A Phase II Study Bolstering Outcomes by Optimizing Immunotherapy Strategies With Evolocumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma (BOOST-RCC)

1. Histologically confirmed renal cell carcinoma (RCC), with clear-cell component, with or without sarcomatoid features

2. Prior treatment with VEGF and/or immunotherapy agent(s), including VEGF-IO combinations or IO-IO combinations, are required in the metastatic setting. If participants have not received prior VEGF and IO agents (in combination or in sequence), then documentation of participant refusal of standard of care treatment.

3. Age ≥18 years

4. 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

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 OR Karnofsky Performance Status (KPS) ≥ 70%

6. Participants must have adequate organ and marrow function as defined below:

i. absolute neutrophil count ≥ 1,500/mcL ii. platelets ≥ 100,000/mcL iii. hemoglobin (Hgb) ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

iv. 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 v. AST(SGOT)/ALT(SGPT)\* ≤ 2.5 × institutional ULN OR ≤ 5 ULN for patients with documented liver metastases vi. serum creatinine ≤ 1.5 × institutional ULN OR eGFR ≥ 40 mL/min for subject with creatinine levels \> 1.5 × institutional ULN

\*Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)-AST(SCOT)/ Alanine aminotransferase (serum glutamic-pyruvic transaminase)- ALT(SGPT)

7. Effective contraception for women of child-bearing potential (WOCBP) participants as defined by World Health Organization (WHO) guidelines for 1 "highly effective" method or 2 "effective" methods.

i. WOCBP require a negative pregnancy test to initiate treatment ii. Willingness to continue contraception for at least 5 months after the last nivolumab dose.

8. Effective contraception for men of child-bearing potential (MOCBP) participants 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.

9. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

12. Participants 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.

What this study is about