Contributions
Abstract: PB1715
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
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.
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 aged ≥18 years with a diagnosis of at least INT-1–risk (according to the Dynamic International Prognostic Scoring System [DIPSS]; Passamonti F, et al. Blood. 2010;115(9):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 North America, Europe, Asia, and Oceania.
Results
Not applicable
Conclusion
Not applicable
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Myeloproliferative disorder, PI3K
Abstract: PB1715
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
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.
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 aged ≥18 years with a diagnosis of at least INT-1–risk (according to the Dynamic International Prognostic Scoring System [DIPSS]; Passamonti F, et al. Blood. 2010;115(9):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 North America, Europe, Asia, and Oceania.
Results
Not applicable
Conclusion
Not applicable
Keyword(s): Janus Kinase inhibitor, Myelofibrosis, Myeloproliferative disorder, PI3K