A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY OF
PARSACLISIB PLUS RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS WHO
POSTER 43
HAVE SUBOPTIMAL RESPONSE TO RUXOLITINIB
Abdulraheem Yacoub1, Michael Stouffs2, 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) is indicated for the treatment of adults with
intermediate (INT) or high-risk myelofibrosis (MF), including primary MF, post-polycythemia
vera MF and post-essential thrombocythemia MF, but a subset of patients may exhibit a
suboptimal response due to possible persistent PI3K/AKT activation. Targeting PI3K/AKT
signaling may therefore have clinically relevant effects on MF disease burden. This phase 3,
randomized, double-blind, placebo-controlled study will determine the effect of add-on
parsaclisib, a highly selective PI3Kδ inhibitor, on signs and symptoms of MF in patients with
suboptimal or declining response to stable ruxolitinib treatment (INCB 50465-304;
NCT04551053; Figure).
Methods: Eligible patients are aged ≥18 years with a diagnosis of at least INT–1-risk category
according to the Dynamic International Prognostic Scoring System (DIPSS; Passamonti. Blood.
2010;115:1703-1708) primary or secondary (post-polycythemia vera or post-essential
thrombocythemia) MF, have received ruxolitinib for ≥3 months with a stable dose (5–25 mg
twice daily) for ≥8 weeks prior to receiving the first dose of study drug (Day 1), have evidence
of suboptimal response to ruxolitinib (palpable spleen ≥5 cm below left subcostal margin, and
total symptom score ≥10), and ECOG PS ≤2. Patients are excluded if they received prior
therapy with any PI3K inhibitor, experimental or standard drug therapy for MF (except
ruxolitinib) within 3 months of starting study drug, or have platelet count <50×109/L, recent
history of inadequate bone marrow reserve, or inadequate liver or renal function at screening.
Approximately 212 patients on a stable dose of ruxolitinib will be randomized (1:1) to receive
add-on parsaclisib 5 mg daily or matching placebo beginning on Day 1, with stratification by
platelet count (≥100×109/L or 50 to <100×109/L) and DIPSS risk category (high, INT-2, or INT-
1) at randomization. Treatment will continue as long as tolerated and discontinuation criteria
are not met. When a patient has completed 24 weeks of treatment, he/she will be unblinded
and if found to be randomized to ruxolitinib plus placebo with adequate hematology
parameters, the patient will be able to crossover to receive ruxolitinib plus add-on parsaclisib.
The primary objective is to evaluate and compare the efficacy of add-on parsaclisib versus
placebo on spleen volume at Week 24. Secondary objectives are to evaluate and compare the
effect of add-on parsaclisib versus placebo on: patient-reported MF symptoms, overall
survival, time to onset and duration of spleen volume response, and safety and tolerability.
Sites are opening throughout the US, EU, China, and Japan.