2024
A first-in-human, phase 1, dose escalation study of SGR-2921 as monotherapy in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
Weiss D, Dinardo C, Strickland S, Skikne B, Zeidan A, Traer E, Carraway H, Carraway H, Frankel S, Wang J, Pirie-Shepherd S, Piccotti J, Wright D, Akinsanya K. A first-in-human, phase 1, dose escalation study of SGR-2921 as monotherapy in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. Journal Of Clinical Oncology 2024, 42: tps6590-tps6590. DOI: 10.1200/jco.2024.42.16_suppl.tps6590.Peer-Reviewed Original ResearchEastern Cooperative Oncology GroupCell line-derived xenograftsDose-escalation studyMaximum tolerated dosePatient-derived xenograftsHigh riskEscalation studyTreatment armsEffects of CYP3A4 inhibitionRecommended phase 2 doseRelapsed/refractory acute myeloid leukemiaPhase 2 doseAccelerated titration designMinichromosome maintenance protein 2Preliminary antitumor activityCooperative Oncology GroupFirst-in-humanAcute myeloid leukemiaGrade 2 eventsTreated patient populationTolerated dose levelsAML cell linesAnti-tumor activityInhibition of Cdc7Cancer cell death
2023
A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
DiNardo C, Strickland S, Skikne B, Zeidan A, Traer E, Carraway H, Frankel S, Weiss D, Wang J, Pirie-Shepherd S, Piccotti J, Wright D, Akinsanya K. A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Blood 2023, 142: 1548. DOI: 10.1182/blood-2023-186036.Peer-Reviewed Original ResearchR AMLAcute myeloid leukemiaRefractory acute myeloid leukemiaCell line-derived xenograftsDose-escalation studyMyelodysplastic syndromeCentral nervous systemDose levelsEscalation studyFirst doseTreatment armsMyeloid leukemiaEastern Cooperative Oncology Group performance statusRelapsed/Refractory Acute Myeloid LeukemiaPatient-derived xenograft AML modelHigh-risk myelodysplastic syndromeHigh unmet medical needAnimal models representativeMultiple prior linesPhase 2 doseSingle-patient cohortsTreatment arm ATreatment arm B.Antitumor activitySingle-dose pharmacokinetics
2022
A Phase 1/2 Study of the Oral Janus Kinase 1 Inhibitors INCB052793 and Itacitinib Alone or in Combination With Standard Therapies for Advanced Hematologic Malignancies
Zeidan AM, Cook RJ, Bordoni R, Berenson JR, Edenfield WJ, Mohan S, Zhou G, Asatiani E, Srinivas N, Savona MR. A Phase 1/2 Study of the Oral Janus Kinase 1 Inhibitors INCB052793 and Itacitinib Alone or in Combination With Standard Therapies for Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2022, 22: 523-534. PMID: 35260349, DOI: 10.1016/j.clml.2022.01.012.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaPhase 1/2 studyAdvanced hematologic malignanciesMyelodysplastic syndromeHematologic malignanciesObjective responseStandard therapyRefractory acute myeloid leukemiaPhase 2 doseObjective response rateRefractory multiple myelomaPhase 2Lack of efficacyInhibition of JAK1Janus kinasePhase 1Primary endpointTreatment discontinuationAdverse eventsProgressive diseaseDose escalationStudy treatmentMultiple myelomaMyeloid leukemiaDNA methyltransferase inhibitorPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2019
A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Pollyea D, Garcia J, Brunner A, Roncolato F, Borate U, Odenike O, Bajel A, Watson A, Götze K, Nolte F, Tan P, Hong W, Dunbar M, Zhou Y, Gressick L, Ainsworth W, Harb J, Salem A, Hayslip J, Swords R, Garcia-Manero G. A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome. Blood 2019, 134: 565. DOI: 10.1182/blood-2019-124994.Peer-Reviewed Original ResearchStock/stock optionsTreatment-emergent adverse eventsProgression-free survivalMedian progression-free survivalAbbVie IncOverall survivalFebrile neutropeniaStable diseaseMarrow blastsMyelodysplastic syndromeBcl-2 inhibitorsAstra ZenecaFrequent treatment-emergent adverse eventsInternational Working Group 2006 criteriaSerious treatment-emergent adverse eventsAllogeneic stem cell transplantationAdvisory CommitteeDaiichi SankyoCycles of AZACycles of decitabineECOG performance statusPhase 1b studyPhase 2 dosePredominant grade 3Refractory myelodysplastic syndrome