2017
Phase I Trial of Triapine–Cisplatin–Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers
Kunos CA, Chu E, Makower D, Kaubisch A, Sznol M, Ivy SP. Phase I Trial of Triapine–Cisplatin–Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers. Frontiers In Oncology 2017, 7: 62. PMID: 28421163, PMCID: PMC5378786, DOI: 10.3389/fonc.2017.00062.Peer-Reviewed Original ResearchCombination regimenSolid tumor cancersI trialTumor cancersAdvanced stageRecurrent uterine cervix cancerCommon grade 3Phase II trialProgression-free survivalPhase I trialContinuous intravenous infusionUterine cervix cancerStable diseaseElectrolyte abnormalitiesII trialObjective responsePaclitaxel chemotherapyReversible anemiaIntravenous infusionMonths durationCervix cancerGrade 3Day 1Day 3Regimen
2016
Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies
Kunos CA, Chu E, Beumer JH, Sznol M, Ivy SP. Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies. Cancer Chemotherapy And Pharmacology 2016, 79: 201-207. PMID: 27878356, PMCID: PMC5226891, DOI: 10.1007/s00280-016-3200-x.Peer-Reviewed Original ResearchConceptsPhase I trialSolid tumor malignanciesI trialObjective responseTumor malignancyDaily days 1Frequent grade 3Advanced-stage malignanciesDose-finding phase I trialResultsThe MTDStable diseasePrimary endpointSecondary endpointsVulvar cancerElectrolyte abnormalitiesAdverse eventsCisplatin chemotherapyUterine cervixGrade 3Day 1Day 2Day 3PatientsMalignancyDifferent schedules
2015
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, Brahmer JR, Carvajal RD, Hammers HJ, Puzanov I, Hodi FS, Kluger HM, Topalian SL, Pardoll DM, Wigginton JM, Kollia GD, Gupta A, McDonald D, Sankar V, Sosman JA, Atkins MB. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. Journal Of Clinical Oncology 2015, 33: 2013-2020. PMID: 25800770, PMCID: PMC4517051, DOI: 10.1200/jco.2014.58.1041.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Renal CellCohort StudiesDisease-Free SurvivalDose-Response Relationship, DrugFemaleHumansKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedNivolumabPatient SafetyProgrammed Cell Death 1 ReceptorTime FactorsTreatment OutcomeConceptsAdvanced renal cell carcinomaRenal cell carcinomaLong-term safetyOverall survivalDurable responsesTreatment-refractory solid tumorsTreatment-related adverse eventsOngoing randomized clinical trialsImpact of nivolumabMedian overall survivalMedian response durationPortion of patientsDuration of responseRandomized clinical trialsDrug discontinuationIntravenous nivolumabStable diseaseExpansion cohortTreatment discontinuationAdverse eventsObjective responseAdditional patientsAntibody nivolumabCell surface moleculesCell carcinomaNivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial
Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology 2015, 16: 375-384. PMID: 25795410, DOI: 10.1016/s1470-2045(15)70076-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCTLA-4 AntigenDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleHumansIpilimumabMaleMelanomaMiddle AgedNeoplasm StagingNivolumabPaclitaxelProto-Oncogene Proteins B-rafConceptsPhase 3 trialObjective responseAdvanced melanomaBRAF inhibitorsPrimary endpointAdverse eventsGrade 3Human IgG4 PD-1 immune checkpoint inhibitor antibodyDrug-related serious adverse eventsICC groupImmune checkpoint inhibitor antibodyCheckpoint inhibitor antibodyDurable objective responsesLater-line treatmentNivolumab-treated patientsSafety of nivolumabTreatment-related deathsUnacceptable toxic effectsSerious adverse eventsProportion of patientsFirst interim analysisNew treatment optionsBest overall responseDose of treatmentHigh unmet need
2014
Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2014, 32: 1020-1030. PMID: 24590637, PMCID: PMC4811023, DOI: 10.1200/jco.2013.53.0105.Peer-Reviewed Original ResearchConceptsLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2013
