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
2018
A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors
Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach J, Kapoun A, Xu L, Munster P. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Annals Of Oncology 2018, 29: 1561-1568. PMID: 29726923, DOI: 10.1093/annonc/mdy171.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCohort StudiesDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasmsPrognosisReceptor, Notch1Salvage TherapySurvival RateTissue DistributionConceptsNotch1 pathway activationPartial responseSolid tumorsPathway activationAdverse eventsCommon drug-related adverse eventsDrug-related adverse eventsDose-expansion studyGrade 3 diarrheaGrade 3 fatigueUnconfirmed partial responseRefractory solid tumorsProlonged SDsDisease stabilizationExpansion cohortMain toxicityRECIST 1.1Dose escalationEfficacy signalsClinical benefitPharmacodynamic effectsPreliminary efficacyAssessable subjectsImmunohistochemistry assaysNonlinear pharmacokinetics