2020
Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial
Chau I, Penel N, Soriano AO, Arkenau HT, Cultrera J, Santana-Davila R, Calvo E, Le Tourneau C, Zender L, Bendell JC, Mi G, Gao L, McNeely SC, Oliveira JM, Ferry D, Herbst RS, Fuchs CS. Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial. Cancers 2020, 12: 2985. PMID: 33076423, PMCID: PMC7602637, DOI: 10.3390/cancers12102985.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalOverall survivalPD-L1GEJ cancerGrade 3 treatment-related adverse eventsTreatment-related adverse eventsAlanine/aspartate aminotransferaseDurable clinical activityFirst-line patientsPrior systemic chemotherapyAntitumor activityDuration of responseSpectrum of patientsStudy design limitationsCheckpoint inhibitorsMetastatic settingPrimary endpointSecondary endpointsSystemic chemotherapyTreatment-naïveAdvanced gastricAdverse eventsAdvanced cancerPositive tumors
2019
SO-002 Safety and antitumor activity from the phase Ib study of ramucirumab plus pembrolizumab in treatment-naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (JVDF)
Chau I, Bendell J, Soriano A, Arkenau H, Cultrera J, Santana-Davila R, Calvo E, Le Tourneau C, Zender L, Mi G, Schelman W, Ferry D, Herbst R, Fuchs C. SO-002 Safety and antitumor activity from the phase Ib study of ramucirumab plus pembrolizumab in treatment-naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (JVDF). Annals Of Oncology 2019, 30: iv122. DOI: 10.1093/annonc/mdz157.001.Peer-Reviewed Original Research
2018
Safety and antitumor activity of ramucirumab plus pembrolizumab in treatment naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Preliminary results from a multi-disease phase I study (JVDF).
Chau I, Penel N, Arkenau H, Santana-Davila R, Calvo E, Soriano A, Mi G, Jin J, Ferry D, Herbst R, Fuchs C. Safety and antitumor activity of ramucirumab plus pembrolizumab in treatment naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Preliminary results from a multi-disease phase I study (JVDF). Journal Of Clinical Oncology 2018, 36: 101-101. DOI: 10.1200/jco.2018.36.4_suppl.101.Peer-Reviewed Original ResearchTreatment-related adverse eventsGEJ adenocarcinomaMedian durationPD-L1Study treatmentPreliminary efficacyGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsDay 1Grade treatment-related adverse eventsPhase 1a/b trialMedian progression-free survivalCell death 1 proteinAntitumor activityDisease control rateECOG PS 0Median overall survivalMedian treatment durationPD-L1 statusProgression-free survivalGrowth factor receptor 2Gastroesophageal junction adenocarcinomaDeath 1 proteinBaseline tumor tissueEndothelial growth factor receptor 2
2017
Immuno-thermal ablations – boosting the anticancer immune response
Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations – boosting the anticancer immune response. Journal For ImmunoTherapy Of Cancer 2017, 5: 78. PMID: 29037259, PMCID: PMC5644150, DOI: 10.1186/s40425-017-0284-8.Peer-Reviewed Original ResearchConceptsImmune responseImmune effectsRobust antitumor responseAnticancer immune responseImmune modulating drugsUse of immunomodulationSystemic antitumor activityCheckpoint blockadeAntitumor responseAblative therapyCombination therapyRadiofrequency ablationAblative techniquesModulating drugsAnimal modelsAntitumor activityThermal ablationTherapeutic appealImmunomodulationTherapyAblationResponseMonotherapyImmunomodulatorsCryoablation
2016
Immune checkpoint therapy for non-small-cell lung cancer: an update
Xia B, Herbst RS. Immune checkpoint therapy for non-small-cell lung cancer: an update. Immunotherapy 2016, 8: 279-298. PMID: 26860624, DOI: 10.2217/imt.15.123.Peer-Reviewed Original ResearchConceptsCell lung cancerImmune checkpointsLung cancerCo-inhibitory immune checkpointsRole of immunotherapyImmune checkpoint therapyImmune checkpoint pathwaysSynergistic antitumor activityCheckpoint inhibitorsInhibitory checkpointsCheckpoint therapyL1 antibodyImmune cellsNovel therapiesImmune activityAntagonist antibodyTumor growthTumor microenvironmentTumor cellsTherapyAntitumor activityAntibodiesCancerImmunotherapyCells
