453P Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Solid Tumors: Clinical Activity, Safety, and Molecular Markers
Topalian S, Brahmer J, Hodi F, McDermott D, Smith D, Gettinger S, Taube J, Gupta A, Wigginton J, Sznol M. 453P Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Solid Tumors: Clinical Activity, Safety, and Molecular Markers. Annals Of Oncology 2012, 23: ix157. DOI: 10.1016/s0923-7534(20)33011-8.Peer-Reviewed Original ResearchBristol-Myers SquibbBMS-936558Objective responseAnti-PD-1 monoclonal antibodyAdditional long-term followAnti-programmed death-1PD-L1 expression statusProgression-free survival ratesNon-small cell lungDrug-related AEsObjective response rateAdvanced solid tumorsCo-inhibitory receptorsPretreatment tumor biopsiesPD-1 ligandsLong-term followOverall tumor burdenFurther clinical developmentPredictive molecular markersActivated T cellsCohort expansionRECIST v1.0Stable diseaseAdvanced NSCLCUnacceptable toxicity1237PD Clinical Activity and Safety of Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Non-Small Cell Lung Cancer (NSCLC)
Gettinger S, Horn L, Antonia S, Spigel D, Gandhi L, Sequist L, Wigginton J, Kollia G, Gupta A, Brahmer J. 1237PD Clinical Activity and Safety of Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Non-Small Cell Lung Cancer (NSCLC). Annals Of Oncology 2012, 23: ix405. DOI: 10.1016/s0923-7534(20)33809-6.Peer-Reviewed Original ResearchAdvanced non-small cell lung cancerNon-small cell lung cancerBristol-Myers SquibbBMS-936558NSCLC ptsStable diseasePartial responseClinical activitySquamous non-small cell lung cancerAdditional long-term followCommon drug-related AEsDrug-related AEsECOG performance statusObjective response rateCo-inhibitory receptorsLong-term followCell lung cancerCycles of treatmentDrug-related deathsHuman monoclonal antibodyActivated T cellsCohort expansionEvaluable ptsPrior therapyRECIST v1.0Anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced solid tumors: Clinical activity, safety, and a potential biomarker for response.
Topalian S, Brahmer J, Hodi F, McDermott D, Smith D, Gettinger S, Taube J, Drake C, Pardoll D, Antonia S, Spigel D, Atkins M, Lawrence D, McDonald D, Jure-Kunkel M, Korman A, Kollia G, Gupta A, Wigginton J, Sznol M. Anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced solid tumors: Clinical activity, safety, and a potential biomarker for response. Journal Of Clinical Oncology 2012, 30: cra2509-cra2509. DOI: 10.1200/jco.2012.30.18_suppl.cra2509.Peer-Reviewed Original ResearchPD-1/PD-L1 pathwayPD-L1 pathwayPotential predictive biomarkersBMS-936558Predictive biomarkersNon-small cell lung cancerPre-treatment tumor biopsiesCastrate-resistant prostate cancerCo-inhibitory receptorsPD-L1 expressionPD-1 ligandsCell lung cancerOverall tumor burdenActivated T cellsCohort expansionEvaluable ptsRECIST 1.0Advanced NSCLCMedian durationDeath-1PD-1PD-L1Therapy cyclesNew lesionsTumor burdenSafety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New England Journal Of Medicine 2012, 366: 2443-2454. PMID: 22658127, PMCID: PMC3544539, DOI: 10.1056/nejmoa1200690.Peer-Reviewed Original ResearchConceptsAnti-PD-1 antibodyCell lung cancerRenal cell cancerObjective responseLung cancerAdverse eventsPD-L1Drug-related adverse eventsPD-1 ligand expressionCastration-resistant prostate cancerImmune-related causesPretreatment tumor specimensAdverse event profilePD-L1 expressionPD-1-PDCumulative response rateBMS-936558Immune correlatesL1 pathwayAdvanced melanomaComplete responseDeath-1PD-1Negative tumorsPositive tumorsClinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).
Brahmer J, Horn L, Antonia S, Spigel D, Gandhi L, Sequist L, Wigginton J, McDonald D, Kollia G, Gupta A, Gettinger S. Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2012, 30: 7509-7509. DOI: 10.1200/jco.2012.30.15_suppl.7509.Peer-Reviewed Original ResearchBMS-936558Advanced NSCLCClinical activityPrior tyrosine kinase inhibitorsPrior chemotherapy regimenECOG performance statusCo-inhibitory receptorsPlatinum-based chemotherapyCell lung cancerOverall tumor burdenCycles of treatmentPercent of ptsDrug-related deathsTyrosine kinase inhibitorsActivated T cellsCohort expansionNSCLC ptsPrior therapyRECIST 1.0Chemotherapy regimenMedian durationMetastatic diseaseMultiple histologiesPerformance statusLymph nodesA phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer.
Gettinger S, Rizvi N, Shepherd F, Chow L, Laurie S, Spigel D, Sbar E, Shen Y, Brahmer J. A phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer. Journal Of Clinical Oncology 2012, 30: tps2615-tps2615. DOI: 10.1200/jco.2012.30.15_suppl.tps2615.Peer-Reviewed Original ResearchBMS-936558Cell lung cancerAdverse eventsTreatment armsLung cancerDisease progressionAnti-PD-1 monoclonal antibodyStage IIIB/IV NSCLCPlatinum-based doublet chemotherapyStage IIIB/IVImpressive tumor responsesCarboplatin/paclitaxelDisease control rateIIIB/IVFirst-line standardPD-1 expressionSerious adverse eventsDose-limiting toxicityGemcitabine/cisplatinPhase 1 studyPlatinum-based chemotherapyPhase 1 trialCancer-related mortalityOverall response rateWithdrawal of consent