Background: Recurrence of high-grade glioma (HGG) (WHO grade III-IV) is a nearly universal phenomenon and necessitates the development of new therapeutic modalities. Two possible immunotherapeutic modalities are checkpoint blockade with agents such as nivolumab, a blocking antibody against the inhibitory checkpoint programmed cell death-1 (PD-1), and dendritic cell (DC) vaccination. We have shown in phase 1 and 2 trials that DC vaccination against the glioblastoma (GBM)-associated antigen human cytomegalovirus pp65-lysosomal-associated membrane protein (CMVpp65) is safe and possesses potential benefit. We hypothesized that nivolumab-induced immune checkpoint blockade could enhance efficacy of DC vaccination. Therefore, we undertook a phase 1 study to evaluate safety of nivolumab in combination with CMVpp65 mRNA pulsed DC vaccination in subjects with first or second recurrence of resectable HGG. Methods: We performed a phase 1, single-center, randomized study of nivolumab alone versus nivolumab + DC vaccination prior to planned surgical resection for both groups. We administered nivolumab 3 mg/kg IV q2weeks for 8 weeks followed by surgery and planned continuation of nivolumab. For the group receiving nivolumab + DC vaccination, we administered 3 vaccines before surgical resection with both groups receiving 5 planned post-resection DC vaccines. Primary endpoint was safety assessment using NCI-CTCAE 4.03. Results: We enrolled 6 subjects (4: GBM, 1: anaplastic astrocytoma, 1: anaplastic oligodendroglioma) with 3 receiving nivolumab alone and 3 receiving nivolumab + DC vaccination. Age range was 45-63 years subjects. We documented similar adverse events in both groups with most common grade 1-2 toxicities being fatigue (2 subjects, nivolumab alone) and thrombocytopenia (2 subjects, nivolumab + DC vaccine). Grade 4 toxicities included wound infection (2 subjects, nivolumab + DC vaccine) and meningitis (1 subject, nivolumab + DC vaccine). While we designed the study to enroll 66 subjects, we terminated the study early in light of CheckMate 143 phase III data showing nivolumab did not improve overall survival in recurrent GBM. Conclusions: Safety of nivolumab + DC vaccination in recurrent HGG is similar to nivolumab alone. Continued evaluation of new therapeutics including immunotherapy is underway for this patient population. Clinical trial information: NCT02529072