2023
A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Muñoz-Couselo E, Rodríguez-Abreu D, Boni V, Schuchter L, Cao M, Fernandez A, Wei W, Ganti A, Hauke R, Berrocal A, Iannotti N, Hsu F, Kluger H. A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1. Clinical Cancer Research 2023, 30: 74-81. PMID: 37535056, PMCID: PMC10767304, DOI: 10.1158/1078-0432.ccr-23-0475.Peer-Reviewed Original ResearchConceptsObjective response ratePhase II trialAdverse eventsPartial responseDisease progressionII trialGrade 3 adverse eventsAnti PD-1CD40 agonist antibodyElevated liver functionTreatment-related SAEsCommon adverse eventsActivation of CD40Subset of patientsFavorable safety profileAntigen presenting cellsStable diseaseMedian durationAdvanced melanomaAdditional patientsLiver functionSafety profileMetastatic melanomaPreclinical dataPresenting cells
2021
389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Felip E, Rodríguez-Abreu D, Arance A, Boni V, Linette G, Schuchter L, Gonzalez-Cao M, Iannotti N, Ganti A, Hauke R, Berrocal A, Filbert E, Kluger H. 389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2021, 9: a422-a422. DOI: 10.1136/jitc-2021-sitc2021.389.Peer-Reviewed Original ResearchAnti-PD-1 therapyMelanoma patientsMetastatic melanomaTumor PD-L1 expressionEffective anti-tumor immunityArm phase II trialCD40 agonist antibodyRefractory melanoma patientsRefractory metastatic melanomaAdvanced melanoma patientsPD-1 blockadePD-L1 expressionPhase II trialAnti-tumor immunitySubset of patientsOverall safety profileMajority of AEsOptimal therapeutic applicationReceptor binding profileInstitutional review boardClinical study teamNebraska Medical CenterOpen labelII trialTolerability profile
2020
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Eguren-Santamaria I, Sanmamed MF, Goldberg SB, Kluger HM, Idoate MA, Lu B, Corral J, Schalper KA, Herbst RS, Gil-Bazo I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clinical Cancer Research 2020, 26: 4186-4197. PMID: 32354698, DOI: 10.1158/1078-0432.ccr-20-0798.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesAdvanced non-small cell lung cancerNSCLC brain metastasesBrain metastasesPD-L1 antibodiesAnti-PD-1/PD-L1 agentsPD-1/PD-L1 blockersActive central nervous system (CNS) involvementHigh PD-L1 expressionAnti-PD-1/PD-L1 drugsCentral nervous system involvementPivotal phase III trialsActive brain metastasesCNS response ratesPD-L1 agentsPD-L1 blockersSystemic therapy combinationsNervous system involvementPD-L1 expressionPhase III trialsSubset of patientsCell lung cancerPD-L1 drugs
2017
Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients.
Sanborn R, Pishvaian M, Kluger H, Callahan M, Weise A, Lutzky J, Yellin M, Rawls T, Vitale L, Halim A, Keler T, Davis T, Rizvi N. Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients. Journal Of Clinical Oncology 2017, 35: 3007-3007. DOI: 10.1200/jco.2017.35.15_suppl.3007.Peer-Reviewed Original ResearchCRC patientsCancer patientsAnti-PD1 antibody nivolumabPD-1 inhibitor monotherapyCD8 T cell infiltrationDrug-related SAEsSerum chemokine levelsTarget lesion diametersAcute kidney injuryPD-L1 expressionPhase 2 studyAdvanced cancer patientsAnti-tumor immunityPost-treatment biopsiesSubset of patientsT cell infiltrationMotor-sensory neuropathyPhase 1 trialOptimal dosing strategiesPhase 2 cohortMajority of tumorsPhase 2 portionObjective PRsTreatment biopsiesChemokine levels
2009
Chemotherapy and biologic therapies for melanoma: do they work?
