2023
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen W, Percent I, Calderon V, Johnson M, Madroszyk-Flandin A, Garon E, He K, Planchard D, Reck M, Popat S, Herbst R, Leal T, Shazer R, Yan X, Harrigan R, Peters S, Investigators S, Abdel-Karim I, Abdelsalam M, Addeo A, Aguado C, Alexander P, Alt J, Azzi G, Balaraman R, Biesma B, Blackhall F, Bohnet S, Boleti E, Borghaei H, Bradbury P, Brighenti M, Campbell N, Campbell T, Canon J, Cappuzzo F, Costa E, Cavanna L, Cetnar J, Chella A, Chouaid C, Christoph D, Castán J, Dakhil S, de Castro Carpeño F, de Marinis F, Delmonte A, Demedts I, Demey W, Dits J, del Pilar Diz Taín M, Gómez M, Dorius T, Dumoulin D, Duruisseaux M, Eaton K, González E, Evans D, Faehling M, Farrell N, Feinstein T, Font E, Campelo M, Garon E, López M, Germonpré P, Gersten T, Cao M, Gopaluni S, Greillier L, Grossi F, Guisier F, Gurubhagavatula S, Calderón V, Hakimian D, Hall R, Hao D, Harris R, Hashemi S, He K, Hendriks L, Huang C, Ibrahim E, Jain S, Johnson M, Jones B, Jones M, Vidal Ó, Juergens R, Kaderbhai C, Kastelijn E, Keresztes R, Kio E, Kokowski K, Konduri K, Kulkarni S, Kuon J, Kurkjian C, Labbé C, Lerner R, Lim F, Madroszyk-Flandin A, Marathe O, Martincic D, McClay E, McIntyre K, Mekhail T, Misino A, Molinier O, Morabito A, Morócz É, Müller V, Nagy T, Nguyen A, Nidhiry E, Okazaki I, Ortega-Granados A, Ostoros G, Oubre D, Owen S, Pachipala K, Park D, Patel P, Percent I, Pérol M, Peters S, Piet B, Planchard D, Polychronis A, Aix S, Pons-Tostivint E, Popat S, Pulla M, Quantin X, Quéré G, Rafique N, Ramaekers R, Reck M, Reiman A, Reinmuth N, Reynolds C, Rodríguez-Abreu D, Romano G, Roque T, Salzberg M, Sanborn R, Sandiego S, Schaefer E, Schreeder M, Seetharamu N, Seneviratne L, Shah P, Shunyakov L, Slater D, Parra H, Stigt J, Stilwill J, Su J, Surmont V, Swink A, Szalai Z, Talbot T, Garcia A, Theelen W, Thompson J, Tiseo M, Uprety D, Uyeki J, van der Leest K, Van Ho A, van Putten J, Estévez S, Veatch A, Vergnenègre A, Ward P, Weise A, Weiss M, Whitehurst M, Zai S, Zalcman G, Zuniga R. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Annals Of Oncology 2023, 35: 66-76. PMID: 37866811, DOI: 10.1016/j.annonc.2023.10.004.Peer-Reviewed Original ResearchClinical benefit rateObjective response rateProgression-free survivalCell lung cancerOverall survivalNonsquamous NSCLCPrimary endpointLung cancerMedian progression-free survivalTreatment-related adverse eventsReceptor tyrosine kinase inhibitorsAdvanced nonsquamous NSCLCCheckpoint inhibitor therapyMedian overall survivalPlatinum-based chemotherapyDuration of responseImmunosuppressive tumor microenvironmentTyrosine kinase inhibitorsImmunostimulatory stateMedian DoRSecondary endpointsMost patientsAdverse eventsInhibitor therapySafety profileBiomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nature Medicine 2023, 29: 1718-1727. PMID: 37429923, DOI: 10.1038/s41591-023-02385-6.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerCell lung cancerSafety profileCombination therapyLung cancerInvestigator-assessed objective response rateRandomized phase 2 studySolid Tumors version 1.1T-cell-inflamed gene expression profileGroup IIIBiomarker-defined subgroupsFirst-line pembrolizumabPhase 2 studyProgression-free survivalResponse Evaluation CriteriaSubset of patientsHeterogenous tumor microenvironmentData cutoffOverall survivalSecondary outcomesPrimary outcomeTreatment armsTMB assessment
2022
A phase II study of talazoparib plus avelumab in patients with stage IV or recurrent nonsquamous non–small cell lung cancer bearing pathogenic STK11 genomic alterations (SWOG S1900C, LUNG-MAP sub-study, NCT04173507).
