Phase 2 Clinical Evaluation of Combination Immunotherapy for Renal Cell Carcinoma
This phase II trial tests adding VSV-IFNβ-NIS to standard of care ipilimumab and nivolumab for the treatment of clear cell renal cell carcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). A virus modified in the laboratory, such as VSV-IFNβ-NIS, may be able to kill tumor cells without damaging normal cells. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with ipilimumab and nivolumab may be effective for the treatment of advanced or metastatic clear cell renal cell carcinoma.
• Age ≥ 18 years
• Disease Characteristics:
⁃ Histological confirmation of advanced (not amenable to curative surgery or radiation therapy) or metastatic \[American Joint Committee on Cancer (AJCC) version 8 Stage IV\] renal cell carcinoma (RCC) with a clear cell component, including all International Metastatic RCC Database Consortium (IMDC) risk categories (favorable, intermediate, and poor risk) allowed
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
⁃ NOTE: Liver lesions that have been previously embolized (bland embolization, chemo- or radio-embolization) or have undergone percutaneous thermoablation are not eligible as target lesions. Tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 15 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
• Prothrombin time (PT)/international normalization ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance ≥ 50 ml/min using the chronic kidney disease epidemiology (CKD-EPI) creatinine equation (per National Kidney Foundation) (obtained ≤ 15 days prior to registration)
⁃ NOTE: See calculator at National Kidney Foundation website here: https://www.kidney.org/professionals/kdoqi/gfr\_calculator
• Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Willingness to provide mandatory blood specimens for correlative research
• Willingness to provide mandatory tissue specimens for correlative research
• Willing to return to Mayo Clinic for follow-up (during the active monitoring phase of the study)