2018 - home - melanoma research alliance · annual melanoma research alliance scientific retreat...

I

SCIE

NTI

FIC

RET

REAT

TEN YEARS OF ACCELERATING CURES: Highlights from the Melanoma Research Alliance 10th Annual Scientific Retreat

2018

CONTENTS

1

LetterfromChiefScienceOfficerand ScientificProgramDirector 02

FutureChallengesInMelanoma 03

OptimizingtheUseofImmunotherapy 07

MRAResearchersExploringaDiverstity ofTreatmentStrategies 09

TacklingBrainMetastases 11

ApplyingArtificialIntelligencetoMelanomaDetection 13

MaintainingthePaceofMelanomaInnovationinthe EraofanEvolvingStandardofCare 14

Agenda 15

ParticipantList 19

RetreatSponsors 30

For the Melanoma Research Alliance (MRA), promoting collaboration and conversation among key stakeholders in the melanoma community is central to our mission. One way MRA achieves this is through our Annual Scientific Retreat, which this year was held February 28-March 2, 2018, in Washington, D.C, and marked the tenth anniversary of this important gathering. This invitation-only, think-tank style conference brings together nearly 300 academic investigators, pharmaceutical and biotech representatives, government officials, donors, and patient advocates.

At MRA’s Tenth Annual Scientific Retreat, participants heard about the latest discoveries in melanoma prevention, diagnosis, and treatment, many of which are being made by MRA-funded investigators. They also learned firsthand from individuals personally affected by melanoma and discussed ways in which the different sectors of the melanoma community can work together to ensure the momentum of the past decade of discoveries and treatment approvals continues.

Presentations and panel discussions touched on a variety of topics, spanning early discovery research to the latest changes in clinical practice. Researchers provided new insights into how melanoma metastasizes, including identifying new therapeutic targets. They also discussed factors that may influence whether patients will respond to immunotherapy, which include such things as the composition of a patient’s gut microbiome. Other highlights included recent practice changing results that emerged in the past year that impact patients with later stage, surgically removable melanoma. Together, the presentations highlighted the incredible progress of the past decade and illuminated the path forward so that all melanoma patients may have an effective therapy.

The Scientific Retreat also featured several satellite sessions, including the Young Investigators’ Breakfast and the Industry Roundtable, which engaged participants in conversations around effective collaboration and maintaining the rapid pace of progress in preventing, diagnosing, and treating melanoma, repectively. A group of melanoma patient advocates also gathered to learn from one another and to hear updates on the latest science from leading melanoma researchers.

We at MRA are delighted to host such important and productive conversations. We know they will spur the next wave of progress and lead to a day when suffering and death from melanoma will be a thing of the past.

Sincerely,

LETTER FROM CHIEF SCIENCE OFFICER AND SCIENTIFIC PROGRAM DIRECTOR

Louise M. Perkins, Ph.D. Chief Science Officer

Louise M. Perkins, Ph.D. Chief Science Officer

Kristen L. Mueller, Ph.D.Scientific Program Director

Kristen L. Mueller, Ph.D.Scientific Program Director

2

3

FUTURE CHALLENGES IN MELANOMA

3

4

TenyearsagowhenSamanthaStinchcomb’sfatherwasdiagnosedwithadvancedmelanoma,hisdoctortoldhisfamilytherewaslittlethattheycoulddotosavehislife.Hediedafewyearslater.“Fewerpatientsandtheirfamiliesarebeingtoldthatanymore,”Samanthatoldtheaudienceatthe10thAnnualMelanomaResearchAllianceScientificRetreatheldinWashington,DC,February28-March2,2018.

Thisthemeofprogressagainstthebackdropoffuturechallengesechoedthroughoutthe10thAnnualRetreat.FromtheopeninglecturebyDr.SuzanneTopalianon“ADecadeofProgressinMelanoma”totheIndustryRoundtablethatfocusedon“MaintainingthePaceofMelanomaInnovationintheEraofanEvolvingStandardofCare”–successesandremainingchallengeswereputinfocus.

Intheopeninglecture,Topalian,ofJohnsHopkinsUniversity,summeduptheadvancementssaying“thisishead-spinningprogress.”Tenyearsago,advancedmelanomapatientsonlyhadthreetreatmentoptions,andnoneofthemwerethateffective.Now,incontrast,thereare11FDA-approvedtherapiesforthissamegroupofpatientsandabouthalfofthesepeopleexperiencesubstantialbenefit.

ButTopalianandseveralotherclinicianswerequicktopointout,thatwhiletheglassishalffull,itisalsohalfempty.Inshort–toomanypatientswithmetastaticmelanomastilldiefromthiscancer.Overhalfofpatientswithcutaneousmelanomaeitherfailtorespondorrelapseearly,despitereceivingthelatesttreatments.Moreoveritisstillparticularlydangerousforpatientswithocular,acral,orotherrareformsofmelanoma,forwhomcurrenttreatmentsarenotusuallyaseffectiveastheyareforthemorecommoncutaneousmelanomasthatariseonsun-exposedpartsoftheskin.“Therearestillpocketsofneedthathavetobeaddressed,”notedDr.JeddWolchokofMemorialSloanKetteringCancerCenter.

