)

         - Concurrent low risk prostate cancer on active surveillance

   - Active known or suspected autoimmune disease. The following autoimmune disorders are
   permitted: patients with vitiligo, type I diabetes mellitus, controlled/stable hypo or
   hyperthyroidism due to autoimmune or non-autoimmune conditions (hormone replacement is
   allowed), psoriasis not requiring systemic treatment, or other conditions not expected
   to recur

   - Ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg
   daily prednisone equivalent) or other immunosuppressive medications with the
   exceptions outlined below

   - Any treatment with other immunosuppressive agents within 14 days prior to the first
   dose of study drug with the following exceptions:

      - Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal
      replacement steroid doses > 10 mg daily prednisone or the equivalent are
      permitted in the absence of active autoimmune disease

      - A brief (less than 3 weeks) course of corticosteroids (any amount) for
      prophylaxis (for example: contrast dye allergy) or for treatment of
      non-autoimmune conditions (for example: nausea, delayed-type hypersensitivity
      reaction caused by a contact allergen) is permitted

   - Uncontrolled adrenal insufficiency

   - Known evidence of chronic active liver disease or evidence of acute or chronic
   hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing must be completed
   within 8 weeks prior to randomization

      - NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid
      (RNA) is undetectable, the patient is eligible for this study

   - Serious intercurrent illness, including ongoing or active infection requiring
   parenteral antibiotics

   - Known evidence of human immunodeficiency virus (HIV) infection, since the effects of
   nivolumab on anti-retroviral therapy have not been studied; HIV testing is only
   required if past or current history is suspected

   - Known medical condition (e.g. a condition associated with uncontrolled diarrhea such
   as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion,
   would increase the risk associated with study participation or interfere with the
   interpretation of safety results

   - Major surgery within 28 days prior to randomization

   - Concurrent enrollment in other clinical trials testing a therapeutic intervention

   - History of severe hypersensitivity to a monoclonal antibody

   - Pregnant or breast-feeding, as the effects of nivolumab on the developing human fetus
   or in the nursing infant are unknown; all patients of childbearing potential must have
   a blood test or urine study within 2 weeks prior to randomization to rule out
   pregnancy; a patient of childbearing potential is defined as any woman, regardless of
   sexual orientation or whether they have undergone tubal ligation, who meets the
   following criteria: 1) has achieved menarche at some point 2) has not undergone a
   hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal
   for at least 24 consecutive months (i.e., has had menses at any time in the preceding
   24 consecutive months)

   - Patients must not expect to conceive or father children by using accepted and
   effective method(s) of contraception, as described in the informed consent form (ICF),
   or by abstaining from sexual intercourse for the duration of their participation in
   the study; patients of childbearing potential must use adequate methods to avoid
   pregnancy for 5 months after the last dose of nivolumab