Skoulidis F, Redman M, Suga J, Al Baghdadi T, Villano J, Goldberg S, Villaruz L, Minichiello K, Gandara D, Herbst R, Kelly K. A phase II study of talazoparib plus avelumab in patients with stage IV or recurrent nonsquamous non–small cell lung cancer bearing pathogenic STK11 genomic alterations (SWOG S1900C, LUNG-MAP sub-study, NCT04173507). Journal Of Clinical Oncology 2022, 40: 9060-9060. DOI: 10.1200/jco.2022.40.16_suppl.9060.Peer-Reviewed Original ResearchObjective response ratePhase II studyCheckpoint inhibitorsII studyStage IVPrior linesGenomic alterationsSingle-arm phase II studyArm phase II studyBest objective response rateMedian progression-free survivalPARP inhibitorsAdequate organ functionCo-primary objectivesDurable disease stabilizationMost grade 3PD-L1 TPSDisease control rateImmune checkpoint inhibitorsMedian overall survivalNon-squamous NSCLCStage IV diseaseProgression-free survivalBest objective responseOptimal therapeutic approachCOAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer
Herbst RS, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez-Hernandez A, Dakhil S, Camidge DR, Winzer L, Soo-Hoo Y, Cooper ZA, Kumar R, Bothos J, Aggarwal C, Martinez-Marti A. COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2022, 40: 3383-3393. PMID: 35452273, DOI: 10.1200/jco.22.00227.Peer-Reviewed Original ResearchConceptsProgression-free survivalCell lung cancerUnresectable stage IIIConcurrent chemoradiotherapyLung cancerEastern Cooperative Oncology Group performance status 0/1Stage IIITreatment-emergent adverse eventsPerformance status 0/1Objective response ratePrimary end pointPhase II studyPhase III trialsStandard of careSignificant safety signalsPFS ratesConsolidation therapyOpen labelII studyIII trialsOverall survivalAdverse eventsDurvalumabSafety signalsMonalizumab
2021
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, Bradley JD, Stinchcombe TE, Ramalingam SS, Miao J, Minichiello K, Herbst RS, Papadimitrakopoulou VA, Kelly K, Gandara DR. Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). Journal For ImmunoTherapy Of Cancer 2021, 9: e002973. PMID: 34429332, PMCID: PMC8386207, DOI: 10.1136/jitc-2021-002973.Peer-Reviewed Original ResearchConceptsDisease progressionAnti-programmed death ligand 1 therapyStage IV squamous cell lung cancerPrior anti-PD-1 therapyResponse rateAnti-PD-1 therapyDeath ligand 1 therapyMedian progression-free survivalSquamous cell lung cancerObjective response ratePhase II studyProgression-free survivalCell lung cancerSquamous lung carcinomaDurvalumab 1500Eligible patientsImmunotherapy combinationsPrimary endpointAdverse eventsII studyOverall survivalPartial responseTRIAL REGISTRATIONLung cancerLung carcinomaA Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression
Herbst R, Jassem J, Abogunrin S, James D, McCool R, Belleli R, Giaccone G, De Marinis F. A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression. Frontiers In Oncology 2021, 11: 676732. PMID: 34307144, PMCID: PMC8300186, DOI: 10.3389/fonc.2021.676732.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalObjective response rateStage IV non-small cell lung cancerFirst-line treatmentOverall survivalCell lung cancerLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionMetastatic non-small cell lung cancerStage non-small cell lung cancerProgrammed Death Ligand 1 ExpressionTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionPD-L1 expressionPD-L1 statusAbsence of headNetwork Meta-AnalysisRisk of biasRandom-effects modelVersus ChemotherapyImmunotherapy regimenAdverse eventsHead trialsCombination regimensOutcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042
