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 responseOverall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A.
Reckamp K, Redman M, Dragnev K, Villaruz L, Faller B, Al Baghdadi T, Hines S, Qian L, Minichiello K, Gandara D, Kelly K, Herbst R. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A. Journal Of Clinical Oncology 2022, 40: 9004-9004. DOI: 10.1200/jco.2022.40.16_suppl.9004.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerProgression-free survivalOverall survivalCell lung cancerProgressive diseaseLung cancerLung-MAPImmune checkpoint inhibitor therapyPlatinum-based doublet therapyRandomized phase II trialVEGF receptor inhibitionCheckpoint inhibitor therapyImproved overall survivalPD-L1 expressionPhase II trialPotential survival benefitDuration of responseLog-rank testStandard of careTumor mutational burdenMajor unmet needAnalysis of survivalMultiple tumor typesCare arm
2021
Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non-small cell lung cancer previously treated with a checkpoint inhibitor: Toxicity update (Lung-MAP non-matched sub-study S1800A).
Reckamp K, Redman M, Dragnev K, Villaruz L, Faller B, Al Baghdadi T, Hines S, Qian L, Minichiello K, Gandara D, Herbst R, Kelly K. Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non-small cell lung cancer previously treated with a checkpoint inhibitor: Toxicity update (Lung-MAP non-matched sub-study S1800A). Journal Of Clinical Oncology 2021, 39: 9075-9075. DOI: 10.1200/jco.2021.39.15_suppl.9075.Peer-Reviewed Original ResearchVascular endothelial growth factorThromboembolic eventsAdvanced non-small cell lung cancerNon-small cell lung cancerPlatinum-based doublet therapyPD-L1 inhibitor therapyGrade 5 AEsTreatment-related AEsVEGF receptor inhibitionGrade 3 toxicityAdverse event profilePD-L1 expressionAdverse event assessmentCell lung cancerDuration of responseTumor immune microenvironmentStandard of carePhase IIEndothelial growth factorMultiple tumor typesCare armCommon AEsECOG 0Checkpoint inhibitorsDoublet therapy
2019
LBA79 Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and -042 trials
Herbst R, Lopes G, Kowalski D, Nishio M, Wu Y, de Castro G, Baas P, Kim D, Gubens M, Cristescu R, Aurora-Garg D, Albright A, Ayers M, Loboda A, Lunceford J, Kobie J, Lubiniecki G, Pietanza M, Piperdi B, Mok T. LBA79 Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and -042 trials. Annals Of Oncology 2019, 30: v916-v917. DOI: 10.1093/annonc/mdz394.077.Peer-Reviewed Original ResearchBristol-Myers SquibbTissue TMBGenentech/RocheSubsidiary of MerckDohme Corp.KEYNOTE-010KEYNOTE-042PD-L1Merck SeronoBoehringer IngelheimMerck SharpAdvanced NSCLCClinical outcomesEli LillyOno PharmaceuticalCox proportional hazards modelPositive advanced NSCLCResults Baseline characteristicsSubset of ptsOpen-label trialTotal study populationProportional hazards modelRoche/GenentechMultiple tumor typesWhole-exome sequencing
2013
A 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
2012
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposureThe Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care
Bosserman L, Prendergast F, Herbst R, Fleisher M, Salom E, Strickland S, Raptis A, Hallquist A, Perree M, Rajurkar S, Karimi M, Rogers K, Davidson D, Willis C, Penalver M, Homesley H, Burrell M, Garrett A, Rutledge J, Chernick M, Presant CA. The Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care. Cancer Research 2012, 72: 3901-3905. PMID: 22865459, DOI: 10.1158/0008-5472.can-12-0681.Peer-Reviewed Original ResearchConceptsHigh response rateLonger survivalClinical trialsResponse rateGroup of patientsBlinded clinical trialEpithelial ovarian cancerApoptosis assaysAcute myelocytic leukemiaUnblinded clinical trialDrug developmentGeneric drug useMultiple tumor typesEfficient drug developmentCombination therapyOvarian cancerMyelocytic leukemiaClinical careTumor typesDrug useClinical therapyClinical useMolecular biomarkersDrug approvalHigher apoptosis