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 recovery
2019
Clinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study
Uy G, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Esteve J, Buchholz T, Couto S, Fan J, Hanna B, Li L, Pierce D, Hege K, Pourdehnad M, Zeidan A. Clinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study. Blood 2019, 134: 232. DOI: 10.1182/blood-2019-123966.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsCereblon E3 ligase modulatorSystemic inflammatory response syndromeCC-90009Phase 1 studyR AMLHighest dose levelDose levelsCelgene CorporationDaiichi SankyoSpeakers bureauGrade 3/4 treatment-emergent adverse eventsDay 1Jazz PharmaceuticalsObserved treatment-emergent adverse eventOpen-label phase 1 studySerious treatment-emergent adverse eventsHyperglycemic hyperosmolar nonketotic syndromeIncomplete blood count recoveryMorphologic leukemia-free stateRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeAdvisory CommitteeAntileukemic activityI Dose-Finding StudyPharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
Fan J, Wang H, Couto S, Yao T, Uy G, Zeidan A, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Buchholz T, Pourdehnad M, Pierce D. Pharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 2547. DOI: 10.1182/blood-2019-124291.Peer-Reviewed Original ResearchNovel cereblon E3 ligase modulatorCereblon E3 ligase modulatorPeripheral blood mononuclear cellsCC-90009T cellsPharmacodynamic responseCelgene CorporationDaiichi SankyoSpeakers bureauR AMLAML blastsIntegrated stress responseBlast cellsDay 1Dose levelsPhase I dose-escalation studyRefractory acute myeloid leukemiaI dose-escalation studyAdvisory CommitteeBone marrow core biopsiesAntileukemic activitySeattle GeneticsPhase IHigh-dose cohortNorwegian Cancer Society