Mansfield AS, Herbst RS, de Castro G, Hui R, Peled N, Kim DW, Novello S, Satouchi M, Wu YL, Garon EB, Reck M, Robinson AG, Samkari A, Piperdi B, Ebiana V, Lin J, Mok TSK. Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042. JTO Clinical And Research Reports 2021, 2: 100205. PMID: 34590048, PMCID: PMC8474394, DOI: 10.1016/j.jtocrr.2021.100205.Peer-Reviewed Original ResearchBaseline brain metastasesPD-L1 TPSStable brain metastasesBrain metastasesKEYNOTE-001Metastatic NSCLCPembrolizumab monotherapyAdverse eventsPD-L1Treatment-related adverse eventsBrain metastasis statusEfficacy of pembrolizumabObjective response rateProgression-free survivalCell lung cancerDuration of responseKEYNOTE-010KEYNOTE-024KEYNOTE-042Data cutoffOverall survivalLung cancerMetastasis statusPresence of baselineChemotherapy
2020
Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC
Herbst RS, Arkenau HT, Bendell J, Arrowsmith E, Wermke M, Soriano A, Penel N, Santana-Davila R, Bischoff H, Chau I, Mi G, Wang H, Rasmussen E, Ferry D, Chao BH, Paz-Ares L. Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Journal Of Thoracic Oncology 2020, 16: 289-298. PMID: 33068794, DOI: 10.1016/j.jtho.2020.10.004.Peer-Reviewed Original ResearchConceptsProgression-free survivalTumor proportion scoreMedian progression-free survivalTreatment-related adverse eventsPD-L1 expressionT-cell signatureCD274 gene expressionAdverse eventsPhase 1a/b trialPD-L1 tumor proportion scoreHigh PD-L1 expressionManageable safety profileMedian overall survivalObjective response ratePD-L1 positivityFirst-line therapyOverall survival ratePD-L1 immunohistochemistryCohort EPembrolizumab treatmentPFS ratesExpansion cohortClinical responseOverall survivalEfficacy signalsRamucirumab 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 tumorsImmune 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
1589TiP KEYNOTE-495/KeyImPaCT: A randomized, biomarker-directed, phase II trial of pembrolizumab-based therapy for non–small cell lung cancer (NSCLC)
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Basso A, Ma H, Fong L, Snyder A, Yuan J, Herbst R. 1589TiP KEYNOTE-495/KeyImPaCT: A randomized, biomarker-directed, phase II trial of pembrolizumab-based therapy for non–small cell lung cancer (NSCLC). Annals Of Oncology 2019, 30: v656. DOI: 10.1093/annonc/mdz260.111.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerPhase II trialSubsidiary of MerckDohme Corp.Boehringer IngelheimRECIST v1.1II trialMerck SharpEli LillyInvestigator-assessed objective response rateRoche/GenentechEnd pointECOG PS 0Genentech/RochePembrolizumab-based therapyObjective response ratePrimary end pointSecondary end pointsProgression-free survivalROS1 gene rearrangementTumor mutation burdenCell lung cancerAbsence of EGFRYears of ageBiomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study.
Gutierrez M, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Basso A, Ma H, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study. Journal Of Clinical Oncology 2019, 37: tps9117-tps9117. DOI: 10.1200/jco.2019.37.15_suppl.tps9117.Peer-Reviewed Original ResearchCombination therapyRECIST v1.1Advanced NSCLCGene expression profilesInvestigator-assessed objective response rateNon-small cell lung cancerEnd pointT-cell-inflamed gene expression profileECOG PS 0Immune checkpoint inhibitorsObjective response ratePrimary end pointSecondary end pointsProgression-free survivalROS1 gene rearrangementCell lung cancerAbsence of EGFRInterim efficacy analysisDifferent combination therapiesCombination immunotherapyLenvatinib armLenvatinib monotherapyMeasurable diseaseCheckpoint inhibitorsPembrolizumab monotherapy
2018
Safety 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-1Ramucirumab 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 duct
2016
