2021
Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma
Diab A, Tykodi SS, Daniels GA, Maio M, Curti BD, Lewis KD, Jang S, Kalinka E, Puzanov I, Spira AI, Cho DC, Guan S, Puente E, Nguyen T, Hoch U, Currie SL, Lin W, Tagliaferri MA, Zalevsky J, Sznol M, Hurwitz ME. Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2914-2925. PMID: 34255535, PMCID: PMC8425826, DOI: 10.1200/jco.21.00675.Peer-Reviewed Original ResearchConceptsProgression-free survivalImmune-mediated adverse eventsMedian progression-free survivalObjective response rateMetastatic melanomaOverall survivalResponse rateAdverse eventsTarget lesionsGrade 3Stage III/IV melanomaEnd pointPhase II cohortComplete response rateMedian overall survivalPrimary end pointRadiologic evidenceUntreated patientsDurable responsesPolyfunctional responsesOS ratesBlood biomarkersComplete clearanceMedian changeExploratory biomarkersMolecular correlates of response to nivolumab at baseline and on treatment in patients with RCC
Ross-Macdonald P, Walsh AM, Chasalow SD, Ammar R, Papillon-Cavanagh S, Szabo PM, Choueiri TK, Sznol M, Wind-Rotolo M. Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Journal For ImmunoTherapy Of Cancer 2021, 9: e001506. PMID: 33658305, PMCID: PMC7931766, DOI: 10.1136/jitc-2020-001506.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellCD4 AntigensCD8 AntigensCytokinesDrug Resistance, NeoplasmHumansImmune Checkpoint InhibitorsKidney NeoplasmsLymphocytes, Tumor-InfiltratingMutationNivolumabProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellTime FactorsT-LymphocytesTreatment OutcomeConceptsClear cell renal cell carcinomaMetastatic clear cell renal cell carcinomaT cell infiltrationNivolumab responseExact testDeath ligand 1 (PD-L1) statusFirst-line treatment decisionsT-cell receptor clonalitySerum cytokine assaysImmune checkpoint inhibitorsNon-responding patientsDeath-1 receptorCell renal cell carcinomaSubset of patientsRenal cell carcinomaFisher's exact testWnt/β-cateninLogistic regression modelsRank sum testCD8 statusCheckpoint inhibitorsIndex lesionPatient selectionTCR clonalityCell carcinoma
2017
Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study
Callahan MK, Kluger H, Postow MA, Segal NH, Lesokhin A, Atkins MB, Kirkwood JM, Krishnan S, Bhore R, Horak C, Wolchok JD, Sznol M. Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. Journal Of Clinical Oncology 2017, 36: jco.2017.72.285. PMID: 29040030, PMCID: PMC5946731, DOI: 10.1200/jco.2017.72.2850.Peer-Reviewed Original ResearchConceptsPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyDose-escalation studyAdvanced melanomaOverall survivalAdverse eventsOS ratesClinical activityGrade 3Common grade 3Doses of nivolumabDurable clinical activityModified WHO criteriaNivolumab Plus IpilimumabTreatment-related deathsUntreated advanced melanomaImmune checkpoint inhibitorsMedian overall survivalObjective response rateLong-term followSubsequent clinical developmentConcurrent nivolumabCheckpoint inhibitorsExpansion cohortOverall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator’s Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial
Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH, Gutzmer R, Linette G, Chmielowski B, Lao CD, Lorigan P, Grossmann K, Hassel JC, Sznol M, Daud A, Sosman J, Khushalani N, Schadendorf D, Hoeller C, Walker D, Kong G, Horak C, Weber J. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator’s Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. Journal Of Clinical Oncology 2017, 36: jco.2016.71.802. PMID: 28671856, PMCID: PMC6804912, DOI: 10.1200/jco.2016.71.8023.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdultAgedAged, 80 and overAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinDacarbazineDisease ProgressionDrug Administration ScheduleFemaleHumansMaleMelanomaMiddle AgedNivolumabPaclitaxelProgression-Free SurvivalSkin NeoplasmsTime FactorsYoung AdultConceptsInvestigator-choice chemotherapyAdvanced melanomaAnti-programmed death-1 (PD-1) agentsOpen-label phase III trialMedian progression-free survivalResults Two hundred seventyTreatment-related adverse eventsIpilimumab-refractory patientsNivolumab-treated patientsPhase III trialsProgression-free survivalProportion of patientsPoor prognostic factorOverall response rateLactate dehydrogenase levelsSurvival end pointsConclusion NivolumabMedian OSNivolumab groupBrain metastasesChemotherapy regimensUnacceptable toxicityAdverse eventsDurable responsesIII trials
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
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 STAT1Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia
Giles F, Verstovsek S, Thomas D, Gerson S, Cortes J, Faderl S, Ferrajoli A, Ravandi F, Kornblau S, Garcia-Manero G, Jabbour E, O'Brien S, Karsten V, Cahill A, Yee K, Albitar M, Sznol M, Kantarjian H. Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia. Clinical Cancer Research 2005, 11: 7817-7824. PMID: 16278404, DOI: 10.1158/1078-0432.ccr-05-1070.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlkylating AgentsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBase Pair MismatchCohort StudiesCytarabineDisease ProgressionDNADNA RepairFemaleHumansHydrazinesLeukemiaLeukocytes, MononuclearMaleMiddle AgedModels, ChemicalO(6)-Methylguanine-DNA MethyltransferaseSulfonamidesTime FactorsConceptsContinuous infusionAGT activityAra-C regimenSignificant antileukemia activityPredictors of responseAcute myeloid leukemiaCourse of treatmentGm/Significant antileukemic activityEvaluable patientsNovel sulfonylhydrazineRefractory diseaseRefractory leukemiaStarting doseComplete responseDose schedulePatient subsetsMyeloid leukemiaPatientsAlkylguanine-DNA alkyltransferaseDose levelsDay 2Antileukemia activityAntileukemic activityCloretazine