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, Couselo E, Rodríguez-Abreu D, Boni V, Schuchter L, Gonzalez-Cao M, Arance 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 cellsOutcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment
2022
FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy
Choueiri T, Kluger H, George S, Tykodi S, Kuzel T, Perets R, Nair S, Procopio G, Carducci M, Castonguay V, Folefac E, Lee C, Hotte S, Miller W, Saggi S, Lee C, Desilva H, Bhagavatheeswaran P, Motzer R, Escudier B. FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy. Journal For ImmunoTherapy Of Cancer 2022, 10: e005780. PMID: 36328377, PMCID: PMC9639138, DOI: 10.1136/jitc-2022-005780.Peer-Reviewed Original ResearchConceptsAdvanced renal cell carcinomaObjective response rateDuration of responseIO therapyImmuno-oncology therapiesRenal cell carcinomaOverall survivalCell carcinomaAnti-PD-1/PD-L1 therapyImmune-mediated adverse eventsMedian DORProgression-free survival ratesTreatment-related deathsManageable safety profileMedian overall survivalPD-L1 therapyDurable clinical benefitKarnofsky performance statusPrimary outcome measureHigh unmet needExploratory endpointsIpilimumab armPFS ratesStable diseaseAdverse eventsTumor mutational burden (TMB) in immune checkpoint inhibitor (ICI)-naïve and -experienced patients with metastatic melanoma treated with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy.
Kluger H, Sarnaik A, Chesney J, Lewis K, Weber J, Gogas H, In G, Terheyden P, Lee S, Jagasia M, Masteller E, Qi R, Gontcharova V, Shi W, Fiaz R, Sulur G, Wu R, Chen G, Thomas S. Tumor mutational burden (TMB) in immune checkpoint inhibitor (ICI)-naïve and -experienced patients with metastatic melanoma treated with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy. Journal Of Clinical Oncology 2022, 40: 9524-9524. DOI: 10.1200/jco.2022.40.16_suppl.9524.Peer-Reviewed Original ResearchHigh tumor mutational burdenObjective response rateTumor mutational burdenCase-control studyAdvanced melanomaMetastatic melanomaTumor harvestResponse rateCell therapyT cell receptor repertoireLymphocyte cell therapyTumor microenvironment profilesImmune checkpoint inhibitorsPercentage of patientsTreatment of patientsHigh TMB groupMut/MbLogistic regression analysisICI exposureICI therapyRECIST v1.1Checkpoint inhibitorsStudy entryTMB groupBRAF statusImmune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function
Jessel S, Weiss SA, Austin M, Mahajan A, Etts K, Zhang L, Aizenbud L, Perdigoto AL, Hurwitz M, Sznol M, Herold KC, Kluger HM. Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function. Frontiers In Oncology 2022, 12: 836859. PMID: 35350573, PMCID: PMC8958012, DOI: 10.3389/fonc.2022.836859.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaCombination immune checkpoint inhibitorsCell carcinomaClinical experienceSelect casesIncidence of hypophysitisInstitution's clinical experienceYale Cancer CenterObjective response rateAdrenal axis hormonesFree testosterone levelsMerkel cell carcinomaHigh rateMultiple tumor typesCheckpoint inhibitorsPituitary axesReal-world practiceFree testosteroneMedian timeMelanoma patientsOverall incidencePituitary functionTreatment delayAxis hormones
2021
Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Larkin J, Sarnaik A, Chesney J, Khushalani N, Kirkwood J, Weber J, Lewis K, Medina T, Kluger H, Thomas S, Domingo-Musibay E, Olah J, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Shi W, Wu R, Fardis M, Hamid O. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. Journal Of Clinical Oncology 2021, 39: 9505-9505. DOI: 10.1200/jco.2021.39.15_suppl.9505.Peer-Reviewed Original ResearchAnti-PD-1 therapyPrior anti-PD-1 therapyObjective response rateImmune checkpoint inhibitorsAdvanced melanomaPrimary resistanceAnti-PD-1 resistanceAnti-PD-1 responseBaseline tumor burdenDays of cyclophosphamideDays of fludarabineMedian cumulative durationMedian prior linesLong-term followAdoptive cell therapyStandard of careDetection of progressionNew safety risksDuration of exposureAutologous tumorMelanoma progressPrior therapyRECIST 1.1TIL productionCheckpoint inhibitorsLifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2656-2666. PMID: 33979178, PMCID: PMC8376325, DOI: 10.1200/jco.21.00612.Peer-Reviewed Original ResearchConceptsObjective response rateDisease control rateAdvanced melanomaPrimary refractoryControl rateMetastatic melanomaTreatment optionsInterleukin-2Investigator-assessed objective response rateHigh-dose interleukin-2Tumor-Infiltrating Lymphocyte TherapyImmune checkpoint inhibitorsPrimary end pointTumor-infiltrating lymphocytesEffective treatment optionLimited treatment optionsAdoptive cell therapyMajor unmet needLymphodepletion regimenPrior therapyCheckpoint inhibitorsAdverse eventsDurable responsesMedian durationPartial response
2020
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Diab A, Tannir NM, Bentebibel SE, Hwu P, Papadimitrakopoulou V, Haymaker C, Kluger HM, Gettinger SN, Sznol M, Tykodi SS, Curti BD, Tagliaferri MA, Zalevsky J, Hannah AL, Hoch U, Aung S, Fanton C, Rizwan A, Iacucci E, Liao Y, Bernatchez C, Hurwitz ME, Cho DC. Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery 2020, 10: 1158-1173. PMID: 32439653, DOI: 10.1158/2159-8290.cd-19-1510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsImmunotherapyInterleukin-2Kidney NeoplasmsLung NeoplasmsLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNivolumabPolyethylene GlycolsProgrammed Cell Death 1 ReceptorTreatment OutcomeYoung AdultConceptsTreatment-related adverse eventsAdvanced solid tumorsPD-L1 statusSolid tumorsGrade 3/4 treatment-related adverse eventsPD-1/PD-L1 blockadeCommon treatment-related adverse eventsPhase I dose-escalation trialPoor prognostic risk factorsTotal objective response rateI dose-escalation studyI dose-escalation trialLongitudinal tumor biopsiesPD-L1 blockadeT-cell enhancementTreatment-related deathsObjective response ratePhase II doseDose-escalation studyDose-escalation trialDose-limiting toxicityFlu-like symptomsPrognostic risk factorsTumor-infiltrating lymphocytesCytotoxicity of CD8FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).
Choueiri T, Kluger H, George S, Tykodi S, Kuzel T, Perets R, Nair S, Procopio G, Carducci M, Castonguay V, Folefac E, Lee C, Hotte S, Miller W, Saggi S, Gold D, Motzer R, Escudier B. FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC). Journal Of Clinical Oncology 2020, 38: 5007-5007. DOI: 10.1200/jco.2020.38.15_suppl.5007.Peer-Reviewed Original ResearchAdvanced renal cell carcinomaDuration of responseTreatment-related adverse eventsAdverse eventsPartial responsePrior linesGrade treatment-related adverse eventsImmune-mediated adverse eventsProgression-free survival probabilityDurable partial responseTreatment-related deathsCheckpoint inhibitor therapyObjective response rateCheckpoint inhibitor treatmentRenal cell carcinomaCombination nivolumabInvestigational combinationPrior TKICheckpoint inhibitorsPrimary endpointWeek 24Complete responseInhibitor therapyTKI therapyPrior progression
2019
Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. Journal Of Clinical Oncology 2019, 37: jco.18.01896. PMID: 30726175, PMCID: PMC6424137, DOI: 10.1200/jco.18.01896.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Merkel CellFemaleFollow-Up StudiesHumansHypothyroidismMaleMiddle AgedPneumoniaProgression-Free SurvivalRemission InductionResponse Evaluation Criteria in Solid TumorsSkin NeoplasmsConceptsObjective response rateProgression-free survivalMerkel cell carcinomaAdvanced MCCAnti-programmed cell death-1 therapyCell death-1 pathway inhibitorsGreater treatment-related adverse eventsDeath-1 pathway inhibitorsMulticenter phase II trialTreatment-related adverse eventsAdvanced Merkel cell carcinomaDurable tumor controlManageable safety profileMedian OS timeMedian response durationSolid Tumors v1.1Treatment-related deathsTumor viral statusDate of patientsFirst-line chemotherapyFirst-line therapyMedian PFS timePhase II trialResponse Evaluation CriteriaOverall survival data
2018
Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma
Hellerstedt BA, Vogelzang NJ, Kluger HM, Yasenchak CA, Aftab DT, Ramies DA, Gordon MS, Lara P. Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non–small-cell Lung Carcinoma. Clinical Lung Cancer 2018, 20: 74-81.e1. PMID: 30528315, DOI: 10.1016/j.cllc.2018.10.006.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMedian progression-free survivalCell lung carcinomaWeek 12Adverse eventsDiscontinuation trialLung carcinomaTreatment-related grade 5 adverse eventsCommon grade 3/4 adverse eventsBioavailable tyrosine kinase inhibitorGrade 3/4 adverse eventsGrade 5 adverse eventsOverall disease control rateSolid Tumors version 1.0Epidermal growth factor receptor (EGFR) mutationsOpen-label leadPhase II PlaceboRandomized discontinuation trialDisease control ratePalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaGrowth factor receptor 2Vascular endothelial growth factor receptor 2Endothelial growth factor receptor 2
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 cohortEfficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States
Gangadhar TC, Hwu WJ, Postow MA, Hamid O, Daud A, Dronca R, Joseph R, O’Day S, Hodi FS, Pavlick AC, Kluger H, Oxborough RP, Yang A, Gazdoiu M, Kush DA, Ebbinghaus S, Salama AKS. Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States. Journal Of Immunotherapy 2017, 40: 334-340. PMID: 29028788, PMCID: PMC5647109, DOI: 10.1097/cji.0000000000000186.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsClinical Trials as TopicDrug Resistance, NeoplasmDrug-Related Side Effects and Adverse ReactionsExanthemaFatigueFemaleHumansMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasm StagingTreatment OutcomeUnited StatesYoung AdultConceptsTreatment-related adverse eventsAdverse eventsAdvanced melanomaGrade 3/4 treatment-related adverse eventsNational Cancer Institute Common Terminology CriteriaUnresectable stage III/IV melanomaStage III/IV melanomaImmune-related response criteriaDeath-1 antibodySafety of pembrolizumabTreatment-related deathsUse of pembrolizumabCommon Terminology CriteriaObjective response rateSubcutaneous tissue disordersAccess programEvaluable patientsTerminology CriteriaCare therapyComplete responseInvestigator reviewGastrointestinal disordersDisease progressionTissue disordersBRAF inhibitorsPhase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma
Daud A, Kluger HM, Kurzrock R, Schimmoller F, Weitzman AL, Samuel TA, Moussa AH, Gordon MS, Shapiro GI. Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma. British Journal Of Cancer 2017, 116: 432-440. PMID: 28103611, PMCID: PMC5318966, DOI: 10.1038/bjc.2016.419.Peer-Reviewed Original ResearchConceptsObjective response rateStable diseaseWeek 12Metastatic melanomaEvaluable patientsDiscontinuation trialUveal melanomaCommon grade 3/4 adverse eventsGrade 3/4 adverse eventsTreatment-related deathsMedian overall survivalProgression-free survivalResponse Evaluation CriteriaCohort of patientsStudy days 1Further clinical investigationPhase IIAbdominal painDiverticular perforationPrimary endpointAdverse eventsOverall survivalTarget lesionsClinical activityClinical investigation
2016
PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. New England Journal Of Medicine 2016, 374: 2542-2552. PMID: 27093365, PMCID: PMC4927341, DOI: 10.1056/nejmoa1603702.Peer-Reviewed Original ResearchConceptsAdvanced Merkel cell carcinomaMerkel cell carcinomaObjective response rateVirus-positive tumorsVirus-negative tumorsResponse rateDrug-related grade 3MCPyV-specific T cellsDose of pembrolizumabImmune inhibitory pathwaysPrevious systemic therapyTumor viral statusPD-1 blockadePrimary end pointFirst-line therapyProgression-free survivalResponse Evaluation CriteriaAggressive skin cancerMCPyV-positive tumorsMerkel cell polyomavirusAdverse eventsPartial responseSystemic therapyComplete responsePD-1
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 ResearchConceptsMaximum-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
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 dosesSafety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL).
Wolchok J, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Reed K, Burke M, Caldwell A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Horak C, Korman A, Wigginton J, Gupta A, Sznol M. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). Journal Of Clinical Oncology 2013, 31: 9012-9012. DOI: 10.1200/jco.2013.31.15_suppl.9012.Peer-Reviewed Original ResearchObjective response rateRelated adverse eventsPhase III trialsConcurrent therapyIII trialsPD-1Clinical activityCTLA-4/PDIpilimumab combination therapyCTLA-4 blockadeManageable safety profilePhase 1 studyPhase I trialImmune checkpoint receptorsIpilimumab therapyMonotherapy dataPrior therapySymptom resolutionAdverse eventsI trialAdvanced melanomaDurable CRCheckpoint receptorsSafety profileCombination therapyClinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM).
Hamid O, Sosman J, Lawrence D, Sullivan R, Ibrahim N, Kluger H, Boasberg P, Flaherty K, Hwu P, Ballinger M, Mokatrin A, Kowanetz M, Chen D, Hodi F. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). Journal Of Clinical Oncology 2013, 31: 9010-9010. DOI: 10.1200/jco.2013.31.15_suppl.9010.Peer-Reviewed Original ResearchObjective response rateMM ptsPD-L1Tumor shrinkageAntitumor activityImmunotherapy-responsive diseasePD-L1 overexpressionTreatment-related deathsPD-L1 statusPD-L1 antibodiesHuman monoclonal antibodyInitial antitumor activityPt ageRECIST responseRECIST v1.1Median durationPrior surgeryPS 0Radiographic progressionSystemic therapyElevated ASTPD-1Dose escalationHistologic subtypeInitial treatment
2008
Toxicity 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 number