Background: UM metastases occur in 50% of cases and high-risk pts are identified by a gene expression profile. High-dose IPI is approved for adjuvant (adj) treatment (tx) of cutaneous melanoma and NIVO + IPI for metastatic (met) melanoma, yet the safety and efficacy of high-dose IPI or NIVO + IPI has not been established in UM in the adj or met settings. Methods: We performed a phase I/II trial of IPI for the tx of high-risk & met UM (CA184-187). The study consisted of two arms: an adj arm (AA) & met arm (MA) with two dose levels, 3 mg/kg & 10 mg/kg. Dose-finding proceeded on each arm in a 3 + 3 fashion. Pts received IPI once every 3 weeks for four doses followed by maintenance IPI every 12 weeks (for up to one year in AA). The AA treated pts with a Class 2 gene expression profile. This score imparts a 3-year distant metastasis-free survival (DMFS) of 50%. The primary endpoint for the AA was maximum tolerated dose (MTD) and improvement in 3-year DMFS to 70%. The primary endpoint for the MA was MTD & overall survival. The study was later amended to include a cohort of UM pts treated with combination NIVO + IPI in the standard FDA approved schedule. Results: Ten pts were enrolled on AA, 18 on MA, and 20 on NIVO + IPI. Adverse events (AEs) of any Grade (Gr) related to tx occurred in 80% of pts on AA. Gr 3/4 related toxicities observed in more than one pt were: transaminitis (30%) & pruritus (20%). Of these, 10% of the elevated AST and ALT and 10% of the pruritus occurred during the dose-finding portion of the trial at 3 mg/kg. One pt developed biopsy-proven colitis, and one developed diarrhea. Both were treated with high-dose steroids. One pt developed vasculitis manifesting as temporal arteritis with resultant blindness. AEs of any Gr occurred in 44% of pts on MA. Gr 3/4 toxicities observed in more than one pt were: Fatigue (11%) and Hyperbilirubinemia (11%). Only 1 pt (5.6%) developed Gr 3/4 diarrhea, and this was at the 3 mg/kg dose. In the NIVO + IPI cohort, Gr 3 transaminitis & elevated TSH occurred in 10%. Conclusions: High-dose IPI in UM did not demonstrate new or unexpected toxicities. Similarly, the combination of NIVO + IPI was well-tolerated with no new toxicities. Efficacy data will be presented at the meeting. Clinical trial information: NCT01585194