2018
Activity of ramucirumab (R) with pembrolizumab (P) by PD-L1 expression in advanced solid tumors: Phase 1a/b study in later lines of therapy.
Herbst R, Chau I, Petrylak D, Arkenau H, Bendell J, Santana-Davila R, Calvo E, Penel N, Martin-Liberal J, Soriano A, Cassier P, Krebs M, Isambert N, Widau R, Mi G, Jin J, Ferry D, Fuchs C, Paz-Ares L. Activity of ramucirumab (R) with pembrolizumab (P) by PD-L1 expression in advanced solid tumors: Phase 1a/b study in later lines of therapy. Journal Of Clinical Oncology 2018, 36: 3059-3059. DOI: 10.1200/jco.2018.36.15_suppl.3059.Peer-Reviewed Original Research
2013
Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours
Soria JC, Baselga J, Hanna N, Laurie SA, Bahleda R, Felip E, Calvo E, Armand JP, Shepherd FA, Harbison CT, Berman D, Park JS, Zhang S, Vakkalagadda B, Kurland JF, Pathak AK, Herbst RS. Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. European Journal Of Cancer 2013, 49: 1815-1824. PMID: 23490650, DOI: 10.1016/j.ejca.2013.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedArea Under CurveCarcinoma, Non-Small-Cell LungDiarrheaDose-Response Relationship, DrugDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideExanthemaFemaleHumansLung NeoplasmsMaleMetabolic Clearance RateMiddle AgedNeoplasm MetastasisNeoplasmsPiperidinesProtein Kinase InhibitorsPyrrolesQuinazolinesReceptor, ErbB-2Treatment OutcomeTriazinesVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-3ConceptsIIa studyBMS-690514Growth factor receptorPhase IAdverse eventsEGFR mutationsHER-2Phase IIaFrequent treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsOral tyrosine kinase inhibitorDisease controlVascular endothelial growth factor receptorManageable safety profileObjective response rateAdvanced solid tumorsFactor receptorMetastatic solid tumorsEndothelial growth factor receptorCell lung cancerTyrosine kinase inhibitorsInhibition of VEGFREpidermal growth factor receptorWild-type EGFR
2012
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposureA Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O'Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2012, 18: 4173-4182. PMID: 22693357, DOI: 10.1158/1078-0432.ccr-12-0714.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overArea Under CurveDiarrheaDisease ProgressionDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFatigueFemaleGonanesHumansMaleMetabolic Clearance RateMiddle AgedMutationNauseaNeoplasmsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsTreatment OutcomeVomitingConceptsDose-limiting toxicityArm 1PX-866Stable diseaseArm 2Frequent study drug-related adverse eventsSolid tumorsStudy drug-related adverse eventsDrug-related adverse eventsMulticenter phase I trialGrade III diarrheaAdvanced solid tumorsDose-escalation studyResponse Evaluation CriteriaContinuous dosing scheduleElevated aspartate aminotransferasePhase I trialEvaluable patientsIrreversible small-molecule inhibitorAdverse eventsDosing schedulesI trialAdditional patientsGastrointestinal disordersIncurable cancer
2011
A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors
Infante JR, Kurzrock R, Spratlin J, Burris HA, Eckhardt SG, Li J, Wu K, Skolnik JM, Hylander-Gans L, Osmukhina A, Huszar D, Herbst RS. A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors. Cancer Chemotherapy And Pharmacology 2011, 69: 165-172. PMID: 21638123, DOI: 10.1007/s00280-011-1667-z.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPrimary dose-limiting toxicityPhase IAcceptable safety profileAdvanced solid malignanciesAdvanced solid tumorsRelated adverse eventsSeverity of neutropeniaConclusionThe MTDAdverse eventsIntravenous infusionSafety profileSolid malignanciesAZD4877Intermediate doseDose reductionPart BPharmacokinetic profileDay 1Solid tumorsPart ANeutropeniaTolerabilityPatientsMTD
2010
A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors
Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L, Juan G, Hwang YC, Wong S, Hill JS, Friberg G, LoRusso PM. A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors. Clinical Cancer Research 2010, 16: 5883-5891. PMID: 20947515, DOI: 10.1158/1078-0432.ccr-10-0631.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced solid tumorsPartial responseColorectal cancerStable diseaseSolid tumorsPositron emission tomographic scansHuman death receptor 5Dose-expansion phaseGrade 3 eventsDose-escalation phaseCell lung cancerStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyDeath receptor 5Week 96Adult patientsAdverse eventsIntravenous dosesMore dosesTumor sizeLung cancerTumor levelsTumor responseFirst-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Burris H, Rodon J, Sharma S, Herbst R, Tabernero J, Infante J, Silva A, Demanse D, Hackl W, Baselga J. First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2010, 28: 3005-3005. DOI: 10.1200/jco.2010.28.15_suppl.3005.Peer-Reviewed Original Research
