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 ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedCarcinoma, Renal CellFemaleHumansKidney NeoplasmsNivolumabOvarian NeoplasmsTumor MicroenvironmentConceptsObjective 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 ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedB7-H1 AntigenCarcinoma, Transitional CellHumansLung NeoplasmsNeoplasmsUrinary Bladder NeoplasmsConceptsAdverse 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 carcinomaAutoimmune 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 ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAutoimmune DiseasesHumansImmunologic FactorsImmunotherapyIpilimumabMelanomaNivolumabRetinal DiseasesRetrospective StudiesSkin NeoplasmsConceptsAdvanced 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
Phase Ib Study of Atezolizumab Plus Interferon-α with or without Bevacizumab in Patients with Metastatic Renal Cell Carcinoma and Other Solid Tumors
Blank CU, Wong DJ, Ho TH, Bauer TM, Lee CB, Bene-Tchaleu F, Zhu J, Zhang X, Cha E, Sznol M. Phase Ib Study of Atezolizumab Plus Interferon-α with or without Bevacizumab in Patients with Metastatic Renal Cell Carcinoma and Other Solid Tumors. Current Oncology 2021, 28: 5466-5479. PMID: 34940094, PMCID: PMC8700717, DOI: 10.3390/curroncol28060455.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedBevacizumabCarcinoma, Renal CellHumansInterferon-alphaKidney NeoplasmsVascular Endothelial Growth Factor AConceptsRenal cell carcinomaObjective response ratePEG-interferon α-2aPhase Ib studyInterferon α-2bArm BSolid tumorsCell carcinomaClinical activityΑ-2aΑ-2bIb studyVascular endothelial growth factor inhibitorsFrequent treatment-related toxicitiesHigher objective response rateMetastatic renal cell carcinomaArm DTreatment-related toxicityPreliminary clinical activityGrowth factor inhibitorsMetastatic solid tumorsAcceptable tolerabilityFactor inhibitorsSafety profileCombination therapyEfficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial
Powles T, Atkins MB, Escudier B, Motzer RJ, Rini BI, Fong L, Joseph RW, Pal SK, Sznol M, Hainsworth J, Stadler WM, Hutson TE, Ravaud A, Bracarda S, Suarez C, Choueiri TK, Reeves J, Cohn A, Ding B, Leng N, Hashimoto K, Huseni M, Schiff C, McDermott DF. Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial. European Urology 2021, 79: 665-673. PMID: 33678522, PMCID: PMC9357270, DOI: 10.1016/j.eururo.2021.01.003.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Renal CellDisease ProgressionHumansKidney NeoplasmsSunitinibVascular Endothelial Growth Factor AConceptsMetastatic clear cell renal cancerProgression-free survivalObjective response rateSafety of atezolizumabSecond-line atezolizumabSecond-line treatmentSunitinib monotherapyDisease progressionSunitinib armRandomized phase 2 clinical trialMedian progression-free survivalTreatment-related adverse eventsMetastatic renal cell carcinomaPhase 2 clinical trialGrade 3/4 eventsInvestigator-assessed progressionImmune checkpoint inhibitorsPhase 2 studyKaplan-Meier methodAdvanced kidney cancerVascular endothelial growth factorClear cell renal cancerRenal cell carcinomaEndothelial growth factorAtezolizumab 1200
2020
Revisiting anti-CTLA-4 antibodies in combination with PD-1 blockade for cancer immunotherapy
Sznol M, Melero I. Revisiting anti-CTLA-4 antibodies in combination with PD-1 blockade for cancer immunotherapy. Annals Of Oncology 2020, 32: 295-297. PMID: 33307201, DOI: 10.1016/j.annonc.2020.11.018.Peer-Reviewed Original ResearchAntibodies, Monoclonal, HumanizedCarcinoma, Non-Small-Cell LungCTLA-4 AntigenHumansImmunotherapyLung NeoplasmsProgrammed Cell Death 1 ReceptorMogamulizumab 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 cancerBempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy
