2021
457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination 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, 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. 457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination therapy for non–small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2021, 9: a485-a485. DOI: 10.1136/jitc-2021-sitc2021.457.Peer-Reviewed Original ResearchTreatment-related adverse eventsNon-small cell lung cancerAdvanced non-small cell lung cancerCombination therapyInterim analysisBiomarker subgroupsMost treatment-related adverse eventsT-cell-inflamed gene expression profileHigh subgroupBiomarker-defined subgroupsPrimary end pointPhase 2 studyPhase 2 trialFirst-line pembrolizumabCell lung cancerFirst interim analysisSubsidiary of MerckInstitutional review boardRECIST v1.1Data cutoffAdverse eventsDohme Corp.Lung cancerMature dataStudy protocol
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 monotherapyUse of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim D, Han J, Molina JR, Kim J, Arvis C, Ahn M, Majem M, Fidler MJ, Surmont V, de Castro G, Garrido M, Shentu Y, Emancipator K, Samkari A, Jensen EH, Lubiniecki GM, Garon EB. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Annals Of Oncology 2019, 30: 281-289. PMID: 30657853, PMCID: PMC6931268, DOI: 10.1093/annonc/mdy545.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiopsyCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDocetaxelFemaleFollow-Up StudiesHumansInternational AgenciesLung NeoplasmsMaleMiddle AgedParaffin EmbeddingPrognosisSpecimen HandlingSurvival RateYoung AdultConceptsTumor proportion scoreOS hazard ratioPD-L1 expressionProgression-free survivalPFS hazard ratioHazard ratioOverall survivalTumor samplesPD-L1PD-L1 tumor proportion scorePrespecified exploratory analysisPrimary end pointSubset of patientsCell lung cancerDeath 1 proteinArchival samplesDocetaxel 75KEYNOTE-010Pembrolizumab dosesRECIST v1.1Advanced NSCLCLung cancerProportion scorePatientsPrimary analysis
2017
Factors associated with better overall survival (OS) in patients with previously treated, PD-L1–expressing, advanced NSCLC: Multivariate analysis of KEYNOTE-010.
Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J, Molina J, Kim J, Dubos Arvis C, Ahn M, Majem M, Fidler M, Castro G, Garrido M, Ellison M, Samkari A, Lubiniecki G, Garon E. Factors associated with better overall survival (OS) in patients with previously treated, PD-L1–expressing, advanced NSCLC: Multivariate analysis of KEYNOTE-010. Journal Of Clinical Oncology 2017, 35: 9090-9090. DOI: 10.1200/jco.2017.35.15_suppl.9090.Peer-Reviewed Original ResearchOverall survivalKEYNOTE-010Advanced NSCLCPD-L1Multivariate analysisPembrolizumab armBetter OSHazard ratioCox proportional hazards regression modelNormal baseline lactate dehydrogenaseProportional hazards regression modelsBaseline lactate dehydrogenasePD-L1 TPSPositive advanced NSCLCSuperior overall survivalBetter overall survivalIndependent central reviewHazards regression modelsLactate dehydrogenaseEGFR mutation statusNonsquamous histologyRECIST v1.1Smoking statusTumor characteristicsCentral review
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 surgeryA study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors.
Herbst R, Gordon M, Fine G, Sosman J, Soria J, Hamid O, Powderly J, Burris H, Mokatrin A, Kowanetz M, Leabman M, Anderson M, Chen D, Hodi F. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. Journal Of Clinical Oncology 2013, 31: 3000-3000. DOI: 10.1200/jco.2013.31.15_suppl.3000.Peer-Reviewed Original ResearchPD-L1RECIST responseSolid tumorsTumor-specific T cell immunityPD-L1 tumor statusDose-escalation cohortsTumor PD-L1PD-L1 antibodiesCancer immune evasionMetastatic solid tumorsT cell immunityPD ratePD-L1 bindingHuman monoclonal antibodyVariety of tumorsMultiple tumor typesProlonged SDsRECIST v1.1Expansion cohortDurable responsesMedian durationRadiographic progressionPD-1Negative tumorsTumor shrinkage