2010
Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice
Jacoby JJ, Erez B, Korshunova MV, Williams RR, Furutani K, Takahashi O, Kirkpatrick L, Lippman SM, Powis G, O'Reilly MS, Herbst RS. Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice. Journal Of Thoracic Oncology 2010, 5: 940-949. PMID: 20512076, PMCID: PMC3782111, DOI: 10.1097/jto.0b013e3181dc211f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsApoptosisBlotting, WesternCarcinoma, Non-Small-Cell LungDisease ProgressionHumansHypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesLung NeoplasmsLymphatic MetastasisMaleMiceMice, NudeMustard CompoundsPhenylpropionatesSmall Cell Lung CarcinomaSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsLung tumor volumePX-478Tumor volumeLung cancerNSCLC modelsLung adenocarcinomaNon-small cell lung cancer xenograftsSmall cell lung cancer modelCell lung cancer xenograftsHuman small cell lung cancerSmall cell lung cancerCell lung cancer modelsPhase I clinical trialPX-478 treatmentAntitumor activityDaily oral treatmentMedian survival durationVehicle-treated groupCell lung cancerLung cancer xenograftsLung cancer patientsLung adenocarcinoma cell modelsLung cancer cell linesLung cancer modelOrthotopic mouse modelPhase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer
Herbst RS, Eckhardt SG, Kurzrock R, Ebbinghaus S, O'Dwyer PJ, Gordon MS, Novotny W, Goldwasser MA, Tohnya TM, Lum BL, Ashkenazi A, Jubb AM, Mendelson DS. Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer. Journal Of Clinical Oncology 2010, 28: 2839-2846. PMID: 20458040, DOI: 10.1200/jco.2009.25.1991.Peer-Reviewed Original ResearchConceptsRecombinant human Apo2L/TRAILRhApo2L/TRAILDose-escalation studyAdverse eventsAdvanced cancerLiver metastasesDose escalationLiver functionApo2L/TRAILI dose-escalation studyDurable partial responseRapid tumor necrosisAntitumor activityCommon adverse eventsLiver enzyme elevationMetastatic liver diseaseSerious adverse eventsAbnormal liver functionNormal liver functionMultiple intravenous dosesNecrosis factor-related apoptosis-inducing ligandPreclinical antitumor efficacyTumor necrosis factor-related apoptosis-inducing ligandFactor-related apoptosis-inducing ligandHuman clinical trialsMolecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor
Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor. Molecular Cancer Therapeutics 2010, 9: 706-717. PMID: 20197390, PMCID: PMC2837366, DOI: 10.1158/1535-7163.mct-09-0985.Peer-Reviewed Original ResearchMeSH Keywords3-Phosphoinositide-Dependent Protein KinasesAnimalsAntineoplastic AgentsFemaleHumansMiceMice, Inbred C57BLMice, NudeModels, BiologicalOncogene Protein v-aktProtein BindingProtein Interaction Domains and MotifsProtein Kinase InhibitorsProtein Serine-Threonine KinasesSulfonamidesThiadiazolesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsAntitumor activityTumor xenograftsNon-small cell lung cancerMolecular pharmacologyCell lung cancerAdditive antitumor activityHuman tumor xenograftsPHT-427K-ras mutant tumorsVivo antitumor activityLung cancerSensitive tumorsPIK3CA mutationsBreast cancerImmunodeficient miceBlood chemistryMutant tumorsCombination studiesResistant cellsMinimal toxicityWeight lossTumorsCancerCancer cellsAkt inhibition
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 profileAntitumor activity of cediranib in patients with metastatic or recurrent head and neck cancer (HNC) or recurrent non-small cell lung cancer (NSCLC): An open-label exploratory study
