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 ResearchConceptsTreatment-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 timeFirst-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan A, Wu Y, Martin P, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Patel S. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunology, Immunotherapy 2023, 72: 2443-2458. PMID: 37016126, PMCID: PMC10264501, DOI: 10.1007/s00262-023-03430-6.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPancreatic ductal adenocarcinomaColorectal cancerExpansion cohortHuman studiesResponse rateAnti-CD73 monoclonal antibodyProgression-free survival ratesTumor cellsMonoclonal antibodiesCommon being fatigueManageable safety profileObjective response rateAdvanced colorectal cancerAdvanced solid tumorsCell lung cancerPeripheral T cellsDate of registrationCD73 enzymatic activityAdverse eventsEscalation cohortsLocal immunosuppressionCD73 expressionSafety profileLung cancer
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
2010
A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors
Heath E, Chiorean E, Sweeney C, Hodge J, Lager J, Forman K, Malburg L, Arumugham T, Dar M, Suttle A, Gainer S, LoRusso P. A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors. Clinical Pharmacology & Therapeutics 2010, 88: 818-823. PMID: 20980999, DOI: 10.1038/clpt.2010.199.Peer-Reviewed Original ResearchConceptsHigh-fat mealAdvanced solid tumorsGrowth factor receptorSolid tumorsMaximum observed plasma concentrationPlasma concentration-time curvePhase IAdministration of pazopanibOral angiogenesis inhibitorVascular endothelial growth factor receptorFactor receptorEndothelial growth factor receptorLow-fat mealObserved plasma concentrationConcentration-time curvePlatelet-derived growth factor receptorDaily pazopanibOral pazopanibSafety profileSystemic exposureSingle doseSingle dosesPlasma concentrationsPazopanibFasted condition