2016
A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma
Holkova B, Zingone A, Kmieciak M, Bose P, Badros AZ, Voorhees PM, Baz R, Korde N, Lin HY, Chen JQ, Herrmann M, Xi L, Raffeld M, Zhao X, Wan W, Tombes MB, Shrader E, Weir-Wiggins C, Sankala H, Hogan KT, Doyle A, Annunziata CM, Wellons M, Roberts JD, Sullivan D, Landgren O, Grant S. A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma. Clinical Cancer Research 2016, 22: 1067-1075. PMID: 26446942, PMCID: PMC4775365, DOI: 10.1158/1078-0432.ccr-15-1076.Peer-Reviewed Original ResearchConceptsRefractory multiple myelomaPartial responseMultiple myelomaRelapsed/Refractory Multiple MyelomaMedian progression-free survival timeResponse rateProgression-free survival timeTwo-stage Simon designCommon grade 3Good partial responsePhase II studyPhase II trialMEK1/2 inhibitorSignificant preclinical activityMultiple myeloma cellsPrior therapyStable diseaseII trialClinical responseII studyProgressive diseaseMedian ageMean durationPreclinical activityDisease progression
2011
A Phase II Study of the MEK 1/2 Inhibitor AZD6244 (Selumetinib, ARRY-142866) in Relapsed or Refractory Multiple Myeloma
Holkova B, Badros A, Geller R, Voorhees P, Zingone A, Korde N, Lin H, Tombes M, Shrader E, Sankala H, Kmieciak M, Roberts J, Sullivan D, Landgren O, Grant S. A Phase II Study of the MEK 1/2 Inhibitor AZD6244 (Selumetinib, ARRY-142866) in Relapsed or Refractory Multiple Myeloma. Blood 2011, 118: 2931. DOI: 10.1182/blood.v118.21.2931.2931.Peer-Reviewed Original ResearchPhase II studyAspartate aminotransferaseRefractory MMII studyCommon treatment-related adverse eventsPresent phase II studyTreatment-related adverse eventsTwo-stage Simon designAcute kidney injuryCommon grade 3Objective partial responsePeripheral sensory neuropathyECOG performance scoreRefractory multiple myelomaFavorable clinical profilePre-clinical activityResponse/resistanceEffects of AZD6244Multiple myeloma cellsCompetitive small molecule inhibitorBone marrow microenvironmentPost-treatment expressionOrtho BiotechPrior regimensStable diseaseA Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-Cell Lymphoma
Holkova B, Perkins E, Sokol L, Richards K, Parekh S, Elstrom R, Badros A, Espinoza-Delgado I, Schell M, Kimball A, Tombes M, Shrader E, Sankala H, Coppola D, Kmieciak M, Sullivan D, Roberts J, Grant S. A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-Cell Lymphoma. Blood 2011, 118: 779. DOI: 10.1182/blood.v118.21.779.779.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaRefractory diffuse large B-cell lymphomaMantle cell lymphomaLarge B-cell lymphomaB-cell lymphomaResponse rateCohort BCohort ACell lymphomaDay 1Common treatment-related adverse eventsPan-HDAC inhibitor vorinostatTreatment-related adverse eventsCommon grade 3Peripheral sensory neuropathyPhase II studySpeakers bureauECOG performance scorePhase II trialSchedule of administrationPhase I studiesCombination of bortezomibNumerous preclinical studiesB-cell malignanciesProteasome inhibitor bortezomib