2023
A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors
Garralda E, Schram A, Bedard P, Schwartz G, Yuen E, McNeely S, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. The Oncologist 2023, 29: e131-e140. PMID: 37531083, PMCID: PMC10769797, DOI: 10.1093/oncolo/oyad215.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic AgentsAstheniaBayes TheoremCyclin-Dependent KinasesDose-Response Relationship, DrugFatigueHumansMaximum Tolerated DoseNeoplasmsProtein Kinase InhibitorsConceptsTreatment-related adverse eventsAdvanced solid tumorsCyclin-dependent kinase 7Adverse eventsSolid tumorsPhase I dose-escalation studyI dose-escalation studyLimited clinical activityGastrointestinal adverse eventsDose-escalation studyDose-limiting toxicityPhase I trialBest overall responsePeak-trough fluctuationKinase 7Common toxicitiesStable diseaseAbdominal painPrimary endpointSecondary endpointsAdult patientsPartial responseComplete responseI trialMedian time
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
2019
Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, LoRusso P, Hamid O, Janku F, Kittaneh M, Catenacci DVT, Chan E, Bekaii-Saab T, Gadgeel S, Loberg RD, Amore BM, Hwang YC, Tang R, Ngarmchamnanrith G, Kwak EL. Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 2403-2413. PMID: 30425090, PMCID: PMC6892342, DOI: 10.1158/1078-0432.ccr-18-1341.Peer-Reviewed Original ResearchMeSH KeywordsHumansMaximum Tolerated DoseNeoplasmsProtein Kinase InhibitorsPyridonesTreatment OutcomeTriazolesConceptsTreatment-related adverse eventsAdvanced solid tumorsAMG 337Adverse eventsFrequent treatment-related adverse eventsResponse rateSolid tumorsOpen-label phase ISmall-molecule MET inhibitorDose-escalation cohortsObjective response ratePhase II dosePromising response ratesDose-limiting toxicityMaximum plasma concentrationTumors warrants further investigationWarrants further investigationManageable toxicityDose expansionPrimary endpointSecondary endpointsDaily dosingMedian durationClinical responseMET inhibitors
2016
Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity
Schwartz GK, Dickson MA, LoRusso P, Sausville EA, Maekawa Y, Watanabe Y, Kashima N, Nakashima D, Akinaga S. Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity. Cancer Science 2016, 107: 499-506. PMID: 26850678, PMCID: PMC4832855, DOI: 10.1111/cas.12906.Peer-Reviewed Original ResearchConceptsOral tyrosine kinase inhibitorTyrosine kinase inhibitorsIGF-1RSolid tumorsHuman Phase I StudyInsulin-like growth factor receptor 1Colon carcinoma xenograft modelKinase inhibitorsHuman epidermal growth factor receptorPhase I clinical trialDose of KWModest antitumor activityAdvanced solid tumorsMetastatic breast cancerPhase I studiesGrowth factor receptor 1Human IGF-1RHuman malignant cell linesEpidermal growth factor receptorFactor receptor 1Inhibitory activityEvaluable patientsGrowth factor receptorMalignant cell linesStable disease