Advaxis与 Incyte达成肿瘤免疫联合疗法临床合作

2015年2月14日讯/生物谷BIOON/--肿瘤免疫界的潜力股公司Advaxis与专注于小分子药物的Incyte公司就他们各自的肿瘤免疫新药ADXS-HPV和Epacadostat达成了合作意向——对宫颈癌患者联合给药并进行临床研究。
这两种候选药都是处于研发阶段的肿瘤免疫新药，所谓肿瘤免疫疗法即辅助机体自身免疫系统对抗癌细胞，达到祛除肿瘤的目的。这个项目包括ADXS-HPV单独给药的Ⅱ期临床和两种药联合给药的Ⅰ期、Ⅱ期临床研究，该项目将会是多渠道、公开透明的研究，一共有二十位患者参与，探究其对HPV引起的宫颈癌的疗效和安全性。
Advaxis的CEODanielJ.OConnor表示他们对这次的合作感到激动，“在先前和目前的研究中，我们发现仅仅使用ADXS-HPV对患有复发性宫颈癌的女性给药，显著提高了患者的康复几率，我们相信这两种新药的联合使用会提高顽固癌症的治愈率。”
Incyte的首席研发专家RichLevy说：“肿瘤免疫疗法是肿瘤治疗的新希望所在，我们之所以与ADXS进行合作，也是希望尽快阐明Ido1抑制剂对多种癌症到底有没有疗效。”
实质性的合作将很快展开，这次合作的结果也会提示双方是否有必要进行后续研究。关于合作细节，双方并未透漏太多。
宫颈癌
每年，由HPV(人乳头瘤病毒）引起的新增乳腺癌患者高达50万例（WHO2010年报道）。HPV疫苗只是预防性的，并不能对已经感染HPV的两千万女性患者提供保护，而且疫苗中只含HPV16和18株，不含其他高致病性的毒株，再加上疫苗普及程度低、民众接受程度低，在美国只有大约1/3的女性患者接种HPV疫苗，在其他国家接种率就更低了。此外，HPV也会引发口腔鳞状细胞癌，发病率达20-40%。
ADXS-HPV
ADXS-HPV是Adxaxis公司主打的肿瘤免疫候选药，主要用来治疗由HPV引发的癌症，如宫颈癌、头颈部癌、直肠癌。该产品的Ⅱ期临床结果显示其明显提高了机体对肿瘤的应答率（宫颈癌），延长患者生命。无论是单独给药，还是与化疗相结合，其安全性都在可以控制的范围内。对头颈部癌和直肠癌的临床研究也正在进行中。ADXS-HPV也获得了FDA对其治疗罕见病的授权。
Epacadostat
Ido1（吲哚胺-2,3-双加氧酶）是一种抑制免疫系统的酶，抑制T细胞增殖和活化，帮助癌细胞逃避免疫监视。Epacadostat是Ido1的小分子抑制剂，可口服。生化和细胞水平的实验数据表明钠摩尔级别的剂量就有明显作用：刺激T淋巴细胞、树突状细胞和自然杀伤细胞的增殖活化，并具有高度选择性。Epacadostat与ipilimumab（百时美施贵宝产品，CTLA-4的小分子抑制剂）对于治疗不可切除的或转移性黑色素瘤的临床研究正处于概念验证阶段，与PD-1及PD-L1抑制剂联合应用于其他癌症的临床研究也正在进行中。
英文原文：
AdvaxisFormsClinicalTrialCollaborationWithIncytetoEvaluateInvestigationalCombinationofTwoNovelCancerImmunotherapiesforEarlyStageCervicalCancerPRINCETON,N.J.,Feb.11,2015(GLOBENEWSWIRE)--Advaxis,Inc.(ADXS),aclinical-stagebiotechnologycompanydevelopingcancerimmunotherapies,hasenteredintoaclinicaltrialcollaborationagreementwithIncyteCorporation(INCY)toevaluatethecombinationofAdvaxissLm-LLOcancerimmunotherapy,ADXS-HPV(ADXS11-001),withIncytesinvestigationaloralindoleamine2,3-dioxygenase1(IDO1)inhibitor,epacadostat(INCB24360).ThePhase2multicenter,open-label,preoperativewindow-studywillevaluatethesafetyandefficacyofADXS-HPVasamonotherapyandincombinationwithepacadostatinapproximately20patientswithStageI-IIahumanpapillomavirus(HPV)-associatedcervicalcancer.
