晚期NSCLC免疫一线治疗策略PPT格式课件下载.pptx

晚期NSCLC免疫一线治疗策略PPT格式课件下载.pptx

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,20vHsR.12.2个,TC3或IC3,W20T.2：

vs.13.1个,月HR,P0=.509.0106,月HR0.65P=0.00110.3vs.6.0,OSPFS（月）ORR（%）,45vs.28,月P0=.609.0037.1vs.6.4（TPS50%）40vs.32（TPS50%）,TPS50%118（76.6）vs.135（90.0）48（31.2）vs.80（53.3）20（13.2）vs.1（0.7）,8.1vs.5.0（TC3或IC3）38.3vs.28.6（TC3或IC3）173（60.5）vs.224（85.2）37（12.9）vs.116（44.1）19（6.6）vs4（1.5）*,不良事件n（%）,任意级别TRAE3级TRAE3级irAE,399（63）vs.,151533（179.08）vs.252（41）51（8.0%）vs.9（1.5）,NSCLC一线免疫单药研究,用药方案,帕博利珠单抗vs.含铂双药,ABCPvsACPvs,BCP,Nivolumab3mg/kgQ2W+,Ipilimumab1mg/kgQ6W（）,4cycles,（4cycles）,moQ3W,ITT-WT:

19.5vs14.7vs.Che,Nivolumab360mgQ3W+,Ipilimumab1mg,vs.CheQm6oWQ（3W2cy（cl4e）cycles）,P0.01HR0.80,TWCT1/:

2/3或IC1/2/34-vs,1622.5vs.24.,TC0和IC0-WT:

14.8v16s.9.vs.14.1,OS,HRP0.0,ITT：

22vs.10.7个月PD,0.56%:

NR1,10.1,PDL115-409%:

21.18v2s.v1s,PDL11%17.2vs10.2,HRP0.007,PDL11%17.1vs.14.9,PD0.7917.2vs.12.2,L11%HR0.62,HR,ITT人群15.6vs.10.9,0.66,PD15.8vs10.9HR0.64,L11%,PD16.8vs9.8HR0.62,NSQL1171v%s.11.9,HR0.69SQ14.5vs.9.1HR0.62,PFS,9.0vs4.9,8.3vs6.8,5.1vs.5.6,NSCLC一线免疫联合用药研究,1）GhandiL,etal.NEJM.16April2018.2）GadgeelS,etal.PresentedatASCO2019.Abstract9013.3）Rodriguez-AbreuD.PresentedatASCO2020.Abstract9582.4）Paz-AresL,etal.PresentedatASCO2018.Abstract105.5）Paz-Ares,etal.NEnglJMed2018;

379:

2040-2051.6）Paz-AresL,etal.PresentedatESMO2019.AbstractLBA82.7）PetersS,etal.PresentedatESMO2019.AbstractLBA4.8）HellmanMet,al.NEJM.28Sept2019.9）RamalingamS,etal.PresentedatASCO2020.Abstract9500.10）ReckM,etal.PresentedatASCO2020.Abstract9501.,一线非小细胞肺癌主要临床研究数据比较（2020ASCO摘要公布）,IMpower150:

Phase3studyofACPorABCPvsBCPinchemotherapy-naivepatientswithmetastaticnon-squamousNSCLC,FedericoCappuzzo.2020ASCOAbstract9587.,Co-primaryendpoints:

PFSintheITT-WTpopulationPFSintheTeff-highWTpopulationOSintheWTpopulation.,PFSandPSintheITTpopulationIndependentreviewfacilityassessedPFSintheWTpopulationInvestigator-assessedPFSinthePD-L1expressionsubgroupsintheWTpopulationORRandDORintheWTpopulationSafetyintheITTpopulation,Atezolizumab+carboplatinc+paclitaxel（ACP）4or6cycles,Atezolizumab+bevacizumab+carboplatinpacl+itaxel（ABCP）,Atezolizumab,Maintenancetherapy（nocrossoverpermitted）,Bevacizumab+carboplatin+paclitaxel（BCP）4or6cyclesKeysecondaryendpoints,Atezolizumabb+evacizumab,Bevacizumab,TreatedwithatezolizumabuntilPDperRECIST1.1orlossofclinicalbenefitand/orTreatedwithbevacizumabuntilPDperRECIST1.1,Survivalup,StageIVorrecurrentmetastaticnon-squamousNSCLCChemotherapynaiveTumortissueforbioamvarilkaebrletestingAnyPD-L1IHCstatusStratificationfactors:

SexPD-L1IHCexpressionLivermetastasesN=1202,R,1:

1:

1,IMpower150demonstratedstatisticallysignificantandcmlienaicnainllgyfulimprovementswithABCPvsBCPinPFSandOS,SocinskiMA,etal.NEnglJMed.2018Jun14;

