ADDITION OF PARSACLISIB (INCB050465), A PI3KΔ INHIBITOR, IN PATIENTS
WITH SUBOPTIMAL RESPONSE TO RUXOLITINIB: A PHASE 2 STUDY IN
PATIENTS WITH MYELOFIBROSIS
Abdulraheem Yacoub1, Eunice S. Wang2, Raajit Rampal3, Uma Borate4, Marina Kremyanskaya5, Haris
Ali6, Gabriela S. Hobbs7, Casey O’Connell8, Albert Assad9, Sue Erickson-Viitanen9, Feng Zhou9, Timothy
C. Burn9 and Naval Daver10
(1)University of Kansas Medical Center, Kansas City, KS, USA
(2)Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
(3)Memorial Sloan Kettering Cancer Center, New York, NY, USA
(4)Oregon Health & Science University, Portland, OR, USA
(5)Mount Sinai Hospital, New York, NY, USA
(6)City of Hope Comprehensive Cancer Center, Duarte, CA, USA
(7)Massachusets General Hospital, Boston, MA, USA
(8)University of Southern California, Los Angeles, CA, USA
(9)Incyte Corporation, Wilmington, DE, USA
(10)The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Background: Ruxolitinib improves outcomes in patients with myelofibrosis (MF); however,
suboptimal response may occur due to persistent PI3K/AKT pathway activation despite
continued JAK inhibition. This phase 2 study (NCT02718300) evaluated optimal dosing and
efficacy of add-on parsaclisib, a potent, highly selective next-generation PI3Kδ inhibitor, in
patients with MF and suboptimal ruxolitinib response.
Methods: Patients had primary/secondary MF, ECOG ≤2, and suboptimal response (palpable
spleen >10 cm below left subcostal margin LSM; or palpable spleen 5–10 cm below LSM and
active symptoms) after ≥6 months of ruxolitinib (5–25 mg BID; stable dose, ≥8 weeks). Patients
remained on their stable ruxolitinib dose and were randomized to add-on parsaclisib QD/QW
(10 or 20 mg QD for 8 weeks/same dose QW thereafter) or parsaclisib QD (5 or 20 mg QD for
8 weeks/5 mg QD thereafter; Figure 1). Endpoints: baseline-to-week-12 spleen volume (SV)
change by MRI/CT (primary endpoint); spleen length and symptom changes (Myelofibrosis-
Symptoms Assessment Form Total Symptom Score MFSAF-TSS).
Results: At data cutoff (20 JAN 2020), 33 patients received parsaclisib QD/QW; 20 received
QD (median treatment duration, 197 days; median average daily doses: parsaclisib, 4.9
mg/day; ruxolitinib, 30.0 mg/day). Baseline median (range) SV (cm3) was 2333 (327–5324) in
QD/QW (n=30) and 1890 (434–3741) in QD (n=17); median MFSAF-TSS was 10.8 (n=28) and
18.7 (n=17). In QD/QW and QD, median percent SV change was −2.3 (n=30) and −15.4 (n=17)
at week-12; −2.5 (n=24); −25.4 (n=9) at week-24 (Figure 2: A week-12 and week-24 SV
reduction; B palpable spleen length change over time). Median percent change in MFSAF-TSS
at week-12 was −14.0 (n=21) in QD/QW; −39.6 (n=12) in QD.
Nonhematologic AEs were primarily grade 1/2. Grade 3/4 treatment-related, nonhematologic
AEs included disseminated tuberculosis, enteritis, fatigue, hypertension, increased alanine
aminotransferase, and increased aspartate aminotransferase in QD/QW and stomatitis in QD.
In QD/QW and QD, 6/33 and 6/20 patients had new-onset grade 3 thrombocytopenia; 7/33
and 0/20 patients had grade 4 thrombocytopenia; hemoglobin levels remained steady during