2024
Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).
Aggarwal C, Martinez-Marti A, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez A, Dakhil S, Camidge D, Pillet M, Brown M, Dowson A, Cooper Z, Kumar R, Herbst R. Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC). Journal Of Clinical Oncology 2024, 42: 8046-8046. DOI: 10.1200/jco.2024.42.16_suppl.8046.Peer-Reviewed Original ResearchUnresectable non-small cell lung cancerStage III unresectable non-small cell lung cancerProgression free survivalImmune-mediated AEConcurrent chemoradiotherapyPhase 2 studyNon-small cell lung cancerProlonged progression free survivalECOG PS 0Suppress antitumor immunityMedian follow-upCell lung cancerExpression of CD73Anti-CD73Anti-NKG2AImmunotherapy combinationsAntitumor immunityConsolidation therapyPD-L1Free survivalImmune checkpointsPS 0Open-labelProgressive diseaseDiscontinued treatment
2020
IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).
Jassem J, Herbst R, de Marinis F, Cadranel J, Csőszi T, Isla D, Chen G, Syrigos K, Cortinovis D, Hida T, Mocci S, Phan S, Enquist I, Patel H, Villalobos M, Wen X, Deng Y, Kuriki H, Spigel D, Giaccone G. IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: e21623-e21623. DOI: 10.1200/jco.2020.38.15_suppl.e21623.Peer-Reviewed Original ResearchNon-small cell lung cancerPD-L1 expressionSafety profileFirst‐line non‐small cell lung cancerCarboplatin AUC 6ECOG PS 0NCI CTCAE v4.0Chemo-naive patientsNew safety signalsPhase III studyPlatinum-based chemotherapyFavorable safety profileCell lung cancerAtezolizumab monotherapyAUC 5AUC 6Gemcitabine 1250Endocrine therapySystemic glucocorticoidsCTCAE v4.0Data cutoffIII studyPS 0PD-L1GEM 1000O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC
Herbst R, De Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Font E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Spigel D. O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC. Journal For ImmunoTherapy Of Cancer 2020, 8: a1. DOI: 10.1136/lba2019.1.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPrimary endpointArm APD-L1Interim overall survival analysisTumor PD-L1 statusPD-L1/PDCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsFirst-line treatmentPD-L1 statusPhase III studyPlatinum-based chemotherapyWT populationOverall survival analysisDeclaration of HelsinkiAttractive treatment choiceAtezolizumab monotherapyAUC 5AUC 6CPI monotherapyECOG PS
2019
LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study
Herbst R, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Zou W, Enquist I, Komatsubara K, Deng Y, Kuriki H, Spigel D, Jassem J. LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study. Annals Of Oncology 2019, 30: xi62-xi63. DOI: 10.1093/annonc/mdz453.Peer-Reviewed Original ResearchBlood tumor mutational burdenBiomarker-evaluable populationTumor proportion scorePD-L1Bristol-Myers SquibbClinical trialsF. Hoffmann-La RocheLecture feesAstra ZenecaBoehringer IngelheimHoffmann-La RocheOS HRBiomarker subgroupsPD-L1 IHC assaysPD-L1 immunohistochemistry assaysIHC assaysEli LillyPrincipal investigatorECOG PS 0Genentech/RochePD-L1 cutoffsSignificant OS improvementStage IV NSCLCAstellas PharmaTumor mutational burden1589TiP 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 ageLBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC
Spigel D, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Herbst R. LBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Annals Of Oncology 2019, 30: v915. DOI: 10.1093/annonc/mdz293.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPD-L1F. Hoffmann-La RocheBristol-Myers SquibbHoffmann-La RocheBoehringer IngelheimArm ACisplatin 75mg/m2Interim overall survival analysisTumor PD-L1 statusTumor-infiltrating immune cellsPD-L1/PDEli LillyCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsPD-L1 statusFirst-line treatmentPhase III studyPlatinum-based chemotherapyOverall survival analysisRoche/GenentechBristol-Meyers SquibbBiomarker-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 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 ageInterim safety and clinical activity in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus pembrolizumab (P).
Chau I, Bendell J, Calvo E, Santana-Davila R, Rodon Ahnert J, Penel N, Arkenau H, Yang J, Rege J, Mi G, Ferry D, Herbst R, Fuchs C. Interim safety and clinical activity in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus pembrolizumab (P). Journal Of Clinical Oncology 2017, 35: 102-102. DOI: 10.1200/jco.2017.35.4_suppl.102.Peer-Reviewed Original ResearchTreatment-related AEsCohort APD-L1GEJ adenocarcinomaPhase 1a/b trialECOG PS 0Treatment-related deathsDisease control rateNew safety signalsPhase 1 studyGastroesophageal junction adenocarcinomaBaseline tumor tissuePreliminary efficacy dataECOG PSMeasurable diseaseMedian PFSAdvanced gastricMaculopapular rashMedian durationPS 0Systemic therapyCohort BJunction adenocarcinomaMedian agePrior progression
2009
Phase II randomized study of biomarker-directed treatment for non-small cell lung cancer (NSCLC): The BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) clinical trial program
Kim E, Herbst R, Lee J, Blumenschein G, Tsao A, Wistuba I, Alden C, Gupta S, Stewart D, Hong W. Phase II randomized study of biomarker-directed treatment for non-small cell lung cancer (NSCLC): The BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) clinical trial program. Journal Of Clinical Oncology 2009, 27: 8024-8024. DOI: 10.1200/jco.2009.27.15_suppl.8024.Peer-Reviewed Original ResearchNon-small cell lung cancerLung cancerRecurrent non-small cell lung cancerTreatment-related adverse eventsECOG PS 0Progression-free statusAdvanced lung cancerClinical trial programCell lung cancerCore needle biopsyBRAF gene mutationCyclin D1 amplificationBiomarker analysisEligible ptsEvaluable ptsPrior chemotherapyPrimary endpointAdverse eventsPS 0Pneumothorax rateTumor responseNeedle biopsyEGFR polysomyBRAF mutationsFresh biopsies