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1502 A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Add-on Parsaclisib in Patients with Myelofibrosis Who Have Suboptimal Response to RuxolitinibClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Clinical Research, Clinically Relevant, Diseases, Therapies, Adverse Events, Study Population
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Abdulraheem Yacoub, MD1*, Thamer Sliwa, MD2*, Hideto Tamura, MD, PhD3, Michael Stouffs, PhD4*, Feng Zhou, PhD4* and Albert Assad, MD4*

1University of Kansas Medical Center, Kansas City, KS
2Hanusch Hospital, Vienna, Austria
3Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
4Incyte Corporation, Wilmington, DE

Background: Ruxolitinib is a Janus kinase (JAK)1/JAK2 inhibitor, 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 phosphatidylinositol 3 kinase (PI3K)/AKT activation. Targeting PI3K/AKT signaling may therefore have clinically relevant effects on MF disease burden.

Aims: 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).

Methods: Eligible patients are ≥18 years of age with a diagnosis of primary or secondary (post–polycythemia vera or post-essential thrombocythemia) MF with at least INT-1–risk (according to the Dynamic International Prognostic Scoring System [DIPSS]; Passamonti F. Blood. 2010;115:1703–8). Patients must 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), and have evidence of suboptimal response to ruxolitinib (palpable spleen ≥5 cm below left subcostal margin and total symptom score ≥10 at screening on the Screening Symptom Form). They must also have an Eastern Cooperative Oncology Group performance status ≤2 and a life expectancy of ≥24 weeks. Patients are excluded if they have received prior therapy with any PI3K inhibitor, experimental or standard drug therapy for MF (except ruxolitinib) within 3 months of starting the study drug, a recent history of inadequate bone marrow reserve (platelet count <50×109/L, absolute neutrophil count <0.5×109/L, peripheral blood blast count >10%), or have 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 inclusive) and DIPSS risk category (INT-1, INT-2, or high) at randomization (Figure 1). Treatment will continue as long as the patient does not meet the discontinuation criteria. 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 cross over to receive ruxolitinib plus add-on parsaclisib. The primary objective is to evaluate and compare the efficacy of add-on parsaclisib vs placebo on spleen volume at week 24. Secondary objectives are to evaluate and compare the effect of add-on parsaclisib vs placebo on patient-reported MF symptoms, overall survival, time to onset and duration of spleen volume response, and safety and tolerability. Sites are open throughout North America, Europe, and Asia.

Disclosures: Yacoub: Incyte: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Acceleron Pharma: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees. Stouffs: Incyte: Current Employment, Current equity holder in publicly-traded company. Zhou: Incyte: Current Employment, Current equity holder in publicly-traded company. Assad: Incyte: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH