2018
Final Results of a Phase I Prospective Trial Evaluating the Combination of Stereotactic Body Radiation Therapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma
Campbell A, Herbst R, Gettinger S, Goldberg S, Kluger H, Chiang A, Lilenbaum R, Schalper K, Sowell R, Kaech S, Decker R. Final Results of a Phase I Prospective Trial Evaluating the Combination of Stereotactic Body Radiation Therapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: s18-s19. DOI: 10.1016/j.ijrobp.2018.06.134.Peer-Reviewed Original ResearchSafety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study
Horn L, Gettinger SN, Gordon MS, Herbst RS, Gandhi L, Felip E, Sequist LV, Spigel DR, Antonia SJ, Balmanoukian A, Cassier PA, Liu B, Kowanetz M, O'Hear C, Fassò M, Grossman W, Sandler A, Soria JC. Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. European Journal Of Cancer 2018, 101: 201-209. PMID: 30077125, DOI: 10.1016/j.ejca.2018.06.031.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsBaseline PD-L1 expressionObjective response ratePD-L1 expressionPD-L1Immune cellsGrade treatment-related adverse eventsSurvival rateCell lung cancer cohortLong-term clinical benefitTumor-infiltrating immune cellsTumor cellsPhase IPrevious systemic therapySingle-agent atezolizumabCell lung cancerExploratory subgroup analysisLung cancer cohortAtezolizumab monotherapyAdverse eventsDurable responsesMedian durationSystemic therapyAnticancer immunityPD-1
2016
Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer
Morgensztern D, Herbst RS. Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer. Clinical Cancer Research 2016, 22: 3713-3717. PMID: 27252413, DOI: 10.1158/1078-0432.ccr-15-2998.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungClinical Trials, Phase I as TopicHumansLung NeoplasmsNivolumabPrognosisProgrammed Cell Death 1 ReceptorRandomized Controlled Trials as TopicTreatment OutcomeConceptsCheckpoint inhibitorsClinical trialsAdvanced stage non-small lung cancerDeath-1 checkpoint inhibitorsLarge randomized clinical trialsNon-small lung cancerSecond-line docetaxelSurvivors 3 yearsBest supportive careSubset of patientsRandomized clinical trialsOverall survivalSupportive careCombination therapyLung cancerModest benefitPatientsPhase IImmunotherapyReliable predictorTherapyInhibitorsTrialsTreatmentNivolumab
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 exposure
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
First-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
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
Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer
Herbst RS, Oh Y, Wagle A, Lahn M. Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer. Clinical Cancer Research 2007, 13: 4641s-4646s. PMID: 17671157, DOI: 10.1158/1078-0432.ccr-07-0538.Peer-Reviewed Original ResearchConceptsSerine/threonine kinase inhibitorLung cancerOral serine/threonine kinase inhibitorProtein kinase CFavorable safety profileCurrent phase IKinase CTumor cell apoptosisAkt pathwayClinical findingsSafety profilePKC inhibitorTumor-induced angiogenesisPreclinical experienceCell apoptosisEnzastaurinKinase inhibitorsPhase ICancerThe changing face of phase I protocols: A closer look at study requirements
Craft B, Kurzrock R, Herbst R, Culotta K, Stewart C, Dorsey V, Lippman S, Gingher D, Bekele N, Karp D. The changing face of phase I protocols: A closer look at study requirements. Journal Of Clinical Oncology 2007, 25: 3061-3061. DOI: 10.1200/jco.2007.25.18_suppl.3061.Peer-Reviewed Original ResearchClinical Translational Research CenterPhase II trialPhase I clinical trialPhase I trialII trialClinical trialsPhase II trialMedical oncologyTranslational Research CenterCancer clinical trialsCurrent phase ILate-phase studiesPhase I programSame time periodTherapeutic requirementsECG monitoringTrialsSignificant financial relationshipElectrocardiographyStudy requirementsOncologyStudy complexityI programMore PKPhase I participants’ views of quality of life and trial participation burdens
Cohen MZ, Slomka J, Pentz RD, Flamm AL, Gold D, Herbst RS, Abbruzzese JL. Phase I participants’ views of quality of life and trial participation burdens. Supportive Care In Cancer 2007, 15: 885-890. PMID: 17252219, DOI: 10.1007/s00520-007-0216-0.Peer-Reviewed Original ResearchConceptsTrial participationCurrent QoLPrevious cancer treatmentPhase I trialPhase I cancer trialsI cancer trialsSymptoms of diseaseStudy drugI trialCancer trialsPhysical complicationsTrial participantsSide effectsQoLCancer treatmentPhase ITrialsPotential participantsBurdenPerception of qualityProcedural burdenRespondent burdenParticipantsTreatmentBaseline ability
2004
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
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 ResearchPemetrexed in advanced NSCLC: a review of the clinical data.
