Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clinical Cancer Research 2020, 26: 1247-1257. PMID: 31527168, PMCID: PMC7528620, DOI: 10.1158/1078-0432.ccr-18-4071.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade treatment-related adverse eventsTreatment-related adverse eventsAdequate organ functionHigh interpatient variabilityFavorable PK profileOptimal dosing schemePrimary endpointAdverse eventsOral clearancePartial responseComplete responsePhase 1/2Terminal eliminationTolerability studyPatient populationPharmacodynamic profileInterpatient variabilityDosing schemesDistinct pharmacokineticsTherapeutic indexOrgan functionPK profilesExtraterminal (BET) inhibitorsTarget inhibition