SBRT (Stereotactic Body Radiation Therapy) in Combination With Nivolumab/Ipilimumab in Renal Cell Carcinoma (RCC) / Kidney Cancer Patients

Inclusion Criteria:

* Histological confirmation of RCC with a clear-cell component
* Metastatic (AJCC Stage IV) RCC
* Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred = or \> 6 months after the last dose of the adjuvant or neoadjuvant therapy
* Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or clinical trial) including previously untreated patients
* Karnofsky Performance Status (KPS) of at least 70%
* Life expectancy of at least 3 months
* At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1
* Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for correlative studies (Note: Fine Needle Aspiration (FNA) and bone metastases samples are not acceptable for submission)
* Patients with favorable, intermediate and poor risk categories will be eligible for the study. Patients must be categorized according to favorable versus intermediate/poor risk status at registration. International Metastatic RCC Database Consortium (IMDC) must be used to determine prognostic factors

Exclusion Criteria:

* Subjects with previously treated brain or CNS (Central nervous system) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration. Liver metastases will not be included as part of the radiated lesions to be treated.

Medical History and Concurrent Diseases:

* Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2, anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose interleukin (HD IL)-2 is allowed.
* 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. Patients with psoriasis not requiring active, systemic treatment are allowed.
* 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 up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* Uncontrolled adrenal insufficiency
* Requirement for anti-coagulation with Coumadin, low molecular weight heparin and anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at least 4 weeks and no recent history of prior bleeding complications.
* Prior malignancy active within the previous 3 years 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 cervix, breast or low risk Gleason 6 prostate cancer
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
* Known medical condition (eg, 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
* Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug
* Anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug
* Presence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug

Physical and Laboratory Test Findings:

* Any of the following laboratory test findings:

  * White blood cell (WBC) \< 2,000/mm3
  * Neutrophils \< 1,500/mm3
  * Platelets \< 100,000/mm3
  * 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 \< 3.0 mg/dL)
  * Serum creatinine \> 1.5 x upper limit of normal (ULN) or creatinine clearance \< 40 mL/min (measured or calculated by Cockroft-Gault formula)

Allergies and Adverse Drug Reaction:

* History of severe hypersensitivity reaction to any monoclonal antibody or study drug components

Other Exclusion Criteria:

* Prisoners or subject who are involuntarily incarcerated
* Not suitable for SBRT treatment
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness