2022
Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors
Sanborn RE, Pishvaian MJ, Callahan MK, Weise A, Sikic BI, Rahma O, Cho DC, Rizvi NA, Sznol M, Lutzky J, Bauman JE, Bitting RL, Starodub A, Jimeno A, Reardon DA, Kaley T, Iwamoto F, Baehring JM, Subramaniam DS, Aragon-Ching JB, Hawthorne TR, Rawls T, Yellin M, Keler T. Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2022, 10: e005147. PMID: 35940825, PMCID: PMC9364417, DOI: 10.1136/jitc-2022-005147.Peer-Reviewed Original ResearchConceptsObjective response rateAnti-PD-1/L1Solid tumorsAnti-PD-1 therapyIntratumoral T cell infiltrationBetter progression-free survivalAnti-CD27 antibodyKey clinical endpointsTumor PD-L1Tumor-specific cohortsAdvanced solid tumorsProgression-free survivalRefractory solid tumorsOverall survival rateT cell infiltrationBetter clinical outcomesSquamous cell carcinomaOvarian cancer patientsPhase 2Phase 1Nivolumab monotherapyAdverse eventsImmune signaturesPD-L1Proinflammatory changesFirst-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors
Kim TW, Burris HA, de Miguel Luken MJ, Pishvaian MJ, Bang YJ, Gordon M, Awada A, Camidge DR, Hodi FS, McArthur GA, Miller WH, Cervantes A, Chow LQ, Lesokhin AM, Rutten A, Sznol M, Rishipathak D, Chen SC, Stefanich E, Pourmohamad T, Anderson M, Kim J, Huseni M, Rhee I, Siu LL. First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2022, 28: of1-of12. PMID: 35699599, PMCID: PMC9662912, DOI: 10.1158/1078-0432.ccr-21-4020.Peer-Reviewed Original ResearchConceptsAdverse eventsImmune activationT cellsMost common treatment-related adverse eventsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsRenal cell carcinoma patientsNon-small cell lung carcinomaRegulatory T cell functionTriple-negative breast cancerPD-1/PD-L1 antagonistsDose-escalation stageInfusion-related reactionsAdvanced solid tumorsRefractory solid tumorsCell carcinoma patientsDose-limiting toxicityEffector T cellsSubset of patientsFavorable safety profileHuman phase IPD-L1 antagonistsT cell functionCell lung carcinomaBempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study
Tannir NM, Cho DC, Diab A, Sznol M, Bilen MA, Balar AV, Grignani G, Puente E, Tang L, Chien D, Hoch U, Choudhury A, Yu D, Currie SL, Tagliaferri MA, Zalevsky J, Siefker-Radtke AO, Hurwitz ME. Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study. Journal For ImmunoTherapy Of Cancer 2022, 10: e004419. PMID: 35444058, PMCID: PMC9021810, DOI: 10.1136/jitc-2021-004419.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRenal cell carcinomaProgression-free survivalAdvanced clear cell renal cell carcinomaClear cell renal cell carcinomaFirst-line therapyOverall survivalCell carcinomaGrade 3/4 treatment-related adverse eventsSingle-arm phase 1/2 studyMedian progression-free survivalMedian overall survivalObjective response ratePhase 1/2 studyCent of patientsPreliminary antitumor activitySingle-arm designAdverse eventsComplete responseBaseline biomarkersTreatment optionsExploratory biomarkersRCC cohortBempegaldesleukinNivolumabT cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma
Lozano AX, Chaudhuri AA, Nene A, Bacchiocchi A, Earland N, Vesely MD, Usmani A, Turner BE, Steen CB, Luca BA, Badri T, Gulati GS, Vahid MR, Khameneh F, Harris PK, Chen DY, Dhodapkar K, Sznol M, Halaban R, Newman AM. T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma. Nature Medicine 2022, 28: 353-362. PMID: 35027754, PMCID: PMC8866214, DOI: 10.1038/s41591-021-01623-z.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune-related adverse eventsT-cell characteristicsIrAE developmentBlood samplesSevere immune-related adverse eventsAnti-PD-1 monotherapyCombination immune checkpoint inhibitorsT-cell receptor sequencingT cell abundanceCell receptor sequencingOrgan system involvementPeripheral blood samplesIrAE onsetCheckpoint inhibitorsAdverse eventsCheckpoint blockadeRNA sequencingTCR clonalityCombination therapyPatient cohortSystem involvementClinical managementTCR diversityImmunological stateAutoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review
Heng JS, Kim JM, Jones DK, Stoessel KM, Weiss SA, Sznol M, Kluger HM, Walter SD, Silverstein NA, Pointdujour-Lim R. Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review. BMJ Open Ophthalmology 2022, 7: e000889. PMID: 35047671, PMCID: PMC8724805, DOI: 10.1136/bmjophth-2021-000889.Peer-Reviewed Original ResearchConceptsAdvanced cutaneous melanomaAnti-retinal antibodiesImmune-related adverse eventsAutoimmune retinopathyCutaneous melanomaNivolumab immunotherapySystematic reviewAdverse eventsMucosal melanomaAcute exudative polymorphous vitelliform maculopathyPotential immune-related adverse eventsBilateral visual field lossNew visual symptomsImmune checkpoint inhibitionRetrospective chart reviewCutaneous melanoma patientsVaried clinical manifestationsVisual field lossComplete ophthalmic examinationScreening of patientsMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsVitelliform maculopathyChart reviewFunduscopic changes
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 biomarkersA Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2020
Safety and efficacy of combination nivolumab plus ipilimumab in patients with advanced melanoma: results from a North American expanded access program (CheckMate 218)
Hodi FS, Chapman PB, Sznol M, Lao CD, Gonzalez R, Smylie M, Daniels GA, Thompson JA, Kudchadkar R, Sharfman W, Atkins M, Spigel DR, Pavlick A, Monzon J, Kim KB, Ernst S, Khushalani NI, van Dijck W, Lobo M, Hogg D. Safety and efficacy of combination nivolumab plus ipilimumab in patients with advanced melanoma: results from a North American expanded access program (CheckMate 218). Melanoma Research 2020, 31: 67-75. PMID: 33234846, PMCID: PMC7757740, DOI: 10.1097/cmr.0000000000000708.Peer-Reviewed Original ResearchConceptsAdvanced melanomaEastern Cooperative Oncology Group performance statusUnresectable stage III/IV melanomaStage III/IV melanomaTreatment-related adverse eventsElevated lactate dehydrogenase levelBRAF wild-type tumorsOverall survival dataRandomized clinical trialsLactate dehydrogenase levelsAccess programBRAF-mutant tumorsRelevant patient subgroupsWild-type tumorsCombination nivolumabEligible patientsOS ratesCheckpoint inhibitorsTreatment discontinuationAdverse eventsPerformance statusUnacceptable toxicityMucosal melanomaPatient subgroupsClinical trialsTebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma
Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR, Steven NM, Evans TRJ, Anthoney A, Shoushtari AN, Hamid O, Gupta A, Vardeu A, Leach E, Naidoo R, Stanhope S, Lewis S, Hurst J, O’Kelly I, Sznol M. Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Clinical Cancer Research 2020, 26: 5869-5878. PMID: 32816891, PMCID: PMC9210997, DOI: 10.1158/1078-0432.ccr-20-1247.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAtaxia Telangiectasia Mutated ProteinsCD3 ComplexCD8-Positive T-LymphocytesCell ProliferationChemokine CXCL10Cytotoxicity, ImmunologicDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticGp100 Melanoma AntigenHumansImmunityInterferon-gammaMaleMelanomaMiddle AgedNeoplasm ProteinsReceptors, Antigen, T-CellReceptors, CXCR3Recombinant Fusion ProteinsTumor MicroenvironmentConceptsT cellsBispecific fusion proteinMetastatic melanomaT cell receptorSerum CXCL10Multicenter phase I/II trialPhase I/II trialTreatment-related adverse eventsHigh-affinity T-cell receptorsAppearance of rashMetastatic cutaneous melanomaAntitumor immune responseOverall survival rateMetastatic uveal melanomaCytotoxic T cellsPathway-related markersTumor biopsy samplesMechanism of actionII trialAdverse eventsAdvanced melanomaBroad therapeutic potentialPatient survivalPatient cohortCutaneous melanoma
2019
Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma
Regan MM, Werner L, Rao S, Gupte-Singh K, Hodi FS, Kirkwood JM, Kluger HM, Larkin J, Postow MA, Ritchings C, Sznol M, Tarhini AA, Wolchok JD, Atkins MB, McDermott DF. Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma. Journal Of Clinical Oncology 2019, 37: 3350-3358. PMID: 31498030, PMCID: PMC6901280, DOI: 10.1200/jco.19.00345.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsTreatment-free survivalHigher treatment-related adverse eventsKaplan-Meier curvesTherapy initiationAdvanced melanomaICI therapyEnd pointGrade 3Outcome measuresLonger treatment-free survivalImmuno-oncology agentsSystemic therapy initiationThird end pointTreatment-free timeImmune checkpoint inhibitionSurvival end pointsEvent end pointsNovel outcome measuresCheckMate 067ICI cessationAdverse eventsTherapy cessationCheckpoint inhibitionPooled analysis
2018
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial
Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, Weiss SA, Cohen JV, Yu J, Hegde U, Perrotti E, Anderson G, Ralabate A, Kluger Y, Wei W, Goldberg SB, Jilaveanu LB. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Journal Of Clinical Oncology 2018, 37: 52-60. PMID: 30407895, PMCID: PMC6354772, DOI: 10.1200/jco.18.00204.Peer-Reviewed Original ResearchConceptsBrain metastasis responseBrain metastasesMetastasis responseAdverse eventsAnti-programmed cell death-1 (PD-1) agentsDeath ligand 1 (PD-L1) expressionModified Response Evaluation CriteriaPhase II clinical trialActive brain metastasesAsymptomatic brain metastasesCD8 cell densityNeurologic adverse eventsPembrolizumab-treated patientsUse of pembrolizumabMelanoma brain metastasesPrimary end pointLigand 1 expressionPhase II trialResponse Evaluation CriteriaT-cell infiltratesUntreated brain metastasesDeath ligand 1Two-year survivalOverall survival timeResult of progressionCollateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 2018, 67: dbi180002. PMID: 29937434, PMCID: PMC6054443, DOI: 10.2337/dbi18-0002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalAutoimmune DiseasesB7-H1 AntigenDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseGenotypeHLA-DR4 AntigenHumansHypoglycemic AgentsInsulinInsulin SecretionIsoantibodiesKetosisModels, ImmunologicalNeoplasmsPancreasPancreatitisProgrammed Cell Death 1 ReceptorConceptsInsulin-dependent diabetesCheckpoint inhibitorsAdverse eventsHLA-DR4Classic type 1 diabetesPD-L1 checkpoint inhibitorsEvidence of pancreatitisImmune adverse eventsSolid organ cancersType 1 diabetesPeridiagnosis periodPositive autoantibodiesL1 antibodyInsulin-DependentHigh riskPatientsDiabetesCancerInhibitorsKetoacidosisAutoimmuneAutoantibodiesPancreatitisComplicationsSyndromeFirst-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discovery 2018, 8: 184-195. PMID: 29247021, DOI: 10.1158/2159-8290.cd-17-1119.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMutationNeoplasm StagingNeoplasmsProtein Kinase InhibitorsPyrrolesTomography, X-Ray ComputedTreatment OutcomeYoung AdultConceptsCommon treatment-related adverse eventsSolid tumorsHuman dose-escalation studyMulticenter phase I trialTreatment-related adverse eventsDose-escalation cohortsDose-expansion cohortsMutant solid tumorsPhase II doseAcceptable safety profileAdvanced solid tumorsDose-escalation studyPhase I trialPotent preclinical activityTreatment of patientsSolid tumor malignanciesERK1/2 kinase inhibitorEvaluable patientsDose expansionExpansion cohortAdverse eventsPartial responseDose escalationI trialSafety profile
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 cohortPooled 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 progressionPhase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors
Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors. Clinical Cancer Research 2017, 23: 5349-5357. PMID: 28634283, DOI: 10.1158/1078-0432.ccr-17-1243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyDiagnostic ImagingDrug MonitoringFemaleHumansImmunoglobulin GMaleMaximum Tolerated DoseMiddle AgedMolecular Targeted TherapyNeoplasm StagingNeoplasmsRetreatmentT-Lymphocyte SubsetsTreatment OutcomeTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAdvanced solid tumorsSolid tumorsTreatment-emergent adverse eventsPeripheral blood CD8Phase Ib studyTreatment-related discontinuationsDose-limiting toxicityCostimulatory receptor 4Event continual reassessment methodT cell costimulatory receptor 4Clin Cancer ResSupport further investigationBlood CD8Partial responseAdverse eventsDose escalationReceptor 4Clinical activityT cellsIb studyCombination treatmentContinual reassessment methodPatientsGrade 1Cancer ResOverall 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 trialsEndocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management
Sznol M, Postow MA, Davies MJ, Pavlick AC, Plimack ER, Shaheen M, Veloski C, Robert C. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treatment Reviews 2017, 58: 70-76. PMID: 28689073, DOI: 10.1016/j.ctrv.2017.06.002.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsCytotoxic T-lymphocyte antigen-4Checkpoint inhibitorsEndocrine eventsAdverse eventsTypes of irAEsEndocrine-related adverse eventsT-lymphocyte antigen-4Replacement of hormonesDeath receptor-1Target organ damageClose patient monitoringImmune checkpoint blockadeNon-specific symptomsAppropriate laboratory testingImmune checkpoint proteinsCheckpoint blockadeGrade 1/2Organ damageClinical benefitAdrenal glandAntigen-4Endocrine functionGastrointestinal tractResults 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 ResearchConceptsTreatment-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
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