2020
Immune profiling and clinical outcomes in patients treated with ramucirumab and pembrolizumab in phase I study JVDF.
Herbst R, Arkenau H, Calvo E, Bendell J, Penel N, Fuchs C, McNeely S, Rasmussen E, Wang H, Oliveira J, Ferry D, Chau I. Immune profiling and clinical outcomes in patients treated with ramucirumab and pembrolizumab in phase I study JVDF. Journal Of Clinical Oncology 2020, 38: 3089-3089. DOI: 10.1200/jco.2020.38.15_suppl.3089.Peer-Reviewed Original ResearchNon-small cell lung cancerPD-L1 protein expressionObjective response rateBiliary tract cancerProgression-free survivalClinical outcomesOverall survivalUrothelial carcinomaProtein expressionDako PD-L1 IHC 22C3 pharmDxAdvanced non-small cell lung cancerDay 1Phase 1a/b trialImmune checkpoint-related genesPD-L1 IHC 22C3 pharmDxPD-L1 negative tumorsPD-L1 positive tumorsMyeloid-derived suppressor cellsPD-L1 gene expressionTumor microenvironmentPanCancer Immune Profiling PanelImmune-related gene signatureImmune-related gene expressionBaseline tumor samplesGastroesophageal junction adenocarcinoma
2019
Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial
Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. The Lancet Oncology 2019, 20: 1109-1123. PMID: 31301962, DOI: 10.1016/s1470-2045(19)30458-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Transitional CellDose-Response Relationship, DrugEsophageal NeoplasmsFemaleHumansLung NeoplasmsMaleMiddle AgedStomach NeoplasmsConceptsGastro-oesophageal junction adenocarcinomaTreatment-related adverse eventsCell lung cancerPhase 1a/b trialSerious adverse eventsDose-limiting toxicityAdverse eventsJunction adenocarcinomaUrothelial carcinomaLung cancerDay 1VEGF receptor 2Abdominal painPrevious therapyAdvanced gastricEastern Cooperative Oncology Group performance statusAntigen-specific T-cell migrationMore treatment-related adverse eventsTreatment-related serious adverse eventsAdditional dose-limiting toxicitiesCell lung cancer cohortGrade 3 abdominal painSingle-agent checkpoint inhibitorsB trialAntitumour activity
2018
Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open‐Label, Phase I Trial (JVDF)
Arkenau H, Martin‐Liberal J, Calvo E, Penel N, Krebs MG, Herbst RS, Walgren RA, Widau RC, Mi G, Jin J, Ferry D, Chau I. Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open‐Label, Phase I Trial (JVDF). The Oncologist 2018, 23: 1407-e136. PMID: 29853658, PMCID: PMC6292555, DOI: 10.1634/theoncologist.2018-0044.Peer-Reviewed Original ResearchConceptsMetastatic biliary tract cancerTreatment-related adverse eventsBiliary tract cancerObjective response rateProgression-free survivalOverall survivalTract cancerCommon grade 3 treatment-related adverse eventsGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsDay 1Response rateAdvanced biliary tract cancerMedian progression-free survivalBiomarker-unselected patientsEfficacy of ramucirumabInfrequent grade 3Limited clinical activityPD-1 antagonistsTreatment-related deathsUnexpected safety findingsVEGFR-2 antagonistGrowth factor receptor 2Phase I trialExtrahepatic bile ductSafety 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
Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease phase I study.
Chau I, Bendell J, Calvo E, Santana-Davila R, Arkenau H, Mi G, Jin J, Rege J, Ferry D, Herbst R, Fuchs C. Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease phase I study. Journal Of Clinical Oncology 2017, 35: 4046-4046. DOI: 10.1200/jco.2017.35.15_suppl.4046.Peer-Reviewed Original ResearchTreatment-related AEsDisease control rateECOG PSMedian durationMedian agePD-L1GEJ adenocarcinomaDay 1Phase 1a/b trialECOG PS 0Experienced grade 3Treatment-related deathsNew safety signalsPD-L1 statusOverall survival rateGastroesophageal junction adenocarcinomaPreliminary efficacy dataMeasurable diseaseMedian PFSAdvanced diseaseTreatment-naïveAdvanced gastricPS 0Junction adenocarcinomaCohort AA multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma.
