2019
Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Schiller G, Lin T, Becker P, Patel P, Wang E, Spira A, Tsai M, Ridinger M, Croucher P, Erlander M, Silberman S. Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 230. DOI: 10.1182/blood-2019-126262.Peer-Reviewed Original ResearchPositive ptsBiomarker positivityPhase 1bBristol-Myers SquibbSpeakers bureauObjective responseCount recoveryPreliminary efficacyBlood samplesNegative groupRelapsed/Refractory Acute Myeloid LeukemiaADC therapeuticsDay 1Jazz PharmaceuticalsRefractory acute myeloid leukemiaBoehringer IngelheimDaiichi SankyoIncomplete count recoveryPhase 1b/2 studyPreclinical AML modelsSubset of ptsLow-dose cytarabinePredictive gene expression signaturesDose-escalation trialPlatelet count recovery1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib
Zeidan A, Becker P, Patel P, Schiller G, Tsai M, Lin T, Wang E, Erlander M, Cortes J. 1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib. Annals Of Oncology 2019, 30: v435. DOI: 10.1093/annonc/mdz251.001.Peer-Reviewed Original ResearchTarget engagementEvaluable ptsHigh dosesRefractory acute myeloid leukemiaInhibition of PLK1CR/CRiLow-dose cytarabinePreclinical AML modelsR AML patientsDose-escalation phasePolo-like kinase 1Anti-leukaemic activityAcute myeloid leukemiaEvaluable patientsLDAC armBM blastsDose escalationAML patientsPolo-like kinase 1 inhibitorsEscalation phaseBiomarker statusMyeloid leukemiaSelective PLK1 inhibitorBlood samplesHigh dose
2018
Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)
Zeidan A, Schiller G, Spira A, Patel P, Tsai M, Ridinger M, Silberman S, Erlander M, Cortes J. Preliminary Safety, Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the Polo-like Kinase-1 (PLK1) Inhibitor PCM-075, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (D) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML). Blood 2018, 132: 4043. DOI: 10.1182/blood-2018-99-112590.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLPhase 1 trialAdverse eventsPLK1 inhibitionBlast cellsPK profilesNon-hematologic adverse eventsPrevious phase 1 trialRandomized phase 2 studyStandard dose-escalation designRefractory acute myeloid leukemiaBM blast cellsGrade 1 fatigueGrade 1 nauseaPreclinical AML modelsTreatment-related deathsLow-dose cytarabinePhase 2 studySerious adverse eventsSpeakers bureauDose-escalation trialFurther dose escalationPhase 3 studyDose-escalation design