2022
Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non–Small-Cell Lung Cancer Previously Treated With Immunotherapy—Lung-MAP S1800A
Reckamp KL, Redman MW, Dragnev KH, Minichiello K, Villaruz LC, Faller B, Al Baghdadi T, Hines S, Everhart L, Highleyman L, Papadimitrakopoulou V, Neal J, Waqar SN, Patel JD, Gray JE, Gandara DR, Kelly K, Herbst RS. Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non–Small-Cell Lung Cancer Previously Treated With Immunotherapy—Lung-MAP S1800A. Journal Of Clinical Oncology 2022, 40: 2295-2306. PMID: 35658002, PMCID: PMC9287284, DOI: 10.1200/jco.22.00912.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionInvestigator-assessed progression-free survivalProgression-free survivalOverall survivalVascular endothelial growth factorLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerPhase II Randomized StudyTreatment-related adverse eventsRandomized phase II trialSecondary end pointsPhase II trialPlatinum-based chemotherapyCell lung cancerDuration of responseLog-rank testMajor unmet needEndothelial growth factorMultiple tumor typesAdvanced NSCLCEligible patientsOS benefitII trialObjective responseDynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab.
Gonzalez-Kozlova E, Huang H, Redman M, Herbst R, Gettinger S, Bazhenova L, Xie H, Patel M, Nie K, Harris J, Argueta K, Cerami E, Hong J, Biswas R, Van Nostrand S, Kelly K, Moravec R, Del Valle D, Kim-Schulze S, Gnjatic S. Dynamic changes in serum analyte levels associated with clinical outcome in squamous cell lung cancer trial SWOG Lung-MAP S1400I of nivolumab ± ipilimumab. Journal Of Clinical Oncology 2022, 40: 9044-9044. DOI: 10.1200/jco.2022.40.16_suppl.9044.Peer-Reviewed Original ResearchImmune checkpoint blockadeSerial blood specimensObjective responseOverall survivalLung cancerBlood specimensCox modelRecurrent squamous cell lung cancerWk 3Randomized phase III trialSquamous cell lung cancerPhase III trialsBest objective responseCell lung cancerRisk of deathProtein levelsSerum analyte levelsIndicators of outcomeLinear mixed modelsSerum protein levelsProximity extension assayMeasurement of bloodEligible patientsLower IL6Checkpoint blockade
2021
Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC
Herbst RS, Garon EB, Kim DW, Cho BC, Gervais R, Perez-Gracia JL, Han JY, Majem M, Forster MD, Monnet I, Novello S, Gubens MA, Boyer M, Su WC, Samkari A, Jensen EH, Kobie J, Piperdi B, Baas P. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC. Journal Of Thoracic Oncology 2021, 16: 1718-1732. PMID: 34048946, DOI: 10.1016/j.jtho.2021.05.001.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreAdvanced NSCLCOverall survivalPembrolizumab improved overall survivalTissue tumor mutational burdenExploratory biomarker analysisImproved overall survivalProgrammed Death LigandTumor mutational burdenDocetaxel 75KEYNOTE-010Pembrolizumab dosesPembrolizumab treatmentSurvival updateData cutoffObjective responseHazard ratioOS ratesCare treatmentLong-term benefitsMedian studyImproved outcomesPembrolizumabProportion score
2020
SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study).
