2020
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Zamarin D, Hamid O, Nayak-Kapoor A, Sahebjam S, Sznol M, Collaku A, Fox FE, Marshall MA, Hong DS. Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study. Clinical Cancer Research 2020, 26: 4531-4541. PMID: 32586937, PMCID: PMC8375360, DOI: 10.1158/1078-0432.ccr-20-0328.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugFemaleHumansLymphocyte DepletionMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsReceptors, CCR4T-Lymphocytes, RegulatoryYoung AdultConceptsAdvanced solid tumorsDose escalationSolid tumorsCohort expansionEffector regulatory T cellsC chemokine receptor 4Phase IDose-expansion cohortsAdvanced pancreatic cancerObjective response rateMajority of patientsRegulatory T cellsChemokine receptor 4Potent antitumor efficacyMogamulizumab treatmentCheckpoint inhibitorsDose expansionExpansion cohortIntratumoral TregsPrimary endpointClinical responseEscalation studyBaseline degreePharmacodynamic profilePancreatic cancer
2017
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Sznol M, Ferrucci PF, Hogg D, Atkins MB, Wolter P, Guidoboni M, Lebbé C, Kirkwood JM, Schachter J, Daniels GA, Hassel J, Cebon J, Gerritsen W, Atkinson V, Thomas L, McCaffrey J, Power D, Walker D, Bhore R, Jiang J, Hodi FS, Wolchok JD. Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2017, 35: jco.2016.72.116. PMID: 28915085, DOI: 10.1200/jco.2016.72.1167.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansIpilimumabMaleMaximum Tolerated DoseMelanomaMiddle AgedNeoplasm InvasivenessNeoplasm StagingNivolumabPatient SafetyPrognosisRandomized Controlled Trials as TopicRetrospective StudiesSkin NeoplasmsSurvival AnalysisConceptsTreatment-related adverse eventsTreatment-related select adverse eventsSelect adverse eventsAdverse eventsImmune-modulating agentsAdvanced melanomaMedian timeSafety profileResolution rateGrade 3/4 treatment-related adverse eventsTreatment-related grade 3/4 adverse eventsGrade 3/4 adverse eventsDose of nivolumabIpilimumab combination therapyProgression-free survivalEndocrine adverse eventsAddition of nivolumabGrade 3/4AE managementMedian durationUnacceptable toxicityAntitumor responseCombination therapyStudy deathsDisease progressionResults from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
Segal NH, Logan TF, Hodi FS, McDermott D, Melero I, Hamid O, Schmidt H, Robert C, Chiarion-Sileni V, Ascierto PA, Maio M, Urba WJ, Gangadhar TC, Suryawanshi S, Neely J, Jure-Kunkel M, Krishnan S, Kohrt H, Sznol M, Levy R. Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody. Clinical Cancer Research 2017, 23: 1929-1936. PMID: 27756788, DOI: 10.1158/1078-0432.ccr-16-1272.Peer-Reviewed Original ResearchMeSH Keywords4-1BB LigandAdultAgedAntibodies, MonoclonalAntineoplastic AgentsDose-Response Relationship, DrugFemaleHumansMaleMaximum Tolerated DoseMelanomaMiddle AgedNeoplasmsConceptsTreatment-related adverse eventsAdverse eventsPharmacodynamic activityCommon treatment-related adverse eventsLiver function test abnormalitiesImmuno-oncology agentsSerious adverse eventsAdvanced solid tumorsHepatic adverse eventsClin Cancer ResSignificant transaminitisMonotherapy studiesAdvanced cancerTest abnormalitiesIFN-inducible genesStandard treatmentClinical evaluationUrelumabSafety dataAgonist antibodySolid tumorsCancer ResDoseDosesWeeks
2016
Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study
McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, Powderly JD, Infante JR, Fassò M, Wang YV, Zou W, Hegde PS, Fine GD, Powles T. Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. Journal Of Clinical Oncology 2016, 34: 833-842. PMID: 26755520, DOI: 10.1200/jco.2015.63.7421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellDose-Response Relationship, DrugDose-Response Relationship, ImmunologicFemaleHumansImmunohistochemistryKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedT-LymphocytesConceptsMetastatic renal cell carcinomaRenal cell carcinomaClinical activityCell carcinomaImmune cellsAnti-programmed death ligand 1 antibodyImmune-mediated adverse eventsNon-clear cell histologySolid Tumors version 1.1Death ligand 1 antibodyTumor-infiltrating immune cellsEnd pointFuhrman grade 4Phase Ia studyManageable safety profileObjective response ratePrimary end pointSecondary end pointsPD-L1 expressionPD-L1 stainingProgression-free survivalResponse Evaluation CriteriaEffector T cellsAcute phase proteinsGrade 4
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 carcinoma
2014
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2014, 32: 3659-3666. PMID: 25267741, PMCID: PMC4879709, DOI: 10.1200/jco.2013.54.8115.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlopeciaAntibodies, MonoclonalDose-Response Relationship, DrugDrug Administration ScheduleExanthemaFatigueFemaleHumansImmunoconjugatesMaleMelanomaMiddle AgedNeutropeniaTreatment OutcomeConceptsMaximum-tolerated doseObjective response rateGreater objective response rateGlembatumumab vedotinAdvanced melanomaGrade 3/4 treatment-related toxicitiesHuman immunoglobulin G2 monoclonal antibodyPhase I/II studyPhase II expansion cohortPromising objective response ratesEnd pointTreatment-related deathsPrimary end pointSecondary end pointsTreatment-related toxicityProgression-free survivalPhase II expansionMonomethyl auristatin E.Stable diseaseExpansion cohortII studyPartial responseDose escalationMore patientsFrequent dosing
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
PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells
Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker JP, Kluger Y, Sznol M. PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells. Pigment Cell & Melanoma Research 2010, 23: 190-200. PMID: 20149136, PMCID: PMC2848976, DOI: 10.1111/j.1755-148x.2010.00685.x.Peer-Reviewed Original ResearchConceptsMelanoma cellsTumor cellsMelanoma tumor cellsPrimary melanoma cellsMetastatic tumor cellsStatus of mutationsClinical responseRate of proliferationAdvanced lesionsInhibitor PLX4032Kinase inhibitorsPLX4032ERK pathwayCell migrationNRASDownstream effectorsCell adherenceERK1/2CellsProliferationCell cycle controlMobility of cellsActive ERK1/2Therapy
2007
Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies
Gojo I, Tidwell ML, Greer J, Takebe N, Seiter K, Pochron MF, Johnson B, Sznol M, Karp JE. Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies. Leukemia Research 2007, 31: 1165-1173. PMID: 17324462, DOI: 10.1016/j.leukres.2007.01.004.Peer-Reviewed Original ResearchConceptsHematologic malignanciesDay 1White blood cell countPhase IAdvanced hematologic malignanciesBlood cell countPeak plasma concentrationPre-clinical modelsAnti-leukemia activityPotent ribonucleotide reductase inhibitorWarrants further investigationAdvanced leukemiaH infusionPlasma concentrationsDose levelsRibonucleotide reductase inhibitorCell countReductase inhibitorsPharmacokinetic studyMalignancyGrowth inhibitionFurther investigationPotent inhibitorAdultsDays
2006
Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome
Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O’Brien S, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research 2006, 30: 813-822. PMID: 16478631, DOI: 10.1016/j.leukres.2005.12.013.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDose-Response Relationship, DrugDrug Administration ScheduleDrug CombinationsFemaleHumansInjections, IntravenousLeukemia, MyeloidMaleMaximum Tolerated DoseMiddle AgedMyelodysplastic SyndromesPyridinesRecurrenceRisk FactorsThiosemicarbazonesTreatment OutcomeConceptsAra-C dose levelsDose levelsM2/dayAcute leukemiaSignificant anti-leukemia activityConsecutive daysPhase II regimenRefractory acute leukemiaHigh-risk MDSAnti-leukemia activityEvaluable patientsMyelodysplastic syndromeActive combinationPatientsPhase IIron chelatorsLeukemiaAraPotent inhibitorDaysTriapineRegimenCytarabineInfusionSyndrome
