Background: Pasireotide, a novel somatostatin analog, has been previously investigated but the maximum tolerated dose (MTD) has not been determined in pts with advanced NET. We report results of a planned interim analysis of a phase I dose-escalation (DE) study to determine the MTD, characterize safety, tolerability, PK, and efficacy trends in pts with advanced NET. Methods: Pts were enrolled in 2 phases: DE phase (to determine the MTD) at a starting dose of 80mg PAS i.m. followed by a dose expansion (DX) phase (evaluate safety and preliminary efficacy). Associations between PK parameters and clinical outcomes (probability of bradycardia, % tumor shrinkage, and glucagon levels) were evaluated using regression analysis. Bradycardia is defined as heart rate < 40 bpm. Results: As of July-2015, 29 pts (15, DE; 14, DX) were treated with 80 mg (13pts) and 120 mg (16pts) doses. No protocol defined dose-limiting toxicities were observed in the study; however in a post hoc analysis a higher incidence of bradycardia was seen with 120 mg (31.3%) vs 80 mg (0%). At data cut-off, 92.3% in 80 mg and 75% pts in 120 mg had discontinued treatment; primarily due to disease progression (44.8%) or adverse events (AEs; 27.6%). In the PK analysis, probability of bradycardia showed a moderate increase with increasing PAS concentration that was not statistically significant [Odds ratio for every 1.5x increase (95% CI): daytime, 1.672 (0.381-7.338); nighttime, 2.024 (0.494-8.292)]. No significant association was observed between PAS concentrations and glucagon levels. Two partial radiographic responses (PRs) were observed, both in the 120mg dose. PAS concentrations correlated with % tumor shrinkage although the association was not statistically significant (P= 0.08). The most common AEs in the 80 mg vs 120 mg were hyperglycemia (76.9% vs 81.3%), fatigue (53.8% vs 50%) and nausea (53.8% vs 31.3%). Conclusions: MTD was defined at 120 mg for PAS in pts with advanced NET. Although objective radiographic responses are rarely observed with SSA, 2 PRs were observed among 16 pts in the 120mg cohort. Bradycardia appears to be a dose-limiting effect, however the mechanism and clinical significance are uncertain. Clinical trial information: NCT01364415