Phase 2 trial results suggest that parsaclisib can reduce spleen volume and improve symptom burden in patients with myelofibrosis (MF) who have a suboptimal response to a stable dose of ruxolitinib.
These results were presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO) by Abdulraheem Yacoub, MD, of the University of Kansas Cancer Center in Kansas City.
Dr Yacoub noted that suboptimal responses to ruxolitinib may be due to activation of the PI3K signaling pathway, and parsaclisib is a PI3Kδ inhibitor.
In a phase 2 study (ClinicalTrials.gov Identifier: NCT02718300), Dr Yacoub and colleagues evaluated the optimal dosing, efficacy, and safety of parsaclisib in patients with MF who were receiving ruxolitinib at a stable dose but having a suboptimal response.
The study enrolled 67 adults with primary or secondary MF. They had received ruxolitinib, at 5 mg to 25 mg twice daily, for at least 6 months and were receiving a stable dose for at least 8 weeks prior to enrollment.
Roughly half of patients were randomly assigned to receive parsaclisib at 10 mg or 20 mg once daily for 8 weeks and the same dose once weekly thereafter (n=32).
The other half were randomly assigned to receive parsaclisib at 5 mg or 20 mg once daily for 8 weeks, followed by 5 mg once daily thereafter (n=35). Patients in both arms remained on their stable ruxolitinib dose during the study.
About half of patients in each arm had primary MF. The median time from initial diagnosis to baseline was 30.5 months in the daily/weekly dosing arm and 37.3 months in the all-daily dosing arm.
Dr Yacoub noted that patients had “significant” splenomegaly and symptom burden at baseline, despite using ruxolitinib for a median of 1.5 years. The median duration of ruxolitinib treatment was 18.3 months in the daily/weekly dosing arm and 16.7 months in the all-daily dosing arm.
The median spleen volume at baseline was 2414.5 cm3 in the daily/weekly dosing arm and 1885.3 cm3 in the all-daily dosing arm. The median total symptom score was 10.8 and 16.3, respectively.
The median duration of study treatment was 48.9 weeks in the daily/weekly dosing arm and 24.4 weeks in the all-daily dosing arm.
At 12 weeks, most patients had a reduction in spleen volume. The median percentage change in spleen volume was −1.9% (n=29) in the daily/weekly dosing arm and −13.0% (n=27) in the all-daily dosing arm. At week 24, the median change in volume was −3.5% (n=23) and −21.8% (n=17), respectively.
At weeks 12 and 24, a greater percentage of patients in the all-daily dosing arm achieved at least a 10%, 25%, or 35% reduction in spleen volume compared with patients in the daily/weekly dosing arm.
A larger proportion of patients in the all-daily dosing arm had a 50% or greater improvement in their symptoms. At week 12, the median percentage change in total symptom score was −14.0% (n=21) in the daily/weekly dosing arm and −37.4% (n=17) in the all-daily dosing arm.
Nonhematologic treatment-emergent adverse events (TEAEs) were primarily grade 1-2 in nature. TEAEs of special interest in the daily/weekly dosing arm were grade 2 or higher diarrhea (n=4) and grade 3 or higher elevated ALT/AST (n=2 for both). The only TEAE of special interest in the all-daily dosing arm was herpes simplex virus (n=2).
New-onset grade 3 thrombocytopenia was more common in the all-daily dosing arm (26%) than in the daily/weekly dosing arm (19%). However, new-onset grade 4 thrombocytopenia was more common in the daily/weekly arm (19%) than in the all-daily arm (3%).
Hemoglobin levels remained steady over time in both treatment arms during the study.
TEAEs led to parsaclisib discontinuation in 7 patients in the daily/weekly dosing arm and 3 patients in the all-daily dosing arm. Two patients in the daily/weekly arm and 1 in the all-daily arm discontinued ruxolitinib.
Dr Yacoub said these results informed the development of phase 3 studies of parsaclisib as an add-on to ruxolitinib (ClinicalTrials.gov Identifier: NCT04551053) and parsaclisib plus ruxolitinib in the frontline setting (ClinicalTrials.gov Identifier: NCT04551066). Both studies are currently enrolling patients.
Disclosures: This research was supported by Incyte Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Yacoub A, Borate U, Rampal R, et al. Add-on parsaclisib (a PI3Kδ Inhibitor) in patients with myelofibrosis and suboptimal response to ruxolitinib: Interim analysis from a phase 2 study. Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021.
This article originally appeared on Cancer Therapy Advisor