Therapy Detail

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Therapy Name Pacritinib
Synonyms
Therapy Description

Vonjo (pacritinib) is an inhibitor of JAK2 and FLT3, with activity against JAK2 V617F and FLT3 ITD, which potentially increases tumor cell apoptosis, induces cell cycle arrest, and decreases tumor growth (PMID: 22829080, PMID: 21691275). Vonjo (pacritinib) is FDA approved for use in patients with primary or secondary myelofibrosis (FDA.gov).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Pacritinib Vonjo SB1518|SB-1518|SB 1518 FLT3 Inhibitor 65 JAK2 Inhibitor - ATP competitive 15 Vonjo (pacritinib) is an inhibitor of JAK2 and FLT3, with activity against JAK2 V617F and FLT3 ITD, which potentially increases tumor cell apoptosis, induces cell cycle arrest, and decreases tumor growth (PMID: 22829080, PMID: 21691275). Vonjo (pacritinib) is FDA approved for use in patients with primary or secondary myelofibrosis (FDA.gov).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 Y842H hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 Y842H demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited kinase activity, phosphorylation of Flt3 and Stat5, and viability in a transformed cell line expressing a FLT3-ITD mutation in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D839G hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D839G demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in a transformed cell line expressing a FLT3-ITD mutation and FLT3 D835H in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins JAK2 V617F hematologic cancer predicted - sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) treatment decreased cell proliferation and downstream signaling in transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture but may not be capable of fully inhibiting Flt3 and Jak signaling at clinically achievable concentrations (PMID: 33149267). 33149267
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pacritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Vonjo (pacritinib) induced apoptosis and inhibited proliferation of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 22829080). 22829080
FLT3 exon 14 ins FLT3 F691L hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited phosphorylation of Flt3 and Stat5 and viability in a transformed cell line expressing a FLT3-ITD mutation and FLT3 F691L in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 D835Y demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins JAK1 S703I hematologic cancer decreased response Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in an acute myeloid leukemia cell line harboring a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 31102119). 31102119
FLT3 D835H hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in a transformed cell line expressing FLT3 D835H in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins JAK3 V722I hematologic cancer decreased response Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). 33149267
FLT3 D835Y hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited kinase activity and viability in a transformed cell line expressing FLT3 D835Y in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835Y hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited phosphorylation of Flt3 and Stat5 and viability in a transformed cell line expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835Y hematologic cancer conflicting Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02251821 Phase II Fludarabine Tacrolimus Mycophenolate mofetil Busulfan Pacritinib Momelotinib Melphalan Methotrexate Ruxolitinib Cyclophosphamide JAK-2 Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis Active, not recruiting USA 0
NCT03601819 Phase I Pacritinib Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders Terminated USA 0
NCT02469415 Phase II Decitabine Azacitidine Pacritinib Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS) Terminated USA 0
NCT02277093 Phase II Pacritinib Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer Terminated USA 0
NCT04635059 Phase II Pacritinib Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer (BLAST) Active, not recruiting USA 0
NCT03165734 Phase II Lenalidomide Ruxolitinib Hydroxyurea Pacritinib Thalidomide A Phase 2/3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis (PACIFICA) Recruiting USA | ITA | GBR | FRA | ESP | DEU | CAN | AUS 13
NCT03645824 Phase II Pacritinib Myelofibrosis Treated With Pacritinib Before aSCT. (HOVON134MF) (HOVON134MF) Active, not recruiting BEL 1
NCT04858256 Phase II Pacritinib Pacritinib in Relapsed/Refractory T-cell Lymphoproliferative Neoplasms Recruiting USA 0


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