Saura C, Baselga J, Herbst R, del Campo J, Marotti M, Tessier J, Collins B, Heymach J. Antitumor activity of cediranib in patients with metastatic or recurrent head and neck cancer (HNC) or recurrent non-small cell lung cancer (NSCLC): An open-label exploratory study. Journal Of Clinical Oncology 2009, 27: 6023-6023. DOI: 10.1200/jco.2009.27.15_suppl.6023.Peer-Reviewed Original ResearchNon-small cell lung cancerFDG-PETTumor sizeCediranib monotherapyDay 22Manageable adverse event profileOpen-label exploratory studyEffects of cediranibRECIST response rateAntitumor activityCommon adverse eventsPre-treated patientsAdverse event profileCell lung cancerTumor metabolic activityPost-baseline measurementEvidence of responseEvaluable patientsRecurrent HNCUnacceptable toxicityAdverse eventsRecurrent headFDG uptakeClinical benefitEvent profile
2006
Safety and antitumor activity of AMG 706 in patients (pts) with thyroid cancer (TC): A subset analysis from a phase 1 dose-finding study
Boughton D, Rosen L, Van Vugt A, Kurzrock R, Eschenberg M, Wiezorek J, Ingram M, Wang D, Stepan D, Herbst R. Safety and antitumor activity of AMG 706 in patients (pts) with thyroid cancer (TC): A subset analysis from a phase 1 dose-finding study. Journal Of Clinical Oncology 2006, 24: 3030-3030. DOI: 10.1200/jco.2006.24.18_suppl.3030.Peer-Reviewed Original ResearchAMG 706Partial responseThyroid cancerStable diseaseAntitumor activityPhase 1 dose-finding studyTreatment-related adverse eventsPhase 2 studyRefractory solid tumorsStage IV diseasePhase 1 studySmall-molecule multi-kinase inhibitorAdvanced thyroid cancerMedullary thyroid cancerDose-finding studyDirect antitumor activityMulti-kinase inhibitorECOG 1Baseline demographicsObjective responseProgressive diseaseAdverse eventsMedian ageMedian timeConfirmation of responseSafety and pharmacokinetics (PK) of AMG 706, panitumumab, and carboplatin/paclitaxel (CP) for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Blumenschein G, Sandler A, O’Rourke T, Eschenberg M, Sun Y, Gladish G, Salgia R, Alden C, Herbst R, Reckamp K. Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and carboplatin/paclitaxel (CP) for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2006, 24: 7119-7119. DOI: 10.1200/jco.2006.24.18_suppl.7119.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerCarboplatin/paclitaxelAMG 706Epidermal growth factor receptorDose cohortsStage IIIB/IV non-small cell lung cancerTreatment-related adverse eventsPhase 1b studyAntitumor activityObjective response rateCell lung cancerTreatment of patientsDirect antitumor activityMulti-kinase inhibitorHuman monoclonal antibodyPreliminary dataCNS metastasisGrowth factor receptorPrior chemotherapyQD cohortAdverse eventsMedian ageECOG scoreAcceptable safety
2004
Overview of the Current Status of Human Epidermal Growth Factor Receptor Inhibitors in Lung Cancer
Herbst RS, Sandler AB. Overview of the Current Status of Human Epidermal Growth Factor Receptor Inhibitors in Lung Cancer. Clinical Lung Cancer 2004, 6: s7-s19. PMID: 15638959, DOI: 10.3816/clc.2004.s.009.Peer-Reviewed Original ResearchConceptsThird-line treatmentLung cancerMetastatic NSCLCHER1/EGFR tyrosine kinase inhibitorsPhase III placebo-controlled trialHER1/EGFR inhibitorsEpidermal growth factor receptor inhibitorsEGFR tyrosine kinase inhibitorsGrowth factor receptor inhibitorsHuman epidermal growth factor receptorAntitumor activityPlacebo-controlled trialMetastatic colorectal carcinomaPhase III trialsCell lung cancerStandard of careTyrosine kinase inhibitorsEGFR tyrosine kinase domainEpidermal growth factor receptorHuman epidermal growth factor receptor inhibitorsPhase II dataGrowth factor receptorRefractory NSCLCChemotherapy combinationsIII trials
2003
Mode of action of docetaxel – a basis for combination with novel anticancer agents
