Investigator-Initiated Trial of Combined Ipilimumab, Nivolumab and Stereotactic Radiation in Patients With Metastatic Clear-Cell RCC (ccRCC) Who Have Failed Treatment With Single-Agent Nivolumab

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of metastatic ccRCC.
* Age 18 years and older
* ECOG 0-1
* Progressive disease after treatment with single-agent nivolumab
* Life expectancy at least 3 months
* Presence of measurable disease per RECIST 1.1 criteria
* Presence of a metastatic lesion greater than 1 cm in size that is amenable to radiation treatment
* Adequate organ system function
* WOCBP and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception.

Exclusion Criteria:

* Patients are excluded if they have active brain metastases or leptomeningeal metastases (exceptions outlined in the protocol).
* Active, known or suspected autoimmune disease, such as systemic lupus erythematosus, that require treatment with immune suppressing drugs.

Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

* Presence of a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of study drug administration.

Note: Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

* Unstable angina or uncontrolled congestive heart failure
* Uncontrolled hypercalcemia
* Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Presence of other malignant diseases, except non-melanoma skin care
* History of allergy to study drug components.
* History of severe hypersensitivity reaction to any monoclonal antibody.
* Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration.
* Women must not be pregnant or breastfeeding. WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration.
* Any other medical condition for which treatment with ipilimumab or nivolumab would be medically contraindicated