Clinical Research Directory

Inclusion Criteria: * Patient must be \>= 18 years of age. * Patient must have a biopsy/pathologically (histologically or cytologically) proven diagnosis of clear cell renal cell carcinoma (ccRCC) prior to randomization. * Patient must have at least 1 and not more than 5 metastatic lesions measurable by RECIST v1.1, with imaging obtained within 45 days prior to randomization. * Patients with untreated brain metastasis measuring \<2cm in diameter (intracranial RANO-BM measurable disease required) and with minimal neurological symptoms. Patients with treated brain metastasis are eligible for the trial as long as they have had three or fewer brain metastasis without signs of progression of disease on post-treatment MRI of the brain as per RANO for Brain Metastases (RANO-BM) guidelines. * Patient must have documentation from a radiation oncologist confirming that all sites (metastases and primary tumor, if present) are amenable to stereotactic body radiation therapy (SBRT). * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. * All patients of childbearing potential must have a serum test within 14 days prior to randomization to rule out pregnancy. * Patient must have the ability to understand and the willingness to sign a written informed consent document. * Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. * Patients must have adequate organ and bone marrow function per protocol. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study. * For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study. * For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study. * Patients with prior radiation to sites but without evidence of progression will be allowed, however these RT-treated sites will not be treated on study. Patients who have had a prior nephrectomy can be included in the study, patients with prior metastasectomy are also eligible for the study. Exclusion Criteria: * Patients with untreated brain metastasis \>2cm, significant neurological deficits and unamenable to surgical resection. * Patient with variant histology renal cell carcinoma. * Patient with metastasis invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum). * Patients with more than 2 liver metastatic lesions, or liver lesions resulting in obstructive jaundice. * Patient who have received any prior combination systemic therapy for metastatic RCC (including immune checkpoint inhibitors, tyrosine kinase inhibitors or combinations) * Patients who have received any check point inhibitor or immune therapies (i.e. Vaccine or other immune-oncology agent) within the last 12 months. Patients who have previously been treated for non-metastatic RCC with adjuvant pembrolizumab can be included if over 12 months since last dose and they have not had radiographic progression within 12 months from the last dose of pembrolizumab * Patients with active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. * Patients with no more than 1 prior systemic therapy for metastatic disease. * Patients with active tuberculosis per protocol. * Patients with uncontrolled hypertension (systolic blood pressure \[BP\] \> 190mmHg or diastolic BP \> 110mmHg). * Patients requiring major surgery within 30 days prior to randomization. * Patients with any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization. * Patients with any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-STEMI \[NSTEMI\], cerebrovascular accident \[CVA\], etc.) events within 180 days prior to randomization. * Patients with moderate or severe hepatic impairment (child-Pugh B or C). * Patients with untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed. * Patients with unstable cardiac arrhythmia within 180 days prior to randomization. * Patients with history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization. * Patients with history of or active inflammatory bowel disease. * Patients with history of connective tissue disease or other disease in which radiation therapy is contraindicated. * Patient pregnant or breastfeeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. * Patients must not expect to conceive or father children and should use accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment. * Patients with a history of myocarditis. * Patients with troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline per protocol. * Patients with history or current evidence of significant (CTCAE grade ≥2) local or systemic infection (e.g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication. * Patients with active infection requiring therapy. * Patients with ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment. * Patients with uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection per protocol. * Patients with known hypersensitivity to the active substances or to any of the excipients. * Patients who received a live vaccine within 30 days of planned start of study medication per protocol. * Women who are fertile following menarche until becoming postmenopausal or women of childbearing potential (WOCBP\*), unless permanently sterile must have a negative serum (beta-hCG) at screening per protocol. * Pregnant or breastfeeding women.