2009
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors
LoRusso P, Markman B, Tabernero J, Shazer R, Nguyen L, Heath E, Patnaik A, Papadopoulos K. A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3502-3502. DOI: 10.1200/jco.2009.27.15_suppl.3502.Peer-Reviewed Original ResearchAdverse eventsPhase I dose-escalation studyI dose-escalation studyDurable stable diseaseElevated hepatic transaminasesFood-induced increaseElevated liver enzymesNausea/vomitingSerious adverse eventsAdvanced solid tumorsDose-escalation studyPI3K pathway inhibitionClass I PI3K isoformsTumor growth inhibitionPI3K pathwayPharmacodynamic modulationQD regimenStable diseaseBID regimenHepatic transaminasesNeurological complaintsRepeat dosingPI3K isoformsPlasma insulinTolerable doses
2006
A phase I study of a novel spectrum selective kinase inhibitor (SSKI), XL880, administered orally in patients (pts) with advanced solid tumors (STs)
Eder J, Appleman L, Heath E, Malburg L, Zhu A, Pilat M, Shapiro G, Lorusso P. A phase I study of a novel spectrum selective kinase inhibitor (SSKI), XL880, administered orally in patients (pts) with advanced solid tumors (STs). Journal Of Clinical Oncology 2006, 24: 3041-3041. DOI: 10.1200/jco.2006.24.18_suppl.3041.Peer-Reviewed Original ResearchConsecutive daily dosesAdvanced solid tumorsDaily dosesSolid tumorsSingle doseReceptor tyrosine kinasesSmall-molecule MET inhibitorTerminal half-life valuesGrade 2 hypertensionPapillary renal cell carcinomaSystemic drug exposurePeak plasma levelsRenal cell carcinomaTumor-associated vasculatureHepatocyte growth factor receptorGrowth factor receptorPharmacokinetic samplingPK samplingPartial responseRepeat dosingCell carcinomaMinor responsePlasma levelsDrug exposureMET inhibitors