A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF
RUXOLITINIB PLUS PARSACLISIB IN PATIENTS WITH JAK- AND PI3K-INHIBITOR
POSTER 42
TREATMENT–NAÏVE MYELOFIBROSIS
Abdulraheem Yacoub1, Sue Erickson-Viitanen2, Feng Zhou2 and Albert Assad2
(1)University of Kansas Medical Center, Kansas City, KS, USA
(2)Incyte Corporation, Wilmington, DE, USA
Background: Ruxolitinib (JAK1/JAK2 inhibitor) significantly improves outcomes in patients
with myelofibrosis (MF); however, a subset of patients may experience a suboptimal response.
Recent phase 2 data showed that addition of PI3Kδ inhibitor parsaclisib to ruxolitinib
monotherapy resulted in additional alleviation of MF symptoms and splenomegaly in patients
with MF (Yacoub. EHA2020. S216). This phase 3, randomized, double-blind study (INCB 50465-
313; NCT04551066), evaluates the combination of ruxolitinib and parsaclisib in patients with
MF who are naïve to Janus kinase (JAK) and PI3K inhibitor therapies (Figure).
Methods: Eligible patients are aged ≥18 years with a diagnosis of primary MF, post-polycythemia
vera MF, or post-essential thrombocythemia MF, have a Dynamic International
Prognostic Scoring System (DIPSS; Passamonti. Blood. 2010;115:1703-1708) risk category of
at least Intermediate (INT)-1, palpable spleen ≥5 cm below left subcostal margin; total
symptom score ≥10 at screening, ECOG PS 0–2, and life expectancy ≥24 weeks. Patients will
be excluded if they previously received therapy with any JAK inhibitor, any PI3K inhibitor, any
experimental or standard drug therapy for MF ≤3 months of first study dose and/or lack of
recovery from all toxicities related to previous therapies to grade ≤1, have recent history of
inadequate bone marrow reserve (eg, platelet count <50×109/L) or have inadequate liver or
renal function at screening.
Approximately 440 patients will be randomized (1:1) to ruxolitinib plus parsaclisib 5 mg QD or
ruxolitinib plus matching placebo, with stratification at randomization by DIPSS risk category
(high vs INT-2 vs INT-1) and platelet count (≥100×109/L vs 50 to <100×109/L inclusive).
Treatment will begin on Day 1, with starting ruxolitinib dose level determined by baseline
platelet count, and will continue as long as treatment is tolerated and discontinuation criteria
are not met. When the last enrolled patient has completed 24 weeks of treatment, the study
will be unblinded and patients randomized to ruxolitinib plus placebo who have adequate
hematology parameters will be able to crossover to receive parsaclisib together with
continued ruxolitinib.
The primary objective is the evaluation and comparison of spleen volume at Week 24 for
patients who received ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Secondary
objectives include evaluation and comparison of patient-reported MF symptoms, overall
survival, time to onset and duration of response in spleen volume, and safety and tolerability
for ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Sites are opening across the US,
Canada, EU, and Asia.