2021
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
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
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
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab
Hamid O, Molinero L, Bolen CR, Sosman JA, Muñoz-Couselo E, Kluger HM, McDermott DF, Powderly J, Sarkar I, Ballinger M, Fassò M, O'Hear C, Chen DS, Hegde PS, Hodi FS. Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Clinical Cancer Research 2019, 25: 6061-6072. PMID: 31358540, DOI: 10.1158/1078-0432.ccr-18-3488.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorFatigueFemaleFeverFollow-Up StudiesHumansMaleMelanomaMiddle AgedPrognosisProgression-Free SurvivalPruritusRetrospective StudiesSeverity of Illness IndexSkinSkin NeoplasmsT-Lymphocytes, CytotoxicTranscriptomeYoung AdultConceptsTreatment-related adverse eventsAdverse eventsOverall survivalMetastatic melanomaCommon treatment-related adverse eventsMost treatment-related adverse eventsAntitumor T-cell activityMeaningful long-term survivalActivity of atezolizumabEfficacy-evaluable patientsPhase Ia studyTreatment-related deathsMedian overall survivalPD-L1 expressionProgression-free survivalCohort of patientsPhase I trialT cell activityOverall response rateBiological correlatesLong-term safetyLong-term survivalPrimary study objectiveDurable responsesGrade 1/2Treatment-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 analysisDurable 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
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 inhibitors
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
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Sznol M, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Atkins M, Kirkwood J, Burke M, Ralabate A, Rivera A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Krishnan S, Gupta A, Wolchok J. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). Journal Of Clinical Oncology 2014, 32: lba9003-lba9003. DOI: 10.1200/jco.2014.32.18_suppl.lba9003.Peer-Reviewed Original ResearchClinical activityTreatment-related adverse eventsMT statusManageable safety profilePrior systemic therapyPhase I trialMajority of ptsBRAF mutation statusBRAF MTIPI therapyStage M1cPrior therapyMedian durationObjective responseSystemic therapyAdvanced melanomaAdverse eventsConcurrent therapyI trialOS ratesSafety profileTumor reductionTumor responseGrade 3Wk 24