2009
Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors
Herbst RS, Hong D, Chap L, Kurzrock R, Jackson E, Silverman JM, Rasmussen E, Sun YN, Zhong D, Hwang YC, Evelhoch JL, Oliner JD, Le N, Rosen LS. Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2009, 27: 3557-3565. PMID: 19546406, DOI: 10.1200/jco.2008.19.6683.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAngiopoietinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticBevacizumabDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFatigueFemaleHumansInfusions, IntravenousMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsTreatment OutcomeConceptsAMG 386Advanced solid tumorsPartial responseAntitumor activitySolid tumorsElimination half-life valuesPatients 48 hoursMaximum-tolerated doseTreatment-related toxicityDose-limiting toxicityRefractory ovarian cancerWeeks of treatmentPeptide-Fc fusion proteinVolume transfer constantAngiopoietin inhibitorsCommon toxicitiesStable diseasePeripheral edemaAdult patientsClinical sequelaeMethods PatientsWeekly dosesTumor burdenRespiratory arrestSafety profile
2008
Phase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer
Bahleda R, Felip E, Herbst R, Hanna N, Laurie S, Shepherd F, Armand J, Sweeney C, Calvo-Aller E, Soria J. Phase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer. Journal Of Clinical Oncology 2008, 26: 2564-2564. DOI: 10.1200/jco.2008.26.15_suppl.2564.Peer-Reviewed Original Research
2007
First-in-human study of AMG 386, a selective angiopoietin1/2-neutralizing peptibody, in adult patients with advanced solid tumors
Rosen L, Hong D, Chap L, Kurzrock R, Garcia A, Rasmussen E, Nguyen L, Hwang Y, Storgard C, Herbst R. First-in-human study of AMG 386, a selective angiopoietin1/2-neutralizing peptibody, in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2007, 25: 3522-3522. DOI: 10.1200/jco.2007.25.18_suppl.3522.Peer-Reviewed Original ResearchAMG 386Advanced solid tumorsAdverse eventsStable diseaseTumor responseHuman studiesGrade 2Solid tumorsDCE-MRIMinor clinical responseSignificant vascular effectsSerum CA 125Treatment-related toxicityDose-limiting toxicityFurther clinical studiesEvaluable patientsEvaluable subjectsPeripheral edemaRECIST criteriaAdult patientsClinical responseProgressive diseaseWeekly administrationVascular effectsCA 125First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors
LoRusso P, Hong D, Heath E, Kurzrock R, Wang D, Hsu M, Goyal L, Wiezorek J, Storgard C, Herbst R. First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2007, 25: 3534-3534. DOI: 10.1200/jco.2007.25.18_suppl.3534.Peer-Reviewed Original ResearchNon-small cell lung cancerMetabolic partial responseAdvanced solid tumorsPartial responseStable diseaseColorectal cancerHuman studiesSolid tumorsMaximum standardized uptake valueDose-linear kineticsElevated serum lipaseSequential dose cohortsOnly grade 3Cell lung cancerReceptor 2 agonistStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyAnti-tumor activitySensitive tumor cellsTumor response dataSerious AEsDose cohortsProgressive diseaseUnacceptable toxicitySafety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors
Rosen LS, Kurzrock R, Mulay M, Van Vugt A, Purdom M, Ng C, Silverman J, Koutsoukos A, Sun YN, Bass MB, Xu RY, Polverino A, Wiezorek JS, Chang DD, Benjamin R, Herbst RS. Safety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2007, 25: 2369-2376. PMID: 17557949, DOI: 10.1200/jco.2006.07.8170.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseAMG 706Advanced solid tumorsSolid tumorsAdvanced refractory solid tumorsRefractory advanced solid tumorsVascular endothelial growth factor receptor 1Frequent adverse eventsRefractory solid tumorsDose-proportional mannerFactor receptorDose-finding studyOral multikinase inhibitorStudy of patientsPlacental growth factorGrowth factor receptor 1Platelet-derived growth factor receptorFactor receptor 1Stem cell factor receptorGrowth factor receptorStable diseaseKinase domain receptorAdverse eventsPartial responseProgressive disease
2006
A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer
Herbst R, Mendolson D, Ebbinghaus S, Gordon M, O’Dwyer P, Lieberman G, Ing J, Kurzrock R, Novotny W, Eckhardt G. A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer. Journal Of Clinical Oncology 2006, 24: 3013-3013. DOI: 10.1200/jco.2006.24.18_suppl.3013.Peer-Reviewed Original ResearchAdvanced solid tumorsLiver metastasesSolid tumorsHematologic malignanciesApo2L/TRAILRecombinant human Apo2L/TRAILPost-baseline tumour assessmentPhase I safetyObjective partial responseFurther dose optimizationAttributable toxicityStable diseaseAdult patientsI safetyPartial responseAdvanced cancerCommon diagnosisRandomized trialsStandard treatmentReceptor agonistOvarian cancerPreclinical modelsSafety dataTumor assessmentMost normal cells
