2024
Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies
Bewersdorf J, Mi X, Lu B, Kuykendall A, Sallman D, Patel M, Stevens D, Philipovskiy A, Sutamtewagul G, Masarova L, Keiffer G, Verma A, Bhagwat N, Heiser D, Ro S, Hong W, Abdel-Wahab O, Stein E. Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies. Blood 2024, 144: 3215. DOI: 10.1182/blood-2024-198495.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsPlatelet transfusion independenceProtein arginine methyltransferase 5Myeloid malignanciesSplicing factor mutationsSymmetric dimethyl arginineMedian PFSTransfusion independenceFollow-upOpen-label phase Ib studyRed blood cell transfusion-dependentPRMT5 inhibitionAdequate end-organ functionBaseline serum EPO levelsRecommended phase 2 doseMedian duration of treatmentGrade 5 eventsLower-risk MDSMDS/MPN overlap syndromesPhase 2 doseIntensive induction chemotherapyPeripheral blood mononuclear cellsHigh-risk MDSPhase Ib studyMedian follow-up
2023
E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial
Bewersdorf J, Chandhok N, Watts J, Derkach A, Abdel-Wahab O, Stein E, Taylor J. E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial. Blood 2023, 142: 1547. DOI: 10.1182/blood-2023-182369.Peer-Reviewed Original ResearchAcute myeloid leukemiaEastern Cooperative Oncology GroupPhase II clinical trialChronic myelomonocytic leukemiaMyelodysplastic syndromePatient-derived xenograftsII clinical trialsPreclinical dataSplicing factor genesMyeloid malignanciesClinical trialsAdequate end-organ functionContext of combination therapyDay 1Safety run-in phaseRefractory acute myeloid leukemiaSimon 2-stage designResponse rateDynamic BH3 profilingCycles of therapyNegative prognostic impactEvent-free survivalMyelodysplastic syndrome patientsHuman acute myeloid leukemiaPhase II trial