2015
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
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 cohortA phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC).
Gettinger S, Brahmer J, Rizvi N, Ready N, Chow L, Antonia S, Buyse M, Jassem J, Finckenstein F, Crinò L, Lynch T. A phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2013, 31: tps8121-tps8121. DOI: 10.1200/jco.2013.31.15_suppl.tps8121.Peer-Reviewed Original ResearchNon-squamous NSCLCOverall survivalTyrosine kinase inhibitorsPD-L1Maintenance therapyAdvanced diseaseLung cancerDisease progressionPlatinum-based doublet chemotherapyRecurrent non-squamous NSCLCPhase III comparative studyMedian overall survivalObjective response ratePhase III studyProgression-free survivalPhase 1 studyCell lung cancerDurable antitumor activityPD-1 receptorImmune checkpoint receptorsT cell activationDoublet chemotherapyNSCLC ptsOS benefitUnacceptable toxicitySurvival and long-term follow-up of the phase I trial of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC).
Brahmer J, Horn L, Antonia S, Spigel D, Gandhi L, Sequist L, Sankar V, Ahlers C, Wigginton J, Kollia G, Gupta A, Gettinger S. Survival and long-term follow-up of the phase I trial of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2013, 31: 8030-8030. DOI: 10.1200/jco.2013.31.15_suppl.8030.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerPhase I trialOverall survivalMedian OSI trialCommon drug-related AEsDrug-related AEsMedian overall survivalPrior chemotherapy regimenAcceptable safety profilePhase 1 studyCell lung cancerPD-1 receptorImmune checkpoint receptorsDrug-related deathsT cell activationNSCLC ptsOS benefitChemotherapy regimenDose cohortsCheckpoint receptorsDeath-1Safety profileDiscontinuation criteria