Leighl N, Redman M, Rizvi N, Hirsch F, Mack P, Schwartz L, Wade J, Irvin W, Reddy S, Crawford J, Bradley J, Stinchcombe T, Ramalingam S, Miao J, Minichiello K, Gandara D, Herbst R, Papadimitrakopoulou V, Kelly K. SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study). Journal Of Clinical Oncology 2020, 38: 9623-9623. DOI: 10.1200/jco.2020.38.15_suppl.9623.Peer-Reviewed Original ResearchSquamous lung carcinomaLung carcinomaMedian PFSAdverse eventsObjective responseDisease progressionStage IV squamous cell lung cancerPD-1 checkpoint inhibitor therapySquamous cell lung cancerPD-1 checkpoint inhibitorsGood responseAdequate organ functionGrade 4 dyspneaPerformance status 0PR/SDTreatment-related deathsCheckpoint inhibitor therapyImmune-related toxicitiesPhase II studyPD-1 inhibitionBest objective responseCell lung cancerEligible patientsQ28 daysStatus 0
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
2010
A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies
Camidge DR, Herbst RS, Gordon MS, Eckhardt SG, Kurzrock R, Durbin B, Ing J, Tohnya TM, Sager J, Ashkenazi A, Bray G, Mendelson D. A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies. Clinical Cancer Research 2010, 16: 1256-1263. PMID: 20145186, DOI: 10.1158/1078-0432.ccr-09-1267.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade 3 transaminase elevationHuman IgG1 monoclonal antibodyPhase I safetyDose-escalation designDose-dependent increaseDeath receptor 5Different tumor typesIgG1 monoclonal antibodyCohort expansionTransaminase elevationI safetyMost patientsObjective responseTrough concentrationsAdverse eventsEscalation designMultiple dosesMinor responseEfficacious concentrationsOvarian cancerEvidence of activityPharmacokinetic analysisReceptor 5Human studies
2007
A phase I safety and pharmacokinetic study of apomab, a human DR5 agonist antibody, in patients with advanced cancer
Camidge D, Herbst R, Gordon M, Eckhardt S, Kurzroc R, Durbin B, Ing J, Ling J, Sager J, Mendelson D. A phase I safety and pharmacokinetic study of apomab, a human DR5 agonist antibody, in patients with advanced cancer. Journal Of Clinical Oncology 2007, 25: 3582-3582. DOI: 10.1200/jco.2007.25.18_suppl.3582.Peer-Reviewed Original ResearchTreatment-refractory solid tumorsPhase I safetyColorectal cancer patientsPre-clinical dataEvidence of benefitDR5 agonist antibodyAnti-cancer efficacyIgG1 monoclonal antibodyAsymptomatic transaminitisCohort expansionECOG PSHAHA responseUnacceptable toxicityI safetyObjective responseSymptomatic improvementAdvanced cancerCancer patientsMinor responseReceptor agonistTarget lesionsApomabDisease progressionEfficacy dataPreclinical modelsKRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II. KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer. Clinical Cancer Research 2007, 13: 2890-2896. PMID: 17504988, DOI: 10.1158/1078-0432.ccr-06-3043.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideFemaleGefitinibGene DosageHumansLung NeoplasmsMaleMiddle AgedMutationPrognosisProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTreatment OutcomeConceptsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsCell lung cancerKRAS mutationsTyrosine kinase inhibitorsEGFR-TKIEGFR copy numberEGFR mutationsLung cancerFavorable responseKinase inhibitorsShorter median timeArchival tissue specimensEGFR gene mutationsPanel of markersAdvanced NSCLCObjective responseProgressive diseaseSurvival benefitMedian timePoor responseSuch therapyDisease progressionPatients
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 response
2005
TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA. TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2005, 23: 5892-5899. PMID: 16043829, DOI: 10.1200/jco.2005.02.840.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungDisease ProgressionErbB ReceptorsErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedPaclitaxelPlacebosProtein Kinase InhibitorsQuinazolinesSurvival AnalysisConceptsUntreated advanced NSCLCOverall survivalAdvanced NSCLCObjective responseLung cancerAdvanced non-small cell lung cancerEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsNon-small cell lung cancerEnd pointReceptor tyrosine kinase inhibitorsCycles of carboplatinGood performance statusImproved overall survivalOutcomes of patientsPrimary end pointSecondary end pointsPhase III trialsSingle-agent activityCell lung cancerDuration of responseTyrosine kinase inhibitorsAssessable patientsConcurrent carboplatinErlotinib arm
2003
52 Rapid and durable objective responses in patients with advanced non-small-cell lung cancer in phase II trials (IDEAL 1 and IDEAL 2) treated with gefitinib
Gatzemeier U, Douillard J, Kris M, Fukuoka M, Herbst R, Schiller J, Wolf M, McPartiane A, Kay A, Fandi A. 52 Rapid and durable objective responses in patients with advanced non-small-cell lung cancer in phase II trials (IDEAL 1 and IDEAL 2) treated with gefitinib. European Journal Of Cancer Supplements 2003, 1: s20. DOI: 10.1016/s1359-6349(03)90087-5.Peer-Reviewed Original Research