默沙东PD-1免疫疗法Keytruda治疗恶性胸膜间皮瘤疾病控制率高达76%

2015年4月21日讯/生物谷BIOON/--默沙东近日公布了PD-1免疫疗法Keytruda（pembrolizumab）治疗实体瘤的一项Ib期KEYNOTE-028研究的首批数据。该研究是一项多组、非随机研究，在当前疗法不适合或无响应的320例PD-L1阳性晚期实体瘤患者中开展，旨在调查Keytruda（10mg/kg，每2周给药一次）单药疗法治疗20种难治性肿瘤的安全性、耐受性和抗肿瘤活性。
此次公布的是Keytruda治疗25例胸膜间皮瘤（pleuralmesothelioma，PM）患者的疗效和安全性数据。数据显示，Keytruda治疗取得了28%的总缓解率（ORR），此外有48%的患者病情稳定，疾病控制率达到了76%。在分析数据时，有40%（n=10/25）的患者仍然在接受治疗。该研究中，不良事件与以往报道的Keytruda安全性数据一致。治疗相关的最常见不良事件（发生于≥20%患者）包括疲劳（24%）、恶心（24%）。研究中未发生治疗相关不良事件的停药，也没有发生治疗相关的死亡事件。
相关数据已提交至4月18-22日举行的2015年美国癌症研究协会（AACR）年会上。据悉，这也是KEYNOTE-028研究的首批数据。
默沙东表示，该部分研究中所观察到的高达76%的疾病控制率数据非常鼓舞人心，支持了进一步调查Keytruda治疗恶性胸膜间皮瘤的临床潜力。
胸膜间皮瘤（PM）是一种原发于胸膜间皮的罕见、侵袭性、恶性肿瘤，治疗选择极其有限。外科手术是该病的主要治疗方法，术后辅助放疗能控制肿瘤的局部复发，并延长生存期。
英文原文：EarlyFindingswithKEYTRUDA®(pembrolizumab),Merck’sAnti-PD-1Therapy,inPatientswithAdvancedPleuralMesotheliomaPresentedatAACRAnnualMeeting
KEYTRUDADemonstrated28PercentOverallResponseRateand76PercentDiseaseControlRateinDifficult-to-TreatCancer
FirstFindingsfromKEYNOTE-028,Merck’sInnovativeBasketTrialin20Cancers
Sunday,April19,201512:45pmEDTPDFPrintPHILADELPHIA--(BUSINESSWIRE)--Merck(NYSE:MRK),knownasMSDoutsidetheUnitedStatesandCanada,todayannouncedthefirstpresentationofdatainvestigatingtheuseofKEYTRUDA®(pembrolizumab),thecompany’santi-PD-1therapy,in25patientswithadvancedpleuralmesothelioma,adifficult-to-treatcanceroftheliningofthelungs,abdomenandotherorgans.Theearlyfindingspresentedshowedanoverallresponserate(confirmedandunconfirmed)of28percentwithKEYTRUDAinpatientswithtumorsthatexpressedPD-L1.Additionally,48percentofpatientshadstabledisease,resultinginadiseasecontrolrateof76percent.Thesedata,fromKEYNOTE-028,willbepresentedtodayattheAmericanAssociationforCancerResearch(AACR)AnnualMeetingbyDr.EvanAlley,AbramsonCancerCenter,UniversityofPennsylvania,andwerepartoftheAACRofficialpressprogram(abstract#CT103).ThisisthefirstdatatobepresentedfromKEYNOTE-028,Merck’sinnovativebaskettrialdesignedtoevaluatetheefficacyandsafetyofKEYTRUDAinpatientswith20difficult-to-treatcancers.
“ThispresentationatAACRmarksthefirsttimethatdatainvolvingananti-PD-1therapyhavebeenpresentedinpleuralmesothelioma,whichisarare,hard-to-treatcancerwithverylimitedtreatmentoptions,”saidDr.Alley,clinicalassociateprofessorofmedicine,AbramsonCancerCenter.“Whileearly,thediseasecontrolratesobservedinthisstudyareveryencouraging,andindicatethatfurtherstudyiswarrantedtoevaluatethepotentialroleofKEYTRUDAinthetreatmentofmalignantpleuralmesothelioma.”
“ThisuniquestudyishelpingtoaccelerateourunderstandingofwhereKEYTRUDAmayworkincancerswithlimitedornotreatmentoptions,”saidDr.RogerDansey,therapeuticareaheadandseniorvicepresident,oncologylatestagedevelopment,MerckResearchLaboratories.“TheseearlydatainadvancedpleuralmesotheliomareinforcetheclinicallymeaningfulresultsweareseeingwithKEYTRUDAacrossmultiplecancers.”
Atthetimeoftheanalysis,40percentofpatients(n=10/25)remainedontreatment.AdverseeventsinthestudywereconsistentwithpreviouslyreportedsafetydataforKEYTRUDA.Themostcommontreatment-relatedadverseevents(occurringingreaterthantwentypercentofpatients)werefatigue(24%)andnausea(24%).TwoGrade3treatment-relatedadverseeventsoccurred:ALTincreased(n=1)andthrombocytopenia(n=1).Somepatientsexperiencedadverseeventsofspecialinterest,includingrash(n=4),ALT/ASTincreased(n=1),hypersensitivity(n=1)andiridocyclitis(n=1);tworequiredadoseinterruption(onebecauseofALT/ASTincreased,onebecauseofiridocyclitis).Nopatientsdiscontinuedasaresultoftreatment-relatedadverseevents,andtherewerenotreatment-relateddeaths.
AbouttheKEYNOTE-028Study
KEYNOTE-028isanongoing,multi-cohort,non-randomizedPhase1bbaskettrialevaluatingthesafety,tolerability,andanti-tumoractivityofKEYTRUDAmonotherapy(10mg/kgdosedeverytwoweeks)in320patientswithPD-L1positiveadvancedsolidtumorsthathavenotrespondedtocurrenttherapyorforwhichcurrenttherapyisnotappropriate.
AboutKEYTRUDA®(pembrolizumab)
KEYTRUDA(pembrolizumab)isahumanizedmonoclonalantibodythatblockstheinteractionbetweenPD-1anditsligands,PD-L1andPD-L2.BybindingtothePD-1receptorandblockingtheinteractionwiththereceptorligands,KEYTRUDAreleasesthePD-1pathway-mediatedinhibitionoftheimmuneresponse,includingtheanti-tumorimmuneresponse.
KEYTRUDAisindicatedintheUnitedStatesatadoseof2mg/kgadministeredasanintravenousinfusionover30minuteseverythreeweeksforthetreatmentofpatientswithunresectableormetastaticmelanomaanddiseaseprogressionfollowingipilimumaband,ifBRAFV600mutationpositive,aBRAFinhibitor.Thisindicationisapprovedunderacceleratedapprovalbasedontumorresponserateanddurabilityofresponse.Animprovementinsurvivalordisease-relatedsymptomshasnotyetbeenestablished.Continuedapprovalforthisindicationmaybecontingentuponverificationanddescriptionofclinicalbenefitintheconfirmatorytrials.
Merckisadvancingabroadandfast-growingclinicaldevelopmentprogramforKEYTRUDAwithmorethan85clinicaltrials–acrossmorethan30tumortypesandover14,000patients–bothasamonotherapyandincombinationwithothertherapies.
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