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 recoveryAML-207: Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia: Effects on Marrow Recovery and Transfusion Independence
Zeidan A, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Ma W, Zeremski M, Kudla A, Chan G, Sekeres M. AML-207: Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia: Effects on Marrow Recovery and Transfusion Independence. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s191-s192. DOI: 10.1016/s2152-2650(20)30733-3.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeAbsolute neutrophil countChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeEvaluable patientsIntensive chemotherapyMedian durationTransfusion independenceMarrow recoveryHematopoietic recoveryMyeloid leukemiaMyelomonocytic leukemiaEarly marrow recoveryEarly platelet recoveryUp-front treatmentManageable safety profileOpen-label studyRate of transfusionMain outcome measuresEarly hematopoietic recoveryCycle 1Cycle 2Dose delaysPartial remission
2019
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
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