2023
Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia
Croucher P, Ridinger M, Becker P, Lin T, Silberman S, Wang E, Zeidan A. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Annals Of Hematology 2023, 102: 3049-3059. PMID: 37702821, PMCID: PMC10567832, DOI: 10.1007/s00277-023-05442-9.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AML patientsAML patientsMyeloid leukemiaRefractory (R/R) AMLRelapsed/refractory (R/R) AMLHigher CR/CRi ratesCR/CRi rateRefractory acute myeloid leukemiaGene signaturePhase 1b/2 studyPhase 1b/2 trialPhase 1b trialBone marrow blastsSF mutationsBone marrow samplesCRi rateComplete remissionMarrow blastsClinical responseCount recoveryInitial safetyMarrow samplesPotential therapyMolecular predictors
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recoveryMolecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine
Daigle S, Choe S, DiNardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Döhner H, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, De Botton S, Stone R, Frattini M, Franovic A, Xu E, Winkler T, Wu B, Vyas P. Molecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine. Blood 2020, 136: 49-51. DOI: 10.1182/blood-2020-136922.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsAcute myeloid leukemiaBone marrow mononuclear cellsCurrent equity holderIntensive induction chemotherapyAgios PharmaceuticalsSafety monitoring boardIsocitrate dehydrogenase 1Daiichi SankyoSeattle GeneticsSpeakers bureauBristol-Myers SquibbIDH2 mutationsPTC TherapeuticsClinical responseMononuclear cellsClinical trialsDisease progressionMyeloid leukemiaMonitoring boardRefractory (R/R) AMLMutant IDH1R AMLAdvisory CommitteeForty-seven