Jilaveanu LB, Aziz SA, Kluger HM. Chemotherapy and biologic therapies for melanoma: do they work? Clinics In Dermatology 2009, 27: 614-625. PMID: 19880049, DOI: 10.1016/j.clindermatol.2008.09.020.Peer-Reviewed Original ResearchConceptsResponse rateMinority of patientsSubset of patientsInterleukin-2 (IL-2) resultsImproved response ratesIncidence of melanomaIdentification of predictorsCombination of agentsUnresectable diseaseBiologic therapyOlder regimensOverall survivalStandard chemotherapyTherapeutic optionsClinical trialsNew agentsSmall molecule inhibitorsSingle agentImmune systemMonoclonal antibodiesDeath rateMelanomaMalignant melanocytesChemotherapyMolecule inhibitorsA phase II trial of dasatinib in advanced melanoma
Kluger H, Dudek A, McCann C, Rink L, Ritacco J, Adrada C, Phouyaphone N, Southard N, Sznol M. A phase II trial of dasatinib in advanced melanoma. Journal Of Clinical Oncology 2009, 27: 9010-9010. DOI: 10.1200/jco.2009.27.15_suppl.9010.Peer-Reviewed Original ResearchStarting dosePartial responseC-kitNon-cytotoxic therapiesPhase 2 trialPhase II trialSubset of patientsMelanoma cell proliferationCommon toxicitiesDaily dasatinibMucosal primaryPo bidPrior chemotherapyII trialClinical responseUnresectable melanomaAdvanced melanomaMedian agePleural effusionMinor responseGrade IITumor assessmentDose reductionPreclinical evaluationPatients
2008
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer. Clinical Cancer Research 2008, 14: 4455-4462. PMID: 18628459, PMCID: PMC5849429, DOI: 10.1158/1078-0432.ccr-07-5268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAurora Kinase BAurora KinasesBiomarkers, TumorBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleHistory, 17th CenturyHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimatePrognosisProtein Serine-Threonine KinasesTissue Array AnalysisConceptsBreast cancerB expressionAurora B expressionBreast tumorsHigh AuroraEarly-stage breast cancerHER-2/neuProgesterone receptor expressionSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradePrimary breast tumorsCy5-conjugated antibodiesPathologic variablesPrognostic roleMultivariable analysisProspective studyNuclear gradePrognostic markerReceptor expressionClinical developmentPatientsPredictive roleCancerToxicity and Activity of a Twice Daily High-dose Bolus Interleukin 2 Regimen in Patients With Metastatic Melanoma and Metastatic Renal Cell Cancer
Acquavella N, Kluger H, Rhee J, Farber L, Tara H, Ariyan S, Narayan D, Kelly W, Sznol M. Toxicity and Activity of a Twice Daily High-dose Bolus Interleukin 2 Regimen in Patients With Metastatic Melanoma and Metastatic Renal Cell Cancer. Journal Of Immunotherapy 2008, 31: 569-576. PMID: 18528297, DOI: 10.1097/cji.0b013e318177a4ba.Peer-Reviewed Original ResearchConceptsIL-2 regimenMetastatic melanomaNormal saline fluid bolusesMetastatic renal cell cancerNew immune modulatorsTreatment-related deathsObjective response ratePercent of patientsRetrospective chart reviewSubset of patientsIL-2 dosesIntensive care unitRenal cell cancerRenal cancer patientsSubstantial acute toxicityDevelopment of combinationsChart reviewCare unitCell cancerMelanoma patientsOncology wardFluid bolusCancer patientsImmune modulatorsMedian numberExpression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development
2007
High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer
Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM. High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer. Cancer Research 2007, 67: 2932-2937. PMID: 17409397, DOI: 10.1158/0008-5472.can-06-4511.Peer-Reviewed Original ResearchConceptsHigh HSP90 expressionBreast cancerHER2/neuHSP90 expressionEstrogen receptorHigh HER2/neuCell linesEarly-stage breast cancerHER2/neu expressionHuman tumorsLymph node involvementPrimary breast cancerSubset of patientsPopulation of patientsIndependent prognostic markerHigh nuclear gradeBreast cancer cell linesBreast cancer progressionCy5-conjugated antibodiesCancer cell linesNode involvementPathologic variablesPrognostic roleMultivariable analysisProspective study
2005
Evaluating the Expression and Prognostic Value of TRAIL-R1 and TRAIL-R2 in Breast Cancer
McCarthy MM, Sznol M, DiVito KA, Camp RL, Rimm DL, Kluger HM. Evaluating the Expression and Prognostic Value of TRAIL-R1 and TRAIL-R2 in Breast Cancer. Clinical Cancer Research 2005, 11: 5188-5194. PMID: 16033835, DOI: 10.1158/1078-0432.ccr-05-0158.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCase-Control StudiesFemaleFollow-Up StudiesGene Expression ProfilingHumansMiddle AgedMultivariate AnalysisOligonucleotide Array Sequence AnalysisPrognosisReceptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis FactorSurvival AnalysisConceptsEarly-stage breast cancerTRAIL-R2 expressionBreast cancerPrognostic valueTRAIL-R2TRAIL-R1Normal breast specimensTumor necrosis factor-related apoptosis-inducing ligand receptor 1Lymph node involvementSubset of patientsBreast cancer patientsIndependent prognostic markerTRAIL-R1 expressionNormal breast epitheliumTRAIL receptor expressionLigand receptor 1Apoptosis-inducing ligand receptor 1Adjuvant treatmentNode involvementNodal statusPathologic variablesTumor sizeCancer patientsClinical trialsPrognostic markerAutomated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer
Harigopal M, Berger AJ, Camp RL, Rimm DL, Kluger HM. Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer. Clinical Cancer Research 2005, 11: 4083-4089. PMID: 15930343, DOI: 10.1158/1078-0432.ccr-04-2191.Peer-Reviewed Original ResearchConceptsE-cadherin expressionLymph node metastasisNodal metastasisBreast cancerImproved survivalNode metastasisTissue microarrayNode-positive breast cancerInvasive ductal breast cancerHER2/neu statusAnti-invasive roleInvasive ductal tumorsNode-positive patientsDuctal breast cancerSubset of patientsGood prognostic markerAggressive tumor behaviorStrong E-cadherin expressionHigh E-cadherin expressionCy5-conjugated antibodiesDuctal tumorsMetastatic sitesPrognostic valueTumor sizePrimary tumor