2020
A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2012
A first-in-human phase Ib study to evaluate the MEK inhibitor GDC-0973, combined with the pan-PI3K inhibitor GDC-0941, in patients with advanced solid tumors.
LoRusso P, Shapiro G, Pandya S, Kwak E, Jones C, Belvin M, Musib L, de Crespigny A, McKenzie M, Gates M, Chan I, Bendell J. A first-in-human phase Ib study to evaluate the MEK inhibitor GDC-0973, combined with the pan-PI3K inhibitor GDC-0941, in patients with advanced solid tumors. Journal Of Clinical Oncology 2012, 30: 2566-2566. DOI: 10.1200/jco.2012.30.15_suppl.2566.Peer-Reviewed Original ResearchAdvanced solid tumorsPan-PI3K inhibitor GDCPhase Ib dose-escalation studySolid tumorsDays on/7 daysPartial metabolic responsePlasma PK samplesStudy drug combinationsDose-escalation studyInhibitor GDCPhase 1 trialRAS/RAF/MEKAnti-tumor activityClass I PI3K inhibitorPharmacokinetics of GDCPI3K/AktPI3K inhibitorsEvaluable ptsStable diseaseAdverse eventsPartial responseCPK elevationDose escalationElevated CPKConcurrent administration