2020
Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer
Chiang AC, Sequist LVD, Gilbert J, Conkling P, Thompson D, Marcoux JP, Gettinger S, Kowanetz M, Molinero L, O'Hear C, Fassò M, Lam S, Gordon MS. Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Clinical Lung Cancer 2020, 21: 455-463.e4. PMID: 32586767, DOI: 10.1016/j.cllc.2020.05.008.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerRefractory small cell lung cancerImmune-related response criteriaTreatment-related adverse eventsProgression-free survivalOverall survivalLung cancerMedian investigator-assessed progression-free survivalGrade treatment-related adverse eventsInvestigator-assessed progression-free survivalTumor-specific T cell immunityMetastatic small cell lung cancerSolid Tumors version 1.1T-effector gene signaturePD-L1 mRNA expressionSafety of atezolizumabAntitumor activityMedian overall survivalResponse Evaluation CriteriaCohort of patientsPD-L1 signalingPhase 1 studyT cell immunityDuration of responseEligible patientsPhase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer
Hellmann MD, Gettinger S, Chow LQM, Gordon M, Awad MM, Cha E, Gong X, Zhou G, Walker C, Leopold L, Heist RS. Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer. International Journal Of Cancer 2020, 147: 1963-1969. PMID: 32141617, PMCID: PMC7496129, DOI: 10.1002/ijc.32951.Peer-Reviewed Original ResearchConceptsNonsmall cell lung cancerTreatment-related adverse eventsDose-limiting toxicityCell lung cancerAdverse eventsLung cancerStage IIIB/IV nonsmall cell lung cancerFatal treatment-related adverse eventsAdvanced nonsmall cell lung cancerCell death ligand 1Grade 3 dehydrationGrade 3 hyponatremiaGrade 3/4 eventsPhase 1 studyPlatinum-based chemotherapyDeath ligand 1Dose of treatmentAutoimmune encephalitisEligible patientsIntravenous atezolizumabStable diseasePrimary endpointPartial responsePrior linesIDO expression
2017
Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012.
Goldman J, Antonia S, Gettinger S, Borghaei H, Brahmer J, Ready N, Gerber D, Chow L, Juergens R, Shepherd F, Laurie S, Geese W, Li A, Li X, Hellmann M. Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012. Journal Of Clinical Oncology 2017, 35: 9093-9093. DOI: 10.1200/jco.2017.35.15_suppl.9093.Peer-Reviewed Original ResearchPD-L1 expressionComplete responsePD-L1Long-term OS benefitPD-L1 tumor expressionStage IIIB/IVTumor PD-L1 expressionChemotherapy-naive NSCLCECOG PS 0Experienced grade 3IIIB/IVManageable safety profileFirst-line treatmentPhase 1 studyLong-term survivorsLong-term outcomesMultiple tumor typesExploratory endpointsOS benefitAdvanced NSCLCPrimary endpointSecondary endpointsPS 0Unacceptable toxicityConsent withdrawal
2014
1054PD Nivolumab (Anti-Pd-1; Bms-936558, Ono-4538) in Combination with Platinum-Based Doublet Chemotherapy (Pt-Dc) or Erlotinib (Erl) in Advanced Non-Small Cell Lung Cancer (Nsclc)
Gettinger S, Rizvi N, Chow L, Borghaei H, Brahmer J, Juergens R, Shepherd F, Laurie S, Gerber D, Goldman J, Shen Y, Harbison C, Chen A, Antonia S. 1054PD Nivolumab (Anti-Pd-1; Bms-936558, Ono-4538) in Combination with Platinum-Based Doublet Chemotherapy (Pt-Dc) or Erlotinib (Erl) in Advanced Non-Small Cell Lung Cancer (Nsclc). Annals Of Oncology 2014, 25: iv363. DOI: 10.1093/annonc/mdu342.7.Peer-Reviewed Original ResearchObjective response rateBest overall responseProgression/unacceptable toxicityGrade 3Cisplatin 75Advanced NSCLCUnacceptable toxicityAdvanced non-small cell lung cancerDeath-1 immune checkpoint inhibitor antibodyChemotherapy-naïve NSCLC patientsImmune checkpoint inhibitor antibodyNon-small cell lung cancerProgression-free survival ratesRelated AEsCheckpoint inhibitor antibodyGenentech/RocheAcceptable safety profileDurable clinical benefitPhase 1 studyCell lung cancerAcceptable antitumor activityCarboplatin AUC6Doublet chemotherapyGemcitabine 1250Grade pneumonitis
2013
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).
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
2012
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.
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
2010
Phase 1 Study of Aflibercept Administered Subcutaneously to Patients with Advanced Solid Tumors
Tew WP, Gordon M, Murren J, Dupont J, Pezzulli S, Aghajanian C, Sabbatini P, Mendelson D, Schwartz L, Gettinger S, Psyrri A, Cedarbaum JM, Spriggs DR. Phase 1 Study of Aflibercept Administered Subcutaneously to Patients with Advanced Solid Tumors. Clinical Cancer Research 2010, 16: 358-366. PMID: 20028764, PMCID: PMC4211604, DOI: 10.1158/1078-0432.ccr-09-2103.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsDrug-related grade 3Vascular endothelial growth factor trapDose of afliberceptDose-escalation studyDose-proportional increaseInjection site reactionsPhase 1 studyManageable side effectsVascular endothelial growth factorWarrants further evaluationFavorable pharmacokinetic profileProgression of diseaseNovel antiangiogenic agentsEndothelial growth factorCommon toxicitiesStable diseasePulmonary embolismCerebral ischemiaSubcutaneous dosesSafety profileSingle doseSite reactionsSubcutaneous formulation