378（24）2288-2301.,Investigator-AssessedPFSintheWTPopulation,OSintheWTPopulation,IMpower150:

ExploratoryAnalysisofBrainMetastasesDevelopment,Thebevacizumab-containingarmsofABCPandBCPhadcomparable,lowerratesofnewbrainlesiondevelopmentonstudyAtrendtowarddelayeddevelopmentofnewbrainlesionswasobservedwithABCPNonewsafetysignalswereobservedinthisexploratoryanalysisRateofNewBrainLesionsintheITTPopulationTTDofNewBrainLesionsintheITTPopulation,Thisreportfocusesonexploratoryanalyses,includingrateandtimetodevelopment（TTD）ofnewbrainmetastasesintheITTpopulation,regardlessofthepresenceofbrainmetastasesatbaseline,aswellassafetyinpatientswithandwithoutbrainmetastasesFedericoCappuzzo.2020ASCOAbstract9587.,HR=0.68,11.90%,7.00%,18%16%14%12%,IMpower150:

Exploratoryefficacyanalysisinpatientswithbulkydisease*,ExploratoryefficacyanalysesincludedPFS,OS,ORR,timetoresponse（TTR）inthesesubgroups;

safetywasalsoassessed.OutcomesarereportedforpatientsenrolledintheABCPvsBCP,arms.,*patientswithhightumorburdenorlargesizeRobertJotte.2020ASCO,Withaminimumfollow-upof32.4moths（datacutoff:

Sep13,2019）,ABCPshowedimprovedOS,PFSandORRvsBCPinpatientswithhighandlowdiseaseburden.HighdiseaseburdendidnotimpactTTR.ThesafetyprofileofABCPwascomparablebetweenITT-WT（noEGFRorALKalterations）patientsandhighdiseaseburdensubgroups.,CheckMate227Part1:

Three-yearupdateofPhase3studyofNivolumab+ipilimumabin1LNSCLC,Databaselock:

February28,2020;

minimum/medianfollow-upforOS:

37.7months/43.1months.Treatmentwascontinueduntildiseaseprogression,unacceptabletoxicity,orfor2yearsforimmunotherapy;

aNCT02477826;

bNIVO（3mg/kgQ2W）+IPI（1mg/kgQ6W）;

CNSQ:

pemetrexed+cisplatinorcarboplatin,Q3Wfor4cycles,withoptionalpemetrexedmaintenancefollowingchemoorNIVO+pemetrexedmaintenancefollowingNIVO+chemo;

SQ:

gemcitabine+cisplatin,orgemcitabine+carboplatin,Q3Wfor4cycles;

dNlVO（240mgQ2W）;

eNIVO（360mgQ3W）;

fBothendpointsweremet;

resultswerepreviouslyreported.,Part1aPD-L1expression1%,Part1bPD-L1expression1%,N=550,N=1189,NIVO+IPIbn=396,Chemocn=397NIVOdn=396,NIVO+IPIbn=187,Chemocn=186NIVOe+chemocn=177,Independentpenridmpaoriynts:

NIVO+IPIvschemofPFSinhighTMB（10mut/Mb）populationOSinPD-L11%population,R,1:

1,1:

1R,KeyEligibilityCriteriaStageIVorrecurrentNSCLCNopriorsystemictherapyNosensitizingEGFRmutationsorknownALKalterationsNountreatedCNSmetastasesECOGPS0-1StratifiedbySQvsNSQ,SureshS.Ramalingam.2020ASCOAbstract9500.,First-lineNIVO+IPIcontinuedtoprovidelong-termOSbenefitsregardlessofPD-L1expression,Databaselock:

minimumfollow-upforOS:

37.7months,PD-L11%,PD-L11%,SureshS.Ramalingam.2020ASCOAbstract9500.,First-lineNIVO+IPIcontinuedtoprovidelong-termPFSbenefitsregardlessofPD-L1expression,SureshS.Ramalingam.2020ASCOAbstract9500.,3-yearupdate:

ORRandDORamongpatientswithPD-L11%or1%,SureshS.Ramalingam.2020ASCOAbstract9500.,CheckMate9LA:

Phase3studyofNivolumab+ipilimumab+2cyclesofplatinum-doubletchemotherapyvs4cycleschemotherapyin1LNSCLC,SecondaryendpointsPFSbyBICRORRbyBICREfficacybytumorPD-L1expression,NIVO360mgQ3W+IPI1mg/kgQ6W+ChemoQ3W（2cycles）,ChemoQ3W（4cycles）Withoptionalpemetrexedmai（nNteSnQa）nce,Untildiseaseprogression,unacceptabletoxicity,orfor2yearsforimmunotherapy,KeyEligibilityCriteriaStageIVorrecurrentNSCLCNopriorsystemictherapyNosensitizingEGFRmutationsorknownALKalterationsECOGPS0-1StratifiedbyPD-L1b（1%cvs1%）,Sex,andhistology（SQvsNSQ）,R1:

1,MartinReck.Rudin.2020ASCOAbstract9501.,n=361,n=358PrimaryendpointOS,n=719,NIVO+IPI+chemosignificantlyprolongedOScomparedvschemo,PrimaryEndpoint:

OSatinterimanalysis,PrimaryEndpoint（updated）:

OS,Minimumfollow-up:

8.1mothsforOS;

6.5monthsforPFS/ORR,Minimumfollow-up:

12.7moths,MartinReck.Rudin.2020ASCOAbstract9501.,Atapreplannedinterimanalysis,OSwassignificantlyprolongedwithNIVO+IPI+chemovschemo;

statisticallysignificantimprovementsinPFSandORRwereseen.Withlongerfollow-up,NIVO+IPI+chemovschemocontinuedtoprovidelongerOS,Overallsurvivalbyhistology,TheclinicalbenefitwithNIVO+IPI+chemowasconsistentacrosshistologies,MartinReck.Rudin.2020ASCOAbstract9501.,TheclinicalbenefitwithNIVO+IPI+chemowasconsistentacrossallPD-L1expressionlevels,OverallsurvivalbyPD-L1expressionlevel,MartinReck.Rudin.2020ASCOAbstract9501.,Safetysummary,TRAEstypicallyassociatedwithchemo,Treatment-relatedselectAEswithNIVO+IPI+chemoa,b,Median（range）durationoftherapywas6.1（0-23.5）monthsand2.4（0-24.0）monthsforNIVO+IPI+chemoversuschemo,respectivelyMostcommonany-gradeTRAEs（15%）werenausea,anemia,astheniaanddiarrhea,MartinReck.Rudin.2020ASCOAbstract9501.,Thinkabouttherelationshipbetweenthedosageofimmunotherapyanditsefficacyandsafety?

CheckMate227vs.CheckMate9LA,WhataboutfutureforadvancedNSCLC?

背景：

TIGIT,通,路,背景：

TIGIT通路,TIGIT（具有Ig和ITIM结构域的T细胞免疫受体）是一种在多种免,疫,细胞（包括T细胞和NK细胞1-3）上表达的新型抑制受体,抑制,TIGIT通过与肿,瘤细胞和抗原呈递细胞（APC）上的配体PVR结合来,T细胞和NK细胞,中,TIGIT表达与PD-1表达密切相关，尤其是在肺癌的肿瘤浸润性T细胞,假设：

防止TIGIT与其配体结合的抗TIGIT抗体可以恢复抗肿瘤反,应,，并可以补充抗PD-L1/PD-1抗体的活性,N1KM，自然杀伤细胞；

PVR，脊髓灰质炎病毒受体200a9nierietal.TrendsImmunology2017;

2Rotteetal.AnnalsofOncology2018;

3Yuetal.NatureImmunology,图片改编自Manierietal.,TrendsImmunology,2017,肿瘤细胞/,AP,C,T细胞/,NK细,胞,背景：

抗TIGIT抗体,Tiragolumab是全T人ir源agIgoGlu1/mkaappba抗TIGIT临床前模型显示，抗TIGIT抗体+抗PD-单克隆抗体，其完整的Fc区域可以阻止L1抗体联合治疗能够协同改善小鼠的肿TIGIT与其受体PVR结合瘤控制并延长生存期。

BAanctikbgordoyund:

Tiragolumab,anAnti-TIGIT,肿瘤细胞,/APC,阿替利珠单抗,T细胞/,NK细胞,图片改编自Manierietal.T20re17ndsImmunology,同种型,抗PD-L1抗TIGIT,抗PD-L1+,抗TIGIT完全缓解（CR）日,CITYSCAPE:

StudyDesignTiragolumab600mgIVq3w,CITYSCAPE:

phaseIIstudyoftheanti-TIGITantibodytiragolumabplusatezolizumabversusplaceboplusatezolizumabas1LinpatientswitthrePaDtm-Le1n-stelectedNSCLC,+Atezolizumab1200mgIVq3w,Placebo600mgIVq3w+Atezolizumab1200mgIVq3w,PDorlossofclinicalbenefit,StratificationFactors:

PD-L1TPS（1-49%vs50%）Histology（Non-SquamousvsSquamous）Tobaccouse（yesvsno）,Co-PrimaryEndpoints:

ORRandPFSKeySecondaryEndpoints:

Safet,DOR,OS,Patient-reportedoutcomes（PROs）ExploratoryEndpoints:

EfficacyanalysisbyPD-L1status,1LStageIVNSCLC,EGFR/ALKwild-type,TumorPD-L1TPS1%by22C3IHCbylocalorcentral