2005
Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12
Eisenbeis CF, Lesinski GB, Anghelina M, Parihar R, Valentino D, Liu J, Nadella P, Sundaram P, Young DC, Sznol M, Walker MJ, Carson WE. Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12. Journal Of Clinical Oncology 2005, 23: 8835-8844. PMID: 16314644, DOI: 10.1200/jco.2005.02.1691.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugHumansInterferon alpha-2Interferon-alphaInterferon-gammaInterleukin-12Leukocytes, MononuclearMiddle AgedNeoplasmsRecombinant ProteinsSignal TransductionSTAT1 Transcription FactorTime FactorsTreatment OutcomeConceptsPatients' peripheral blood mononuclear cellsPatient PBMCsInterferon alfa-2bIFN-gammaInterleukin-12Alfa-2bRhIL-12Advanced cancerIL-12Greater IFN-gamma productionPeripheral blood mononuclear cellsPeak levelsIL-12 administrationPlasma IFN-gammaIL-12 therapyDose-limiting toxicityIFN-gamma productionHuman interleukin-12Interferon Signaling PathwayAssessable patientsIntracellular STAT1Stable diseasePeripheral bloodMononuclear cellsLevels of STAT1Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation
Thamm DH, Kurzman ID, King I, Li Z, Sznol M, Dubielzig RR, Vail DM, MacEwen EG. Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation. Clinical Cancer Research 2005, 11: 4827-4834. PMID: 16000580, DOI: 10.1158/1078-0432.ccr-04-2510.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial VaccinesDiarrheaDog DiseasesDogsDose-Response Relationship, DrugFemaleFeverMaleNeoplasmsSalmonella typhimuriumTreatment OutcomeVaccines, AttenuatedVomitingConceptsAntitumor responseTumor tissueAntitumor activityMajor antitumor responsesTumor-bearing dogsDose-limiting toxicityInherent antitumor activitySignificant antitumor activityRefractory feverDisease stabilizationEscalation trialFirst infusionShort-term toxicityIncisional biopsyClinicopathologic variablesSystemic administrationTumor targeting capacityMalignant tumorsAcute deathSpontaneous tumorsSpontaneous neoplasiaPowerful anticancer therapySalmonella typhimuriumVital signsPhase IA phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer
Murren J, Modiano M, Kummar S, Clairmont C, Egorin M, Chu E, Sznol M. A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer. Investigational New Drugs 2005, 23: 123-135. PMID: 15744588, DOI: 10.1007/s10637-005-5857-6.Peer-Reviewed Original ResearchConceptsPhase II trialDose levelsII trialVNP40101MGrade 2 adverse eventsIntra-patient dose escalationPre-treated patient populationBroad anti-tumor activityGrade 3 thrombocytopeniaPhase I trialPeak plasma concentrationDose-related toxicityMurine tumor modelsAnti-tumor activityModerate granulocytopeniaAcute headacheStarting doseAdverse eventsI trialMajor toxicityDose escalationFacial flushingPatient populationPlasma concentrationsMetastatic cancer
2003
Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors.
Murren J, Modiano M, Clairmont C, Lambert P, Savaraj N, Doyle T, Sznol M. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clinical Cancer Research 2003, 9: 4092-100. PMID: 14519631.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAdverse eventsSafety profilePhase IGrade 3Week scheduleDrug-related adverse eventsGrade 2 adverse eventsGrade 1Common nonhematological toxicitiesGrade 4 leukopeniaSingle-patient cohortsAcceptable safety profileAdvanced solid tumorsDose-escalation phaseHepatic adverse eventsPhase II trialCohort of patientsCumulative urinary recoveryLinear pharmacokinetic behaviorPotent ribonucleotide reductase inhibitorNonhematological toxicitiesII trialMean eliminationStarting dose