肺癌的免疫靶向治疗.ppt

*****PrimaryMaximumtolerateddoseHighestdosewithinacohortinwhichnomorethan1/6patientsexperiencedose-limitingtoxicities(DLTs)DLTevaluationperiodwasfromfirstdoseuntiladministrationof:ThirddoseofMEDI4736+tremelimumab(forthecohortreceiving3mg/kgMEDI4736q4wand1mg/kgtremelimumabq4w);orSeconddoseofMEDI4736+tremelimumab(othercohortsreceivingMEDI4736q4w);orThirddoseofMEDI4736andseconddoseoftremelimumab(cohortsreceivingMEDI4736q2w)SafetyandtolerabilityAdverseevents(AEs)andseriousAEs(SAEs)gradedaccordingtotheNationalCancerInstituteCommonTerminologyCriteriaforAdverseEventsVersion4.03(NCICTCAEv4.03)SecondaryAntitumoractivityAssessedbyResponseEvaluationCriteriainSolidTumorsVersion(RECIST)v1.1every8weeksPharmacokinetics(PK)MEDI4736andtremelimumabserumconcentrationsImmunogenicityExploratoryBiomarkersthatmaycorrelatewiththeclinicalactivityofMEDI4736incombinationwithtremelimumabTumortissuesamplestakenatbaselineandfollowingtreatmentforassessmentofPD-L1statusPD-L1immunohistochemicalstainingonautomatedBenchMarkULTRA?platformusingthePD-L1SP263assay(seeASCO2015Poster8033)SerumPD-L1expressiontestedretrospectivelyT-cellproliferationassessedbyflowcytometry*POPLAR:PD-L1ExpressionSubgroupsbr/TC1/2/3orIC1/2/3interimOS(n=195)PresentedByAlexanderSpiraat2015ASCOAnnualMeeting第31页,共62页，星期六，2024年，5月PD-L1单抗MEDI4736治疗晚期NSCLC的

安全性和疗效性2015ASCOabstract8032第32页,共62页，星期六，2024年，5月研究设计筛选12个月的治疗周期MEDI4736ivQ2w(0.1,0.3,1,3,10mg/kg)Q3w(15mg/kg)随访Day-28-1+1疾病进展疾病进展后，在随访期间的患者允许重新接受MEDI4736治疗主要终点：安全性和耐受性抗肿瘤活性探索终点：收集组织和血浆标本肿瘤的PD-L1表达状态(PD-L1检测方法：IHC[SP263]诊断检测)25例患者在治疗前后CD8+TIL的配对分析（CD28检测方法：IHC[SP57]检测）关键入组标准：组织学/细胞学证实NSCLCECOGPS0-1允许既往接受过抗CTLA-4治疗关键排除标准：自身免疫疾病既往发生严重的免疫相关性不良事件既往接受过抗PD-1和抗PD-L1治疗第33页,共62页，星期六，2024年，5月研究结果