2020
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
2016
ACTR-10. PHASE 0 TRIAL OF AZD1775 IN FIRST-RECURRENCE GLIOBLASTOMA PATIENTS
Sanai N, Li J, Boerner J, Dhruv H, Berens M, LoRusso P. ACTR-10. PHASE 0 TRIAL OF AZD1775 IN FIRST-RECURRENCE GLIOBLASTOMA PATIENTS. Neuro-Oncology 2016, 18: vi3-vi3. DOI: 10.1093/neuonc/now212.009.Peer-Reviewed Original ResearchPhase 0 trialsInterindividual variabilityGlioblastoma patientsPhase II studyApparent oral clearanceGlomerular filtration ratePhase I trialCL/F.CL/FSparse blood samplingElimination rate constantAbsorption rate constantPD endpointsAdult patientsII studyOral clearanceI trialSingle doseDrug exposureFiltration ratePreclinical modelsPreclinical studiesGlioma patientsPlasma ratioBlood sampling