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 CD8Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer
Bar N, Costa F, Das R, Duffy A, Samur M, McCachren S, Gettinger S, Neparidze N, Parker TL, Bailur JK, Pendleton K, Bajpai R, Zhang L, Xu ML, Anderson T, Giuliani N, Nooka A, Cho HJ, Raval A, Shanmugam M, Dhodapkar KM, Dhodapkar M. Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer. JCI Insight 2020, 5 PMID: 32427579, PMCID: PMC7406262, DOI: 10.1172/jci.insight.129353.Peer-Reviewed Original ResearchConceptsPD-L1 blockadePD-1 blockadeAsymptomatic multiple myelomaMonocyte-derived DCsPD-L1Immunologic effectsT cellsMyeloid cellsAntigen-specific T cell expansionAnti-PD-1 therapyMyeloid antigen-presenting cellsDistinct inflammatory signatureSystemic immunologic effectsLung cancer patientsT cell expansionAntigen-presenting cellsMyeloid activationMyeloid inflammationInflammatory signatureNIH/NCICheckpoint blockadeDC maturationL1 therapyCombination therapyInflammatory phenotype
2014
1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A
Soria J, Gettinger S, Gordon M, Heist R, Horn L, Spigel D, Kowanetz M, Mokatrin A, Xiao Y, Sandler A, Felip E. 1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A. Annals Of Oncology 2014, 25: iv465. DOI: 10.1093/annonc/mdu349.101.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1 blockadeIHC 2PD-L1Immune cellsNSCLC ptsB7-H4B7-H3PD-L2Tumor cellsIHC 0Clinical activityNon-small cell lung cancer patientsTumor-infiltrating immune cellsCell lung cancer patientsEmployees of GenentechReceptor PD-1Tumor immune microenvironmentLung cancer patientsPD-L1 IHCPD-L1 bindingRoche/GenentechImmune-related genesBristol-Myers SquibbPFS rates
2013
Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study.
Powderly J, Koeppen H, Hodi F, Sosman J, Gettinger S, Desai R, Tabernero J, Soria J, Hamid O, Fine G, Xiao Y, Mokatrin A, Wu J, Anderson M, Irving B, Chen D, Kowanetz M. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. Journal Of Clinical Oncology 2013, 31: 3001-3001. DOI: 10.1200/jco.2013.31.15_suppl.3001.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1Blood-based biomarkersPD-1T cellsPD-L1 tumor expressionTumor samplesT-cell gene signaturePD-L1 blockadeT cell infiltrationMetastatic solid tumorsPD-L1 upregulationT cell reactivationT cell subsetsImmune cell subsetsTumor immune microenvironmentPretreatment tumor samplesAvailable tumor tissueHuman monoclonal antibodyActivated T cellsT cell activationTumor CD8Expansion cohortAntitumor immunityBiopsy cohort