2013
Phase I, dose-escalation study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced solid tumors.
Adjei A, LoRusso P, Ribas A, Sosman J, Pavlick A, Dy G, Zhou X, Gangolli E, Walker R, Kneissl M, Faucette S, Neuwirth R, Bozon V. Phase I, dose-escalation study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2528-2528. DOI: 10.1200/jco.2013.31.15_suppl.2528.Peer-Reviewed Original ResearchAdvanced solid tumorsDrug-related AEsSolid tumorsAcneiform dermatitisTAK-733Creatine phosphokinase increaseECOG PS 0Oral MEK inhibitorDose-escalation studyDose-proportional mannerMean accumulation ratioPeripheral blood samplesAnti-tumor activitySteady-state exposurePower model analysisStable diseasePS 0Partial responseEvaluable tumorsPeripheral bloodPustular rashBlood samplesXenograft modelHuman studiesMaximal efficacy
2012
456P Multicenter, Dose-Escalation Study of the Investigational Drug Tak-733, An Oral Mek inhibitor, in Patients (PTS) with Advanced Solid Tumors: Preliminary Phase 1 Results
Adjei A, LoRusso P, Ribas A, Sosman J, Dy G, Chmielowski B, Lipman P, Zhou X, Gangolli E, Bozón V. 456P Multicenter, Dose-Escalation Study of the Investigational Drug Tak-733, An Oral Mek inhibitor, in Patients (PTS) with Advanced Solid Tumors: Preliminary Phase 1 Results. Annals Of Oncology 2012, 23: ix158. DOI: 10.1016/s0923-7534(20)33014-3.Peer-Reviewed Original ResearchDose-limiting toxicityDrug-related AEsAdvanced solid tumorsAnti-tumor activityTAK-733Solid tumorsECOG PS 0Oral MEK inhibitorDose-escalation studyMedian age 58Non-hematologic malignanciesPeripheral blood lymphocytesCycle 1Multiple xenograft modelsEvaluable ptsStable diseasePartial responsePS 0Dose escalationEvaluable tumorsAdvisory BoardBlood lymphocytesAge 58Blood samplesXenograft model
2009
A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors
Wagner A, Von Hoff D, LoRusso P, Tibes R, Mazina K, Ware J, Yan Y, Derynck M, Demetri G. A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3501-3501. DOI: 10.1200/jco.2009.27.15_suppl.3501.Peer-Reviewed Original ResearchDose-proportional increaseAnti-tumor activityDose levelsPK dataPan-PI3K inhibitor GDCSolid tumorsPhase ICA-125 responseDose escalation armDose-escalation cohortsDrug-related AEsGrade 1/2 nauseaPreliminary PK dataSingle-dose PKAdvanced solid tumorsTotal daily dosesFDG-PET uptakeSelective oral inhibitorSteady-state PKHuman phase IProstate cancer modelPotential signsBID armCancer ptsQD armPhase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265–102)
Hong D, LoRusso P, Kurzrock R, Maroun C, Mehran M, Drouin M, Martell R, Wheler J. Phase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265–102). Journal Of Clinical Oncology 2009, 27: e14516-e14516. DOI: 10.1200/jco.2009.27.15_suppl.e14516.Peer-Reviewed Original ResearchDose levelsSolid tumorsGrade 3 nonhematologic toxicityPhase IDrug-related AEsGrade 4 neutropeniaGrade 4 thrombocytopeniaAdvanced solid tumorsDrug-related toxicityTreatment of patientsDose-dependent increaseVariety of cancersEfficacious exposureNonhematologic toxicitySustained hypertensionAdvanced malignanciesEscalation studyFirst doseIntermittent administrationDisease progressionAvailable small moleculesPD markersXenograft modelPatientsDay 1