2023
Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer
Haddish‐Berhane N, Su Y, Russu A, Thayu M, Knoblauch R, Mehta J, Xie J, Gibbs E, Sun Y, Zhou H. Determination and Confirmation of Recommended Ph2 Dose of Amivantamab in Epidermal Growth Factor Receptor Exon 20 Insertion Non‐Small Cell Lung Cancer. Clinical Pharmacology & Therapeutics 2023, 115: 468-477. PMID: 37776107, DOI: 10.1002/cpt.3064.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdverse events of clinical interestEpidermal growth factor receptor-exonPopPK modelRecommended phase II dosePrimary efficacy end pointEGFR exon 20 insertionsPhase II doseExon 20 insertionsEfficacy end pointCovariates of clearanceVolume of distributionE-R relationshipSerum concentration dataEGFR ex20insII doseExposure-response analysesPlatinum chemotherapyExposure-responseEfficacy analysisPK variabilityPopulation PKAmivantamab
2022
Population pharmacokinetics and exposure–response analyses of daratumumab plus pomalidomide/dexamethasone in relapsed or refractory multiple myeloma
Dosne A, Li X, Luo M, Nnane I, Dimopoulos M, Terpos E, Sonneveld P, Kampfenkel T, Carson R, Amin H, Ruixo J, Zhou H, Sun Y, Xu Y. Population pharmacokinetics and exposure–response analyses of daratumumab plus pomalidomide/dexamethasone in relapsed or refractory multiple myeloma. British Journal Of Clinical Pharmacology 2022, 89: 1640-1655. PMID: 36484341, DOI: 10.1111/bcp.15628.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsExposure-response analysesPPK analysisPPK modelTwo-compartment PPK modelExposure to daratumumabProgression-free survivalNo dose adjustmentRefractory multiple myelomaExposure-responseTreatment of patientsClinically relevant effectsConcentration-time dataDaratumumab administrationDaratumumab exposureDaratumumab monotherapyDose adjustmentDosing regimenCharacterize pharmacokineticsMultiple myelomaPK samplingDaratumumabAdverse eventsPopulation pharmacokineticsPK exposure
2021
Population Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis
Luo M, Zhu P, Nnane I, Xiong Y, Merlini G, Comenzo R, Kastritis E, Wechalekar A, Weiss B, Tran N, Qin X, Vermeulen J, Sharma A, Sun Y, Zhou H. Population Pharmacokinetics and Exposure‐Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light‐Chain Amyloidosis. The Journal Of Clinical Pharmacology 2021, 62: 656-669. PMID: 34708423, DOI: 10.1002/jcph.1994.Peer-Reviewed Original ResearchConceptsLight chain amyloidosisSafety end pointSystemic exposureExposure-response analysesEnd pointsPopulation pharmacokineticsAmyloid light-chain amyloidosisNo dose adjustmentEfficacy end pointSystemic amyloid light-chain amyloidosisExposure-responseTreatment of light-chain amyloidosisImpact of potential covariatesLogistic regression analysisNonlinear mixed-effects modelingConcentration-time dataDexamethasone regimenDose adjustmentHematologic responseDaratumumabImmunogenicity dataPopPK analysisPopPK model
2020
Exposure‐Response and Population Pharmacokinetic Analyses of a Novel Subcutaneous Formulation of Daratumumab Administered to Multiple Myeloma Patients
Luo M, Usmani S, Mateos M, Nahi H, Chari A, San‐Miguel J, Touzeau C, Suzuki K, Kaiser M, Carson R, Heuck C, Qi M, Zhou H, Sun Y, Parasrampuria D. Exposure‐Response and Population Pharmacokinetic Analyses of a Novel Subcutaneous Formulation of Daratumumab Administered to Multiple Myeloma Patients. The Journal Of Clinical Pharmacology 2020, 61: 614-627. PMID: 33145788, PMCID: PMC8048619, DOI: 10.1002/jcph.1771.Peer-Reviewed Original ResearchConceptsSubcutaneous formulation of daratumumabIncidence of neutropeniaIntravenous daratumumabMonotherapy studiesCombination therapySubcutaneous daratumumabPK samplingStandard-of-care regimensPeak-to-trough fluctuationHigher trough concentrationsCombination therapy studiesSafety end pointMultiple myeloma patientsPopulation pharmacokinetic analysisCycle 1Flat doseExposure-response analysesMyeloma patientsDaratumumabTrough concentrationsSubcutaneous formulationPharmacokinetic analysisTreatment periodTherapy studiesNeutropenia
2019
Daratumumab (DARA) Subcutaneous (SC) Delivery in Relapsed or Refractory Multiple Myeloma (RRMM): Population Pharmacokinetics (PPK) and Exposure-Response (E-R) Analysis
Luo M, Parasrampuria D, Usmani S, Mateos M, Nahi H, Heuck C, Qi M, Sun S, Clemens P, Zhou H, Sun Y, Xu S. Daratumumab (DARA) Subcutaneous (SC) Delivery in Relapsed or Refractory Multiple Myeloma (RRMM): Population Pharmacokinetics (PPK) and Exposure-Response (E-R) Analysis. Blood 2019, 134: 3151. DOI: 10.1182/blood-2019-123405.Peer-Reviewed Original ResearchRefractory multiple myelomaEntity's Board of DirectorsStandard-of-care regimensPeak-to-trough fluctuationMultiple myelomaPopulation pharmacokinetic analysisExposure-response analysesPopulation pharmacokineticsAdverse eventsWT subgroupsDARA SCBody wtsSafety endpointsLower peak-to-trough fluctuationsRates of infusion-related reactionsSubgroup analysisSubcutaneous formulation of daratumumabTreatment of multiple myelomaNo dose adjustmentInfusion-related reactionsExposure-responseGeometric mean ratiosTreatment of MMSerum concentration-time dataCo-primary endpoints
2018
Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma
Xu X, Dimopoulos M, Sonneveld P, Ho P, Belch A, Leiba M, Capra M, Gomez D, Medvedova E, Iida S, Min C, Schecter J, Jansson R, Zhang L, Sun Y, Clemens P. Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma. Advances In Therapy 2018, 35: 1859-1872. PMID: 30374808, PMCID: PMC6223994, DOI: 10.1007/s12325-018-0815-9.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBortezomibDexamethasoneDose-Response Relationship, DrugFemaleFinlandHumansLenalidomideMaleMelphalanMiddle AgedMultiple MyelomaNeutropeniaProgression-Free SurvivalThalidomideTreatment OutcomeConceptsProgression-free survivalDaratumumab exposureCombination therapyDosing scheduleMultiple myelomaAdverse eventsMonoclonal antibody targeting CD38Standard-of-care regimensDose of daratumumabNo dose adjustmentCombination therapy regimensPopulation pharmacokinetic analysisExposure-safety relationshipMaximal clinical benefitDisease-related covariatesEfficacy/safety outcomesIntravenous daratumumabResultsPharmacokinetic profilesExposure-response analysesDose adjustmentTherapy regimensClinical benefitDaratumumabExposure-efficacyPivotal studies
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