2023
Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma
Grommes C, Nowakowski G, Rosenthal A, Lunning M, Ramchandren R, Regales L, Fowle M, Lane M, Wang C, Omuro A, Leslie L, Soussain C, Dabrowska-Iwanicka A, Ferreri A, Tun H. Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma. Blood 2023, 142: 3143. DOI: 10.1182/blood-2023-190391.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaInterleukin-1 receptor-associated kinase 4FMS-like tyrosine kinase 3Toll-like receptorsExpansion cohortPCNSL patientsDisease progressionRefractory primary central nervous system lymphomaDiagnosis of PCNSLCentral nervous system lymphomaPathogenesis of PCNSLSafety/tolerabilityOpen-label trialBlood-brain barrier penetrationPrimary CNS lymphomaSufficient blood-brain barrier penetrationNervous system lymphomaInitial clinical dataKey inclusion criteriaPotent oral inhibitorCentral nervous systemBrain barrier penetrationPK/PDTyrosine kinase 3Further preclinical studiesTakeaim Lymphoma: An Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Combination with Ibrutinib in Patients with Relapsed or Refractory Hematologic Malignancies
Grommes C, Tun H, Rosenthal A, Lunning M, Ramchandren R, Regales L, Zhao W, Lane M, Wang C, von Roemeling R, Isufi I, Leslie L, Nowakowski G. Takeaim Lymphoma: An Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Combination with Ibrutinib in Patients with Relapsed or Refractory Hematologic Malignancies. Blood 2023, 142: 4497. DOI: 10.1182/blood-2023-189746.Peer-Reviewed Original ResearchInterleukin-1 receptor-associated kinase 4Non-Hodgkin lymphomaFMS-like tyrosine kinase 3Bid dose levelToll-like receptorsDose escalationBTK inhibitorsNHL patientsDose levelsAcceptable long-term safety profileRefractory non-Hodgkin lymphomaLong-term safety profileB-cell non-Hodgkin lymphomaBruton tyrosine kinase inhibitorsBTK inhibitor resistanceContinuous oral dosingMurine PDX modelPhase 2 doseRelapsed/Refractory Non-Hodgkin LymphomaMedian treatment durationOpen-label trialRefractory hematologic malignanciesBlood-brain barrierPreliminary efficacy dataNovel oral inhibitor
2022
Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations
Choudhary GS, Pellagatti A, Agianian B, Smith MA, Bhagat TD, Gordon-Mitchell S, Sahu S, Pandey S, Shah N, Aluri S, Aggarwal R, Aminov S, Schwartz L, Steeples V, Booher RN, Ramachandra M, Samson M, Carbajal M, Pradhan K, Bowman TV, Pillai MM, Will B, Wickrema A, Shastri A, Bradley RK, Martell RE, Steidl UG, Gavathiotis E, Boultwood J, Starczynowski DT, Verma A. Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations. ELife 2022, 11: e78136. PMID: 36040792, PMCID: PMC9427103, DOI: 10.7554/elife.78136.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeNF-kB activationLymphoma SocietyMDS/acute myeloid leukemiaNational InstitutePathogenesis of MDSInterleukin-1 receptor-associated kinase 4Expression of IRAK4Inflammatory-immune pathwaysInflammatory cytokine productionSpecific oncogenic pathwaysCareer development grantsHealth research trainingCritical downstream mediatorCytokine productionMyeloid leukemiaPreclinical modelsNew York State DepartmentXenograft modelImmune pathwaysNF-kB.MDS samplesTRAF6 activationLeukemic growth
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