Herbst RS, Khuri FR. Mode of action of docetaxel – a basis for combination with novel anticancer agents. Cancer Treatment Reviews 2003, 29: 407-415. PMID: 12972359, DOI: 10.1016/s0305-7372(03)00097-5.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsApoptosisDocetaxelDrug Resistance, NeoplasmDrug SynergismErbB ReceptorsFemaleFollow-Up StudiesHumansMaleNeoplasmsNeovascularization, PathologicPaclitaxelPharmacogeneticsSurvival AnalysisTaxoidsTreatment OutcomeConceptsPatient populationOptimal treatment strategySpecific patient populationsCertain chemotherapeutic drugsAnticancer agentsOptimal therapySpecific therapyTreatment strategiesNovel agentsClinical investigationNew anticancer agentsNovel anticancer agentsCancer growthDifferent tumorsStimulation pathwayChemotherapeutic drugsInhibitor of mitosisAntitumor activityTumorigenic mechanismsMode of actionAgent combinationsDocetaxelTherapyAgentsDifferent aberrationsErlotinib (Tarceva): An update on the clinical trial program
Herbst RS. Erlotinib (Tarceva): An update on the clinical trial program. Seminars In Oncology 2003, 30: 34-46. PMID: 12840799, DOI: 10.1016/s0093-7754(03)70013-x.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdvanced non-small cell lung cancerPhase II monotherapy trialsNeck squamous cell cancerUse of erlotinibAntitumor activitySingle-agent chemotherapyPhase III trialsClinical trial programSquamous cell cancerSimilar patient populationsSubstantial antitumor activityHuman tumor xenograftsMonotherapy trialsEpidermal growth factor receptor tyrosine kinaseIII trialsCell cancerPatient populationPancreatic cancerOvarian cancerPreclinical studiesGrowth factor receptor tyrosine kinaseTumor xenografts
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 XVIIIE-SelectinEndostatinsEndothelial Growth FactorsFemaleFibroblast 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 ISelective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial.
Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, Rojo F, Hong WK, Swaisland H, Averbuch SD, Ochs J, LoRusso PM. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. Journal Of Clinical Oncology 2002, 20: 3815-25. PMID: 12228201, DOI: 10.1200/jco.2002.03.038.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFemaleGastrointestinal DiseasesGefitinibHead and Neck NeoplasmsHumansLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsProtein-Tyrosine KinasesQuinazolinesSkin DiseasesConceptsDose-limiting toxicityPharmacokinetic analysisEpidermal growth factor receptor tyrosine kinase inhibitor ZD1839Epidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsGrade 1/2 adverse eventsTyrosine kinase inhibitor ZD1839Primary dose-limiting toxicityReceptor tyrosine kinase inhibitorsPrior cancer therapyAntitumor activityDaily oral dosingPhase I trialCell lung cancerTyrosine kinase inhibitorsSolid tumor typesVariability of exposureStable diseaseAdverse eventsPartial responseUndue toxicityI trialTolerability trialCell lungFollicular rashThe role of the epidermal growth factor receptor in the treatment of colorectal carcinoma
Waxman ES, Herbst RS. The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma. Seminars In Oncology Nursing 2002, 18: 20-29. PMID: 12053861, DOI: 10.1053/sonu.2002.33072.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorColorectal carcinomaGrowth factor receptorClinical experienceAnti-EGFR monoclonal antibodiesTraditional cytotoxic approachesFactor receptorExtensive clinical testingTyrosine kinase inhibitorsEarly clinical experienceVariety of tumorsSignificant antitumor activityBiological agentsTreatment of cancerCytotoxic approachesEGFR resultsClinical testingNursing practiceCarcinomaMonoclonal antibodiesEGFR pathwayKinase inhibitorsAntitumor activityVariety of mechanismsReceptors