BothADXS-HPVandepacadostatareinvestigationalcancerimmunotherapies,anewclassoftreatmentsthatusethebodysownimmunesystemtohelpfightcancer.
"WeareexcitedtocollaboratewithIncyteandtoevaluateepacadostatincombinationwithourleadingLm-LLOimmunotherapycandidate,ADXS-HPV,"saidDanielJ.OConnor,ChiefExecutiveOfficerofAdvaxis."Inpreviousandongoingstudies,asingletreatmentcycleofADXS-HPV,asamonotherapy,hasdemonstratedimprovementsinoverallsurvivalinwomenwithrecurrentcervicalcancer.Webelievethecombinationofimmunotherapiesmayholdsignificantpromiseforthetreatmentofthisdifficult-to-treatdisease."
Underthetermsoftheagreement,AdvaxisandIncytewillcollaborateonanon-exclusivebasistoevaluatethecombinationofADXS-HPVwithepacadostatforthetreatmentofcervicalcancer.Thecompanieswillcollaborativelyconductandfundthestudy,whichisexpectedtobeginlaterthisyear.Resultsfromthestudywillbeusedtodeterminewhetherfurtherclinicaldevelopmentofthiscombinationiswarranted.Furtherdetailsoftheagreementwerenotdisclosed.
"Webelieveimmune-targetedcombinationtherapyrepresentsapromisingnewapproachinoncology,"saidRichLevy,MD,ChiefDrugDevelopmentandMedicalOfficeratIncyte."ThisclinicaltrialcollaborationisafurtherillustrationofourdesiretoinvestigatethetherapeuticvalueofourIDO1inhibitorinmultipletumortypesasrapidlyaspossible."
Aboutcervicalcancer
Thereare500,000newcasesofcervicalcancercausedbyHPVworldwideeveryyear,accordingtotheWHOHumanPapillomavirusandRelatedCancersintheWorldSummaryReport2010.Currentpreventativevaccinescannotprotectthe20millionwomenwhoarealreadyinfectedwithHPV;andofthehighriskoncogenicstrains,onlyHPV16and18arepresentinthesevaccines.Challengeswithacceptance,accessibility,andcompliancehaveresultedinonlyaboutathirdofyoungwomenbeingfullyvaccinatedintheUnitedStatesandevenlessinothercountriesaroundtheworld.HPVisassociatedwith20-50%oforalsquamouscellcarcinomas.
AboutADXS-HPV
ADXS-HPVisAdvaxissleadimmunotherapyproductcandidateforthetreatmentofHPV-associatedcancers.ItiscurrentlyunderinvestigationinthreeHPV-associatedcancers:invasivecervicalcancer,headandneckcancer,andanalcancer.Incervicalcancer,arecentlycompletedPhase2studyofADXS-HPVdemonstratedapparentprolongedsurvivalandtumorresponsesincludingcompleteresponses,andamanageablesafetyprofilewhengivenaloneorincombinationwithchemotherapysupportingfurtherdevelopmentoftheImmunotherapy.Clinicaltrialsinheadandneckcancerandinanalcancerareongoing.AdvaxishasreceivedOrphanDrugDesignationfromtheUSFoodandDrugAdministrationforADXS-HPVtotreatinvasivecervicalcancer,HPV-associatedheadandneckcancer,andforanalcancer.
Aboutepacadostat(INCB24360)
Indoleamine2,3-dioxygenase1(IDO1)isanimmunosuppressiveenzymethathasbeenshowntoinduceregulatoryTcellgenerationandactivation,andallowtumorstoescapeimmunesurveillance.EpacadostatisanorallybioavailablesmallmoleculeinhibitorofIDO1thathasnanomolarpotencyinbothbiochemicalandcellularassaysandhasdemonstratedpotentactivityinenhancingTlymphocyte,dendriticcellandnaturalkillercellresponsesinvitro,withahighdegreeofselectivity.Epacadostathasshownproof-of-conceptclinicaldatainpatientswithunresectableormetastaticmelanomaincombinationwiththeCTLA-4inhibitoripilimumab,andiscurrentlyinfourproof-of-conceptclinicaltrialswithPD-1andPD-L1immunecheckpointinhibitorsinavarietyofcancertypes.

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