Petrylak D, Arkenau H, Perez-Gracia J, Krebs M, Santana-Davila R, Yang J, Rege J, Mi G, Ferry D, Herbst R. A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma. Journal Of Clinical Oncology 2017, 35: 349-349. DOI: 10.1200/jco.2017.35.6_suppl.349.Peer-Reviewed Original ResearchTreatment-related AEsECOG PS 0Median durationPS 0PD-L1Urothelial carcinomaDay 1Phase 1a/b trialPlatinum-based systemic therapyTreatment-related grade 4Advanced urothelial carcinomaElevated alanine aminotransferaseNew safety signalsElevated aspartate aminotransferaseBaseline tumor tissuePreliminary efficacy dataTransitional cell carcinomaEligible ptsMeasurable diseaseMedian PFSStable diseasePartial responseProgressive diseaseSystemic therapyMedian age
2011
An Open-Label, Multicenter, Three-Stage, Phase II Study of S-1 in Combination with Cisplatin as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer
Sandler A, Graham C, Baggstrom M, Herbst R, Zergebel C, Saito K, Jones D. An Open-Label, Multicenter, Three-Stage, Phase II Study of S-1 in Combination with Cisplatin as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer. Journal Of Thoracic Oncology 2011, 6: 1400-1406. PMID: 21673602, DOI: 10.1097/jto.0b013e31820d7805.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCisplatinDrug CombinationsFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOxonic AcidSurvival RateTegafurTreatment OutcomeConceptsNon-small cell lung cancerCell lung cancerLung cancerUnresectable non-small cell lung cancerAdvanced non-small cell lung cancerDay 1Response rateBest overall response rateMedian progression-free survivalCisplatin-based doubletsProtocol-specified criteriaDisease control rateObjective response ratePrimary end pointPhase II studyProgression-free survivalDeep vein thrombosisOverall response rateCisplatin regimenGastrointestinal toxicityOpen labelOral agentsAdverse eventsII studyLine therapyA 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
2009
Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor
Jimeno A, Hong D, Hecker S, Clement R, Kurzrock R, Pestano L, Hiscox A, Leos R, Kirkpatrick D, Eckhardt S, Herbst R. Phase I trial of PX-866, a novel phosphoinositide-3-kinase (PI-3K) inhibitor. Journal Of Clinical Oncology 2009, 27: 3542-3542. DOI: 10.1200/jco.2009.27.15_suppl.3542.Peer-Reviewed Original ResearchPX-866Stable diseaseClinical trialsDay 1Drug-related severe adverse eventsMild side effect profilePhase 1 clinical trialStabilization of diseaseSevere adverse eventsDose-limiting toxicityPhase I trialSide effect profileAdvanced metastatic cancerP-mTOR levelsDose-dependent inhibitionLower drug dosesPhosphoinositide-3 kinase inhibitorPD endpointsExpansion cohortLast doseAbdominal discomfortAdverse eventsI trialEffect profileLoss of PTENS0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study
Gandara D, Kim E, Herbst R, Moon J, Redman M, Dakhil S, Hirsch F, Mack P, Franklin W, Kelly K. S0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study. Journal Of Clinical Oncology 2009, 27: 8015-8015. DOI: 10.1200/jco.2009.27.15_suppl.8015.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerProgression-free survivalOverall survivalEGFR FISHStable diseasePartial responseNon-squamous cell non-small cell lung cancerDay 1Median age 64 yearsTreatment-related deathsDisease control ratePhase II studyPhase III trialsPlatinum-based chemotherapyAge 64 yearsCell lung cancerEfficacy of carboplatinActive regimenAUC 6Bevacizumab maintenanceEligible ptsMedian followBrain metastasesEfficacy outcomes
2006
Apo2L/TRAIL pharmacokinetics in a phase 1a trial in advanced cancer and lymphoma
Ling J, Herbst R, Mendelson D, Eckhardt S, O’Dwyer P, Ebbinghaus S, Osborne R, Cheu M, Lieberman G, Lum B. Apo2L/TRAIL pharmacokinetics in a phase 1a trial in advanced cancer and lymphoma. Journal Of Clinical Oncology 2006, 24: 3047-3047. DOI: 10.1200/jco.2006.24.18_suppl.3047.Peer-Reviewed Original ResearchApo2L/TRAILCohort 1PK dataSerum concentrationsCohort 2Preclinical modelsRecombinant human Apo2L/TRAILPhase 1a studyPhase 1a trialMild liver dysfunctionNon-compartmental analysisTumor xenograft modelSensitive ELISA assayLiver dysfunctionLiver metastasesPK assessmentAdvanced cancerHepatic metastasesIV infusionNonclinical modelsHematologic cancersXenograft modelClinical developmentDay 1Dose levels
2004
A phase I surrogate endpoint study of SU6668 in patients with solid tumors
