Evolocumab and Nivolumab for the Treatment of Patients with Refractory Metastatic Renal Cell Carcinoma

Inclusion Criteria

• Histologically confirmed renal cell carcinoma (RCC), with clear-cell component, with or without sarcomatoid features
• Prior treatment with VEGF and/or immunotherapy agent(s), including VEGF-IO combinations or IO-IO combinations, are required in the metastatic setting. If patients have not received prior VEGF and IO agents (in combination or in sequence), then documentation of patient refusal of standard of care treatment
• Age ≥ 18 years
• Participants or their legally acceptable representative must have signed and dated an Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 OR Karnofsky performance status (KPS) ≥ 70%
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin (Hgb) ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Total bilirubin ≤ institutional upper limit of normal (ULN) OR bilirubin < 3.0 ml/dL and direct bilirubin ≤ ULN for subjects with Gilbert’s syndrome with total bilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) ≤ 2.5 × institutional ULN OR ≤ 5 ULN for patients with documented liver metastases * Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)-AST(SCOT)/ Alanine aminotransferase (serum glutamic-pyruvic transaminase)- ALT(SGPT)
• Serum creatinine ≤ 1.5 × institutional ULN OR estimated glomerular filtration rate (eGFR) ≥ 40 mL/min for subject with creatinine levels > 1.5 × institutional ULN
• Effective contraception for women of child-bearing potential (WOCBP) patients as defined by World Health Organization (WHO) guidelines for 1 “highly effective” method or 2 “effective” methods. * WOCBP require a negative pregnancy test to initiate treatment ** Willingness to continue contraception for at least 5 months after the last nivolumab dose
• Effective contraception for men of child-bearing potential (MOCBP) patients as defined by WHO guidelines for 1 “highly effective” method or 2 “effective” methods. Sperm or egg donation/banking is not allowed during the participation of the study
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• 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

Exclusion Criteria

• Chemotherapy, immunotherapy, or other experimental cancer therapy within 2 weeks prior to starting study treatment
• Must have recovered from all anticancer treatment-related toxicities to grade 1 or less, except for alopecia and endocrinopathies that are stable on treatment with replacement therapy (immune therapy-related endocrinopathies treated with prednisone 10 mg per day [or equivalent] are acceptable)
• Patients receiving any concomitant systemic therapy for RCC are excluded. Patients must not be scheduled to receive another experimental drug while on this study
• Symptomatic brain or leptomeningeal metastases, including patients who continue to require glucocorticoids and/or antiseizure therapy. Treated, asymptomatic brain are leptomeningeal metastases are permitted, provided patient has completed radiation at least 2 weeks prior to day 1 and on a physiologic dose of steroids (prednisone equivalent 10mg daily) for at least 1 week prior to day 1 of study treatments. Stable, untreated brain metastases (based on CNS imaging > 4 weeks apart) permitted if patient does not require steroids or antiseizure therapy
• Has known hypersensitivity to any of the study drugs or excipients, including history of severe allergic, anaphylactic, or other hypersensitivity reactions to fusion proteins, or known hypersensitivity or allergy to Chinese hamster ovary cell products
• Active infection requiring systemic therapy within 14 days prior to treatment assignment
• Symptomatic congestive heart failure of New York heart Association Class III or IV * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease * Severely impaired lung function as defined as oxygen (02) saturation that is 88% or less at rest on room air * Uncontrolled hypertension (systolic blood pressure [SBP] ≥ 160 mm Hg or diastolic blood pressure [DBP] ≥ 90 mm Hg) despite treatment with antihypertensives
• Has evidence of any other medical conditions, psychiatric condition, physical examination or laboratory findings that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications in the opinion of the investigator
• Pregnant women are excluded from this study. Women who are breastfeeding should discontinue prior to initiating treatment