BACKGROUND: Pacritinib (SB1518) is a highly selective kinase inhibitor with 
specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study 
evaluated the maximum tolerated dose (MTD), safety, and clinical activity of 
pacritinib in patients with myelofibrosis (MF) and other advanced myeloid 
malignancies.
METHODS: In the phase 1 dose-escalation part of the study, 43 adults with 
advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD). 
In the phase 2 part of the study, 31 adults with refractory or intermediate- or 
high-risk newly diagnosed MF and any degree of cytopenia received pacritinib 
400 mg QD. The primary endpoint is a ≥35% reduction in spleen volume at week 24 
as determined by magnetic resonance imaging.
RESULTS: Five patients (11.6%) experienced a dose-limiting toxicity during cycle 
1 of phase 1. The clinical benefit rate was 86.0% (13 patients achieving 
clinical improvement and 24 patients having stable disease). The MTD was 
established at 500 mg QD, and the recommended phase 2 dose was 400 mg QD. In 
phase 2, the primary endpoint was achieved by 23.5% of evaluable patients 
(4/17), with 47.4% (9/19) achieving a ≥50% spleen length reduction at week 24 as 
measured by physical examination. At week 24, 38.9% of evaluable patients (7/18) 
achieved a ≥50% decrease in MF Quality of Life and Symptom Assessment total 
score. Gastrointestinal toxicities were the most common adverse events and were 
predominantly grade 1/2 in severity. Grade 3/4 anemia was reported in 5/31 
patients and grade 3/4 thrombocytopenia was reported in 3/31 patients. The most 
frequent AEs considered to be treatment related were diarrhea (28/31), nausea 
(15/31), vomiting (9/31), and fatigue (4/31). Grade 3 treatment-related AEs were 
reported in seven patients (22.6%), four of whom had diarrhea. No grade 4/5 
treatment-related AEs were reported. No leukopenia, neutropenia, or lymphopenia 
were reported.
CONCLUSIONS: Pacritinib was well tolerated and demonstrated clinical activity in 
MF. The study suggests that pacritinib has unique characteristics, namely a lack 
of substantial myelosuppression and manageable side effects, making it an 
attractive target for further evaluation in MF.
TRIAL REGISTRATION: Retrospectively registered at www.clinicaltrials.gov (# 
NCT00719836 ) on July 20, 2008.