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal Of Medicine 2013, 369: 122-133. PMID: 23724867, PMCID: PMC5698004, DOI: 10.1056/nejmoa1302369.Peer-Reviewed Original ResearchConceptsObjective response ratePhase 1 trialAdverse eventsConcurrent therapyAdvanced melanomaTumor regressionClinical activityGrade 3Distinct immunologic mechanismsManageable safety profileProlongs overall survivalDurable tumor regressionSupportive preclinical dataRegimen groupImmunologic mechanismsObjective responseOverall survivalIntravenous dosesSafety profileTumor reductionPreclinical dataIpilimumabNivolumabPatientsMaximum doses
2012
Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New England Journal Of Medicine 2012, 366: 2443-2454. PMID: 22658127, PMCID: PMC3544539, DOI: 10.1056/nejmoa1200690.Peer-Reviewed Original ResearchConceptsAnti-PD-1 antibodyCell lung cancerRenal cell cancerObjective responseLung cancerAdverse eventsPD-L1Drug-related adverse eventsPD-1 ligand expressionCastration-resistant prostate cancerImmune-related causesPretreatment tumor specimensAdverse event profilePD-L1 expressionPD-1-PDCumulative response rateBMS-936558Immune correlatesL1 pathwayAdvanced melanomaComplete responseDeath-1PD-1Negative tumorsPositive tumors
2010
Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies
Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies. Seminars In Oncology 2010, 37: 508-516. PMID: 21074066, DOI: 10.1053/j.seminoncol.2010.09.008.Peer-Reviewed Original ResearchConceptsDurable objective responsesPotent cellular immunityAnti-CD137 antibodyCellular immune responsesLigand PD-L1Reasonable safety profileSevere liver toxicityTumor response criteriaTransplantable murine tumorsDose-dependent effectSurface of antigenImmunostimulatory mAbsAntitumor immunityObjective responseDeath-1PD-L1Tumor immunityCellular immunitySafety profileLiver toxicityClinical activityT lymphocytesImmune responseTumor antigensAgonist antibody
2004
Phase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion
Wadler S, Makower D, Clairmont C, Lambert P, Fehn K, Sznol M. Phase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion. Journal Of Clinical Oncology 2004, 22: 1553-1563. PMID: 15117978, DOI: 10.1200/jco.2004.07.158.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous continuous infusionContinuous infusionPreclinical tumor model systemsPhase II dosesStabilization of diseaseHepatic adverse eventsMaximum-tolerated dosePhase II dosePhase II trialPhase I trialAccelerated titration designPharmacokinetic studySerum tumor markersSubstantial inter-patient variabilityAbnormal organ functionDetailed pharmacokinetic studiesTumor model systemsInter-patient variabilityStable diseaseII trialObjective responseAdverse eventsI trialAdvanced cancer
2003
Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia
Giles FJ, Fracasso PM, Kantarjian HM, Cortes JE, Brown RA, Verstovsek S, Alvarado Y, Thomas DA, Faderl S, Garcia-Manero G, Wright LP, Samson T, Cahill A, Lambert P, Plunkett W, Sznol M, DiPersio JF, Gandhi V. Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia. Leukemia Research 2003, 27: 1077-1083. PMID: 12921943, DOI: 10.1016/s0145-2126(03)00118-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overDeoxyadenine NucleotidesDeoxyguanine NucleotidesDNADNA, NeoplasmEnzyme InhibitorsFemaleHumansInfusions, IntravenousLeukemia, LymphoidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocyte CountMaleMiddle AgedPyridinesRibonucleotide ReductasesSafetyThiosemicarbazonesConceptsDose-limiting toxicityNovel ribonucleotide reductase inhibitorDay 1Ribonucleotide reductase inhibitorReductase inhibitorsWhite blood cell countPhase IContinuous intravenous infusionBlood cell countWarrants further studyObjective responseRefractory leukemiaStarting doseAdvanced leukemiaIntravenous infusionH infusionSecond infusionHematologic malignanciesPlasma concentrationsPharmacodynamic studiesPharmacodynamic dataPatientsSecond courseDay 8H beginning