Abstract CT253: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Parsaclisib Plus Ruxolitinib in Patients with Myelofibrosis Who Have Suboptimal Response to Ruxolitinib
Authors: Yacoub Abdulraheem , Stouffs Michael , Zhou Feng , Assad Albert 
Published: July 2021

Abstract
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). 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 &lt;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 &lt;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. Upon patient completion of 24 weeks of treatment, he/she will be unblinded and if randomized to ruxolitinib plus placebo and 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.
Citation Format: Abdulraheem Yacoub, Michael Stouffs, Feng Zhou, Albert Assad. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Parsaclisib Plus Ruxolitinib in Patients with Myelofibrosis Who Have Suboptimal Response to Ruxolitinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT253.