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Nilsson MB, Giri U, Gudikote J, Tang X, Lu W, Tran H, Fan Y, Koo A, Diao L, Tong P, Wang J, Herbst R, Johnson BE, Ryan A, Webster A, Rowe P, Wistuba II, Heymach JV. KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib. Clinical Cancer Research 2016, 22: 1940-1950. PMID: 26578684, PMCID: PMC4834253, DOI: 10.1158/1078-0432.ccr-15-1994.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationHumansHypoxia-Inducible Factor 1, alpha SubunitLung NeoplasmsP38 Mitogen-Activated Protein KinasesPiperidinesProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinazolinesSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerTyrosine kinase inhibitorsVEGFR tyrosine kinase inhibitorsNSCLC cell linesZODIAC studyClinical benefitLung cancerPlatinum-refractory non-small cell lung cancerAdvanced non-small cell lung cancerImproved progression-free survivalDifferent lung cancersObjective response rateProgression-free survivalVEGF pathway inhibitorsCell lung cancerArchival tumor samplesCell linesActivation of mTORVandetanib armOverall survivalNSCLC modelsNSCLC cellsPreclinical studiesPatientsVEGFR inhibition
2015
A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies
Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer 2015, 15: 171. PMID: 25881079, PMCID: PMC4412099, DOI: 10.1186/s12885-015-1146-8.Peer-Reviewed Original ResearchConceptsGene copy number gainCopy number gainsRET rearrangementsTumor samplesComparator armVandetanib treatmentNumber gainRandomized phase III studyPhase III clinical trialsCell lung cancer trialsObjective response ratePhase III studyLung cancer trialsRET protein expressionNSCLC subpopulationVandetanib armRadiologic evidenceIII studyNSCLC patientsObjective responseTumor shrinkageComparator drugsCancer trialsClinical trialsRetrospective analysis
2014
EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer
Heymach JV, Lockwood SJ, Herbst RS, Johnson BE, Ryan AJ. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Annals Of Oncology 2014, 25: 1941-1948. PMID: 25057173, PMCID: PMC4176452, DOI: 10.1093/annonc/mdu269.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSecond-line treatmentProgression-free survivalAdvanced non-small cell lung cancerRandomized phase III studyPhase III studyCell lung cancerMutation-positive tumorsEGFR mutationsIII studyTumor samplesClinical benefitLung cancerSecond-line non-small cell lung cancerEGFR FISH-positive tumorsEGFR mutation-positive tumorsEpidermal growth factor receptor (EGFR) gene mutationsObjective response rateRelative clinical benefitFirst-line chemotherapyObjective tumor responseProtein expressionOverall study populationGene mutationsPretreatment tumor samples
2013
Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
Spigel D, Gettinger S, Horn L, Herbst R, Gandhi L, Gordon M, Cruz C, Conkling P, Cassier P, Antonia S, Burris H, Fine G, Mokatrin A, Kowanetz M, Shen X, Chen D, Soria J. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2013, 31: 8008-8008. DOI: 10.1200/jco.2013.31.15_suppl.8008.Peer-Reviewed Original ResearchNon-small cell lung cancerObjective response ratePD-L1 tumorsPD-L1NSCLC ptsLung cancerNonsquamous non-small cell lung cancerMetastatic non-small cell lung cancerPD-L1 tumor statusAnti-cancer immune responsePD-L1 statusPD-L1 antibodiesCell lung cancerRapid tumor shrinkagePD rateArchival tumor samplesHuman lung cancerHuman monoclonal AbsNonsquamous histologyRECIST responseRECIST v1.1Prior radiotherapyDurable responsesMedian durationPrior surgeryPhase 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 trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours
Kozloff MF, Martin LP, Krzakowski M, Samuel TA, Rado TA, Arriola E, De Castro Carpeño J, Herbst RS, Tarazi J, Kim S, Rosbrook B, Tortorici M, Olszanski AJ, Cohen RB. Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. British Journal Of Cancer 2012, 107: 1277-1285. PMID: 22990652, PMCID: PMC3494447, DOI: 10.1038/bjc.2012.406.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPaclitaxel/carboplatinAdvanced non-small cell lung cancerPharmacokinetics of axitinibGemcitabine/cisplatinCell lung cancerAxitinib 5Platinum doubletsLung cancerSolid tumorsSquamous cell non-small cell lung cancerTreatment-related adverse eventsSelective second-generation inhibitorVascular endothelial growth factor receptorObjective response rateDose-limiting toxicityPhase I trialEndothelial growth factor receptorDose-finding trialDrug-drug interactionsPhase I dose-finding trialsCisplatin regimensFebrile neutropeniaGrowth factor receptorExpansion cohort