Sharma M, Khong H, Fa’ak F, Bentebibel SE, Janssen LME, Chesson BC, Creasy CA, Forget MA, Kahn LMS, Pazdrak B, Karki B, Hailemichael Y, Singh M, Vianden C, Vennam S, Bharadwaj U, Tweardy DJ, Haymaker C, Bernatchez C, Huang S, Rajapakshe K, Coarfa C, Hurwitz ME, Sznol M, Hwu P, Hoch U, Addepalli M, Charych DH, Zalevsky J, Diab A, Overwijk WW. Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy. Nature Communications 2020, 11: 661. PMID: 32005826, PMCID: PMC6994577, DOI: 10.1038/s41467-020-14471-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCarcinoma, Renal CellCD8-Positive T-LymphocytesCohort StudiesDrug Therapy, CombinationFemaleHumansInterferon-gammaInterleukin-2IpilimumabLymphocyte ActivationMelanomaMiceMice, Inbred C57BLPolyethylene GlycolsProdrugsReceptors, Interleukin-2T-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaConceptsNKTR-214Interleukin-2Treg depletionT cellsHigh-dose interleukin-2Suppressive regulatory T cellsSuperior anti-tumor activityAnti-tumor CD8Dose interleukin-2Peptide-based vaccinationRegulatory T cellsCheckpoint blockade therapyTreatment-associated toxicityIL-2 pathwayRenal cell carcinomaAnti-tumor activityAnti-cancer therapyMechanism of actionTreg dynamicsIntratumoral TregsBlockade therapyCytokines IFNCell carcinomaMetastatic melanomaTherapeutic impactAdenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer
Fong L, Hotson A, Powderly JD, Sznol M, Heist RS, Choueiri TK, George S, Hughes BGM, Hellmann MD, Shepard DR, Rini BI, Kummar S, Weise AM, Riese MJ, Markman B, Emens LA, Mahadevan D, Luke JJ, Laport G, Brody JD, Hernandez-Aya L, Bonomi P, Goldman JW, Berim L, Renouf DJ, Goodwin RA, Munneke B, Ho PY, Hsieh J, McCaffery I, Kwei L, Willingham SB, Miller RA. Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer. Cancer Discovery 2020, 10: 40-53. PMID: 31732494, PMCID: PMC6954326, DOI: 10.1158/2159-8290.cd-19-0980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellDrug Resistance, NeoplasmFemaleFollow-Up StudiesFuransHumansKidney NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisPyridinesPyrimidinesReceptor, Adenosine A2ASalvage TherapySurvival RateConceptsRenal cell cancerPretreatment tumor biopsiesClinical responseGene expression signaturesCell cancerTumor biopsiesPD-1/PD-L1 inhibitorsPD-1/PD-L1Refractory renal cell cancerPhase I clinical trialL1 combination therapyRecruitment of CD8Targetable immune checkpointsDurable clinical benefitPD-L1 inhibitorsT cell repertoireAdenosine 2A receptorAntitumor immunityReceptor blockadeImmune checkpointsPD-L1L1 antibodyClinical benefitCombination therapyImmune cells
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBrain NeoplasmsCohort StudiesFemaleHumansMaleMelanomaMiddle AgedSkin NeoplasmsConceptsBrain 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 progressionBullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy
Siegel J, Totonchy M, Damsky W, Berk-Krauss J, Castiglione F, Sznol M, Petrylak DP, Fischbach N, Goldberg SB, Decker RH, Stamatouli AM, Hafez N, Glusac EJ, Tomayko MM, Leventhal JS. Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. Journal Of The American Academy Of Dermatology 2018, 79: 1081-1088. PMID: 30025829, DOI: 10.1016/j.jaad.2018.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenDrug EruptionsFemaleHumansLichenoid EruptionsMaleMiddle AgedNeoplasm ProteinsNeoplasmsNivolumabPemphigoid, BullousProgrammed Cell Death 1 ReceptorRetrospective StudiesSkin Diseases, VesiculobullousTertiary Care CentersTreatment OutcomeConceptsPD-L1 therapyAnti-PD-1/PD-L1 therapyBullous disordersBullous eruptionPD-1/PD-L1 therapyCell death ligand-1 therapyAnti-programmed cell death 1Cancer therapyDeath ligand 1 therapySingle tertiary care centerLinear IgA bullous dermatosisYale-New Haven HospitalDistinct therapeutic challengesInterruption of immunotherapyPositive tumor responseSteroid-sparing agentTertiary care centerIgA bullous dermatosisCell death 1New Haven HospitalStable diseaseSystemic corticosteroidsSystemic steroidsMaintenance therapyL1 therapyClinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma
McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, Sznol M, Hainsworth J, Rathmell WK, Stadler WM, Hutson T, Gore ME, Ravaud A, Bracarda S, Suárez C, Danielli R, Gruenwald V, Choueiri TK, Nickles D, Jhunjhunwala S, Piault-Louis E, Thobhani A, Qiu J, Chen DS, Hegde PS, Schiff C, Fine GD, Powles T. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nature Medicine 2018, 24: 749-757. PMID: 29867230, PMCID: PMC6721896, DOI: 10.1038/s41591-018-0053-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Renal CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedMutationSunitinibTreatment OutcomeConceptsProgression-free survivalPFS hazard ratioRenal cell carcinomaHazard ratioPD-L1Cell carcinomaTreatment-naive metastatic renal-cell carcinomaRandomized phase 2 studyMetastatic renal cell carcinomaInflammatory gene expression signatureExploratory biomarker analysisPhase 2 studyImmune checkpoint blockadeCo-primary endpointsPrediction of outcomeAtezolizumab monotherapyCheckpoint blockadeGene expression signaturesNeoantigen burdenT effectorsClinical activityAtezolizumabBevacizumabTumor mutationsSunitinib
2017
Phase 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 ResEndocrine-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 ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsB7-H1 AntigenCTLA-4 AntigenEndocrine System DiseasesHumansIpilimumabNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorConceptsImmune-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 tractNuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Smithy JW, Moore LM, Pelekanou V, Rehman J, Gaule P, Wong PF, Neumeister VM, Sznol M, Kluger HM, Rimm DL. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2017, 5: 25. PMID: 28331615, PMCID: PMC5359951, DOI: 10.1186/s40425-017-0229-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, PharmacologicalDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon Regulatory Factor-1IpilimumabMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasms, Second PrimaryNivolumabProgrammed Cell Death 1 ReceptorConceptsProgression-free survivalObjective radiographic responsePD-L1 expressionPD-L1IRF-1 expressionMetastatic melanomaAnti-PD-1 therapyCombination ipilimumab/nivolumabHigh PD-L1 expressionAnti-PD-1 immunotherapyYale-New Haven HospitalIpilimumab/nivolumabPD-1 therapyPR/CRPre-treatment formalinRECIST v1.1 criteriaDeath ligand 1Valuable predictive biomarkerMajor unmet needNew Haven HospitalInterferon regulatory factor 1Combination ipilimumabProgressive diseaseRadiographic responseComplete response
2016
Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma
Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Cañamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, McDermott DF. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nature Communications 2016, 7: 12624. PMID: 27571927, PMCID: PMC5013615, DOI: 10.1038/ncomms12624.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBevacizumabCarcinoma, Renal CellCD8-Positive T-LymphocytesCell MovementDrug SynergismFemaleHumansKidneyKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedTreatment OutcomeVascular Endothelial Growth Factor AConceptsAntigen-specific T-cell migrationT cell migrationT cellsCombination treatmentAnti-tumor immune activationPD-L1 checkpoint inhibitionMetastatic renal cell carcinomaAddition of atezolizumabIntra-tumoral CD8Subset of patientsT cell infiltrationImmune cell activityRenal cell carcinomaEndothelial cell activationVariety of cancersLymphocytes increasesPeripheral CD8Checkpoint inhibitorsDurable responsesCheckpoint inhibitionImmune activationCell carcinomaVascular normalizationReceptor increasesCell activationPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortAtezolizumab, 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