2005
Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results
Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results. Journal Of Clinical Oncology 2005, 23: 5474-5483. PMID: 16027439, DOI: 10.1200/jco.2005.04.192.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsAG-013736Clinical activityOral receptor tyrosine kinase inhibitorSolid tumorsReceptor tyrosine kinase inhibitorsGrowth factorSingle test dosesMaximum-tolerated dosePhase II doseDose-limiting toxicitySignificant drug interactionsPeak plasma concentrationEndothelial cell growth factorPhase II testingVascular endothelial cell growth factorTyrosine kinase inhibitorsHighest dose levelPlatelet-derived growth factorIndividual PK parametersEffect of foodCell growth factorObserved hypertensionDrug holidayPartial responseDynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study
Liu G, Rugo HS, Wilding G, McShane TM, Evelhoch JL, Ng C, Jackson E, Kelcz F, Yeh BM, Lee FT, Charnsangavej C, Park JW, Ashton EA, Steinfeldt HM, Pithavala YK, Reich SD, Herbst RS. Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study. Journal Of Clinical Oncology 2005, 23: 5464-5473. PMID: 16027440, DOI: 10.1200/jco.2005.04.143.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsAG-013736Vascular responsesMagnetic resonance imagingAcute dosingDay 2Solid tumorsAngiogenesis inhibitorsResonance imagingContrast-enhanced magnetic resonance imagingOral angiogenesis inhibitorSchedule of therapyTumor vascular functionDynamic contrast-enhanced magnetic resonance imagingObjective disease responsePhase II testingDCE-MRI scansEffect of treatmentTumor vascular parametersVolume transfer constantMorning doseSuitable markerPharmacodynamic measuresVascular functionPharmacodynamic response
2004
151 AMG 706 first in human, open-label, dose-finding study evaluating the safety and pharmacokinetics (PK) in subjects with advanced solid tumors
Herbst R, Kurzrock R, Parson M, Benjamin R, Chen L, Ng C, Ingram M, Wong S, Chang D, Rosen L. 151 AMG 706 first in human, open-label, dose-finding study evaluating the safety and pharmacokinetics (PK) in subjects with advanced solid tumors. European Journal Of Cancer Supplements 2004, 2: 48. DOI: 10.1016/s1359-6349(04)80159-9.Peer-Reviewed Original ResearchClinical and dynamic imaging results of the first phase I study of AG–013736, an oral anti-angiogenesis agent, in patients (pts) with advanced solid tumors
Rugo H, Herbst R, Liu G, Park J, Kies M, Pithavala Y, McShane T, Steinfeldt H, Reich S, Wilding G. Clinical and dynamic imaging results of the first phase I study of AG–013736, an oral anti-angiogenesis agent, in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2004, 22: 2503-2503. DOI: 10.1200/jco.2004.22.14_suppl.2503.Peer-Reviewed Original ResearchClinical and dynamic imaging results of the first phase I study of AG–013736, an oral anti-angiogenesis agent, in patients (pts) with advanced solid tumors
Rugo H, Herbst R, Liu G, Park J, Kies M, Pithavala Y, McShane T, Steinfeldt H, Reich S, Wilding G. Clinical and dynamic imaging results of the first phase I study of AG–013736, an oral anti-angiogenesis agent, in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2004, 22: 2503-2503. DOI: 10.1200/jco.2004.22.90140.2503.Peer-Reviewed Original Research
2002
Phase I study of recombinant human endostatin in patients with advanced solid tumors.
Herbst RS, Hess KR, Tran HT, Tseng JE, Mullani NA, Charnsangavej C, Madden T, Davis DW, McConkey DJ, O’Reilly M, Ellis LM, Pluda J, Hong WK, Abbruzzese JL. Phase I study of recombinant human endostatin in patients with advanced solid tumors. Journal Of Clinical Oncology 2002, 20: 3792-803. PMID: 12228199, DOI: 10.1200/jco.2002.11.061.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsCollagenCollagen Type XVIIIEndostatinsEndothelial Growth FactorsE-SelectinFemaleFibroblast Growth Factor 2Hematologic DiseasesHumansImmunoglobulinsInfusions, IntravenousLymphokinesMagnetic Resonance ImagingMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPeptide FragmentsRecombinant ProteinsTime FactorsTissue DistributionVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsRh-EndoConcentration-time curveRecombinant human endostatinSerum markersPreclinical modelsSolid tumorsHuman endostatinDose-limiting toxic effectAntitumor activityTwo-compartmental open modelAdvanced solid tumorsPhase I trialCentral line accessDose-finding trialMinor antitumor activityI trialIntravenous bolusSerum biomarkersSerum antibodiesPharmacokinetic dispositionAllergic reactionsPatientsPharmacokinetic profileDose levelsPhase I