Xiong HQ, Herbst R, Faria SC, Scholz C, Davis D, Jackson EF, Madden T, McConkey D, Hicks M, Hess K, Charnsangavej C, Abbruzzese JL. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Investigational New Drugs 2004, 22: 459-466. PMID: 15292716, DOI: 10.1023/b:drug.0000036688.96453.8d.Peer-Reviewed Original ResearchConceptsCore needle biopsyBiologic effectsNeedle biopsyDay 1Solid tumorsMean apparent oral clearanceContrast-enhanced magnetic resonance imagingApparent oral clearanceDynamic contrast-enhanced magnetic resonance imagingCorrelative studiesHigh-performance liquid chromatography assayMagnetic resonance imagingDCE-MRI resultsEligible patientsOral clearanceLiquid chromatography assayEndpoint studiesAntiangiogenic agentsFunctional CTBlood flowTumor specimensPatientsTissue biopsiesDay 22PK studies
2003
A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Herbst RS, Hammond LA, Carbone DP, Tran HT, Holroyd KJ, Desai A, Williams JI, Bekele BN, Hait H, Allgood V, Solomon S, Schiller JH. A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clinical Cancer Research 2003, 9: 4108-15. PMID: 14519633.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiogenesis InhibitorsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCholestanolsDisease-Free SurvivalFemaleHumansInfusions, IntravenousLactatesLung NeoplasmsMaleMiddle AgedNeoplasm StagingPaclitaxelPatient SelectionPleural EffusionSurvival AnalysisTime FactorsConceptsNon-small cell lung cancerCell lung cancerLung cancerDay 1Continuous infusionChemotherapy-naive non-small cell lung cancerAdvanced non-small cell lung cancerPhase I/IIa studyPhase I/IIa trialPhase II doseDose-limiting toxicityPartial tumor responseFive-day infusionEffective therapeutic strategyPatient survival dataEvaluable patientsStable diseaseStage IIIBStarting doseClinical responseCombination regimenCytotoxic chemotherapyIIa studyIIa trialMedian survival
2002
The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma
Herbst RS, Khuri FR, Lu C, Liu DD, Fossella FV, Glisson BS, Pisters KM, Shin DM, Papadimitrakopoulou VA, Kurie JM, Blumenschein G, Kies MS, Zinner R, Jung MS, Lu R, Lee JJ, Munden RF, Hong WK, Lee JS. The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma. Cancer 2002, 95: 340-353. PMID: 12124835, DOI: 10.1002/cncr.10629.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntimetabolites, AntineoplasticAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBiological TherapyCarcinoma, Non-Small-Cell LungCombined Modality TherapyDeoxycytidineDisease ProgressionFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedSurvival RateVinblastineVinorelbineConceptsNonsmall cell lung carcinomaYear survival rateAdvanced nonsmall cell lung carcinomaThird-line therapyPhase II trialMedian survival timeCell lung carcinomaGrade 3Survival rateSignificant myelosuppressionStable diseaseII trialLung carcinomaSurvival timeStage IV nonsmall cell lung carcinomaDay 1Day 15Formal phase II trialCurrent phase II trialDose of vinorelbineGemcitabine/vinorelbineGrade 3 granulocytopeniaMedian performance statusMinimal grade 3Prior chemotherapy regimensRandomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: Preliminary results
Komaki R, Lee J, Kaplan B, Allen P, Kelly J, Liao Z, Stevens C, Fossella F, Zinner R, Papadimitrakopoulou V, Khuri F, Glisson B, Pisters K, Kurie J, Herbst R, Milas L, Ro J, Thames H, Hong W, Cox J. Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: Preliminary results. Seminars In Radiation Oncology 2002, 12: 46-49. PMID: 11917284, DOI: 10.1053/srao.2002.31363.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerThoracic radiation therapyInoperable stage IICell lung cancerSevere esophagitisArm 2Arm 1Lung cancerDay 1Randomized phase III studyStage IIPhase III studyGy/fractionMedian survival timeLong-term efficacyOral etoposideAcute pneumonitisConcurrent chemoradiotherapyIII studyTumor characteristicsPulmonary toxicityStudy groupRadiation therapyDay 29Survival time
1999
Gemcitabine and vinorelbine combinations in the treatment of non-small cell lung cancer.
Herbst RS, Lilenbaum R. Gemcitabine and vinorelbine combinations in the treatment of non-small cell lung cancer. Seminars In Oncology 1999, 26: 67-70; discussion 71-2. PMID: 10585011.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerVinorelbine/gemcitabineCell lung cancerMedian survivalSurvival rateStable diseasePartial responseLung cancerDisease progressionDay 1Treatment of NSCLCStandard platinum-based regimensGemcitabine/vinorelbineChemotherapy-naive patientsPerformance status 0Treatment-naive patientsPhase II studyPlatinum-based regimensCombination of vinorelbineMedian survival timeOverall response rateNonplatinum agentsStatus 0Vinorelbine combination