Zinner RG, Fossella FV, Herbst RS. Pemetrexed in advanced NSCLC: a review of the clinical data. Oncology 2004, 18: 54-62. PMID: 15339061.Peer-Reviewed Original ResearchConceptsAdvanced NSCLCConcurrent chest radiationPhase II studySecond-line therapyPhase III trialsCell lung cancerFavorable toxicity profileTreatment of mesotheliomaChest radiationII studyIII trialsSystemic dosesThoracic malignanciesFrontline settingLung cancerClinical dataToxicity profilePlatinum agentsSide effectsUS FoodDrug AdministrationPhase IPemetrexedNSCLCNovel mechanismOblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer
Herbst RS, Frankel SR. Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer. Clinical Cancer Research 2004, 10: 4245s-4248s. PMID: 15217967, DOI: 10.1158/1078-0432.ccr-040018.Peer-Reviewed Original ResearchConceptsOblimersen sodiumLung cancerBcl-2 mRNASmall cell lung cancer patientsNon-small cell lung cancerBcl-2 protein translationFirst-line salvage therapyCell lung cancer patientsPhase IPrior chemotherapy regimenCombination of docetaxelBcl-2 antisense therapyCell lung cancerTraditional cytotoxic chemotherapyLung cancer patientsChemotherapy regimenSalvage therapyCytotoxic chemotherapyAntitumor responseCancer patientsHuman bcl-2 mRNAPreclinical studiesResponse durationResponse rateAnticancer treatmentPemetrexed in the Treatment of Advanced Non–Small-Cell Lung Cancer: A Review of the Clinical Data
Zinner RG, Herbst RS. Pemetrexed in the Treatment of Advanced Non–Small-Cell Lung Cancer: A Review of the Clinical Data. Clinical Lung Cancer 2004, 5: s67-s74. PMID: 15117428, DOI: 10.3816/clc.2004.s.006.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSecond-line activityPhase III trialsIII trialsLung cancerAdvanced non-small cell lung cancerPhase II studyFirst-line therapyCell lung cancerFavorable toxicity profileChest radiationII studyThoracic malignanciesClinical dataSignificant efficacyToxicity profileSide effectsUseful agentFDA approvalPemetrexedPhase ICisplatinTrialsFurther studiesMesothelioma
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
2001
A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer
Kim E, Lu C, Khuri F, Tonda M, Glisson B, Liu D, Jung M, Hong W, Herbst R. A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. Lung Cancer 2001, 34: 427-432. PMID: 11714540, DOI: 10.1016/s0169-5002(01)00278-1.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPhase II studyPlatinum-based chemotherapyCell lung cancerII studyLung cancerStage IV non-small cell lung cancerAdvanced non-small cell lung cancerGrade 3 nonhematological toxicitiesMedian Karnofsky performance statusPrior platinum-based chemotherapyPhase ICisplatin-based regimensPrior chemotherapy regimensGrade 4 toxicityKarnofsky performance statusPopulation of patientsDose-related toxicityNonhematological toxicitiesStable diseaseChemotherapy regimensRenal insufficiencyStage IIIBMedian survivalPerformance statusPharmacodynamic studies of the specific oral EGFR tyrosine kinase inhibitor (EGFR-TKI) zd1839 (‘Iressa’) in skin from cancer patients participating in phase I trials: histopathological and molecular consequences of receptor inhibition
Albanell J, Rojo F, Averbuch S, Feyereislova A, Herbst R, LoRusso P, Rischin D, Gee J, Nicholson R, Baselga J. Pharmacodynamic studies of the specific oral EGFR tyrosine kinase inhibitor (EGFR-TKI) zd1839 (‘Iressa’) in skin from cancer patients participating in phase I trials: histopathological and molecular consequences of receptor inhibition. European Journal Of Cancer 2001, 37: s159. DOI: 10.1016/s0959-8049(01)81071-6.Peer-Reviewed Original Research
2000
A phase I study of carboplatin (Car) and docetaxel (Doc) followed by weekly Car/Doc with concurrent radiotherapy (CT/RT) in patients (pts) with stage III non-small cell lung cancer (NSCLC)
Skarin A, Lynch C, Lucca J, Boral A, Lynch T, Herbst R, Berman S, Choi N, Mathisen D, Sugarbaker D. A phase I study of carboplatin (Car) and docetaxel (Doc) followed by weekly Car/Doc with concurrent radiotherapy (CT/RT) in patients (pts) with stage III non-small cell lung cancer (NSCLC). Lung Cancer 2000, 29: 112. DOI: 10.1016/s0169-5002(00)80372-4.Peer-Reviewed Original Research