Background: Aurora kinases represent potential targets for anticancer therapy in solid tumors and hematological malignancies. The aurora B kinase inhibitor AZD1152 (barasertib) has shown benefit in patients (pts) with untreated AML versus low-dose AraC when given as a 7-day continuous infusion. AZD2811 nanoparticle is a novel, encapsulated slow release inhibitor of aurora kinase B which offers several advantages compared to AZD1152 (Ashton S et al., Sci Transl Med 2016). AZD2811 nanoparticle mimics the AZD1152 7-day continuous infusion as a 2-hr infusion on Day 1 and 4, and resulted in increased efficacy preclinically. We report the first-in-man dose-escalation of AZD2811 in pts with advanced solid tumors (NCT02579226). The objectives were to determine the MTD, safety profile, dosing schedule and preliminary efficacy of AZD2811. Methods: Adult pts with advanced solid tumors were given AZD2811 nanoparticle IV on Day 1 and 4 every 28 days. Pts were enrolled according to a standard 3+3 design. Pharmacokinetics (PK) were assessed in cycle 1. Results: 24 pts were treated in 6 cohorts: 15 mg (3 pts), 25 mg (3 pts), 38 mg (3 pts), 51 mg (3 pts), 100 mg (3 pts) and 200 mg (9 pts). Of those 24 pts, 20 pts discontinued due to disease progression, (1 pt) due to death, (1 pt) withdrew consent (1 pt), physician’s decision. Preliminary efficacy indicated one confirmed ongoing partial remission in cohort 6 at 16 months. In Cohorts 1-5, common treatment-related AEs (any grade) were diarrhea, nausea, and fatigue; in Cohort 6 (200 mg per infusion) common treatment-related AEs (any grade) were fatigue, decreased appetite, and neutropenia (5 pts, all grade 4 including 1 DLT of > 7 days without G-CSF), an expected pharmacodynamics marker of target engagement. There were no infections, fever of unknown origin or treatment-related deaths. AZD2811 total blood PK appear dose proportional with a t_1/2 of 30-50 hours. Conclusions: AZD2811 nanoparticle is safe and well tolerated at a dose of 200 mg Day 1 and 4 every 28-days. A single day 1 infusion once every 21 days with G-CSF is also being investigated. Further safety and updated efficacy data will be reported at the annual meeting. Clinical trial information: NCT02579226