ESK981 and Nivolumab for the Treatment of Metastatic Castration Resistant Prostate Cancer

PRIMARY OBJECTIVES: I. To determine the prostate specific antigen (PSA) \>= 50% response rate (PSA50) from baseline using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981) plus nivolumab in men with metastatic castration resistant prostate cancer (mCRPC) who have progressed on enzalutamide (an oral androgen-receptor inhibitor) and/or abiraterone acetate (an androgen synthesis inhibitor) and chemotherapy (docetaxel and/or cabazitaxel). II. To assess the safety and tolerability of ESK981 plus nivolumab. SECONDARY OBJECTIVES: I. To determine the time to PSA response (TTPR) in patients with mCRPC. II. To determine the duration of PSA response (PRD) in patients with mCRPC. III. To determine PSA progression rates as defined by the PCWG3 criteria. IV. To determine PSA progression free survival (PPFS) as defined by the PCWG3 criteria. CORRELATIVE/EXPLORATORY/TERTIARY OBJECTIVE: I. To assess exploratory biomarkers from blood and tumor biopsies. OUTLINE: Patients receive ESK981 orally (PO) once daily (QD) for 5 consecutive days per week, followed by a 2-day break. Patients also receive nivolumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 5 years.