Putting MRA Out of BusinessAtthisgatheringof300ofthebestandbrightestmelanomaclinicians,researchers,advocatesandotherkeysstakeholders,muchofthediscussionfocusedonwhatneedstobedonenexttocuremelanomaand“putMRAoutofbusinessassoonaspossible,”asMRAco-founderDebraBlacksuccinctlyputsit.Ideaswereplentiful;includingfurtheringourunderstandingofthebiologyofrare,hard-to-treatmelanomasubtypesandthetumormicroenvironment,whichcontainsavarietyofcelltypesthatcanimpactonwhetheratherapywillwork,aswellasdevelopingbetterwaystopredictwhichpatientsarelikelytorespondtowhichtreatments.Improvingtheunderstandingandtreatmentofdrugresistancealsocontinuestobeamajorfocusofresearch,alongwithdeterminingwhichdrugstocombinetobesttreatmelanomapatients.

Stopping Melanoma From Coming BackParticipantsalsostressedtheimportanceofpursuingearlier-stagetreatmentavenuesthatarecurrentlygainingmomentumintheclinic.Oneistreatingpatientswithhighrisk,butsurgicallyremovablemelanomas,withvarioustherapiestoreducetheriskofmelanomacomingback(adjuvanttherapy).Sometherapies,suchasinterferon,ipilimumab,nivolumabandcombinationDabrafenibandTrametinib,arealreadyapprovedintheadjuvantsetting,andothertreatmentshaveshownpromisingresultsinrecentclinicaltrials.Asecond,relatedstrategy,calledneoadjuvanttherapy,involvestreatingmelanomapatientstoreducethepresenceofcancerpriortoremovingtheirtumorssurgically.

Samantha Stinchcomb

Suzanne Topalian

5

FUTURE CHALLENGES IN MELANOMA (CONT.)

Earlyclinicalresultsforneoadjuvanttherapyshowrealpromise;however,noneoadjuvanttherapiesarecurrentlyFDA-approved.Giventhegame-changingnatureoftheseapproaches,expertsstressedtheimportanceofdesigningclinicaltrialsandstudiesinawaythatrevealhowthedrugsareworkinginmelanomaandthesurroundingcellularenvironments.Thiscouldbecriticalinformationtoimprovethewaywetreatmelanomaforallpatients.

When Should Patients Stop Treatment?Anotherconceptthatgeneratedbuzzamongparticipantswaswhenandhowtostopdrugtherapyformelanomapatients.Forexample,theimmunotherapydrugsnivolumabandpembrolizumabaregiventopatientsuntildiseaseprogressionorunacceptablesideeffectsdevelop.Withinfusionsrequiredevery2-4weeksdependingonthedoseanddrug,thisisasubstantialburden,especiallyforthosepatientswhorespondlong-term.Putbluntly,researchersjustdon’tknowhowlongthesedrugsneedtobetakentobemosteffective.Dr.PatrickHwuoftheMDAndersonCancerCenterstressedthatstoppingsuchtreatmentsshouldbeaccompaniedbysurveillanceforearlyrecurrenceofmelanoma,butalsonotedthatweneedbetter,noninvasivemethodstodetectrecurrence.OnepromisingwaytodothismightbetouseatestformelanomatumorDNAcirculatingintheblood,knownasliquidbiopsies.Anearlyclinicaltestofthisincoloncancerenableddoctorstodetectarecurrenceupto6monthspriortothecancerbeingseeninascan.Inaddition,Topalian,Wolchok,andDr.GeorginaLongoftheUniversityofSydneystressedtheneedto

researchwhetherperiodic‘booster’treatmentswouldimprovethelong-termeffectivenessofmelanomadrugs,particularlywithinthecontextofimmunotherapies.

Aligning Basic and Clinical ResearchDr.RichardMaraisofCancerResearchUKManchesterInstitutepointedoutthatthefastpaceofmelanomaresearchrequiresfrequentinteractionbetweenbasicandclinicalresearchers.HenotedthatthelaboratoryworkdelineatingthemolecularpathwaysthatdrivemelanomaledustotargetedtherapiesknownasBRAFandMEKinhibitorsandimmunotherapies,andsuggestwaystoovercometreatmentresistance.Maraisstressedthecontinuedneedtounderstandthebasicbiologyofmelanomaanditstreatments,andforbasicbiologyresearcherstoexploreanswerstoquestionsthatarerelevanttoclinicians.“AnamazingMRAachievementhasbeentocreateacommunitywherebasicandclinicalresearcherscanmeet.Thediscussionswe’vehadherewillcontinueatothermeetings,”Maraissaid.AsMRAPresidentandCEOMichaelKaplanstressedinhisclosingstatementattheretreat,“Wetakeseriouslytheword‘Alliance’inMRA’sname.”

Collaborating for SuccessTheneedforevermorecollaborationamongmultiplesectorswasstressedbyalltypesofstakeholders,includingrepresentativesfromindustryandthefederalgovernment,aswellasbyacademicresearchersandpatients.Drs.RichardPazdurandMarcTheoretoftheFDAnotedthecollaborationstheiragencyfosteredsothatseveralcancerbiomarkersordrugsfrommultiplecompaniescanbetestedconcurrentlyinthesameclinicalstudy.TheFDAhasalsobeguninteractingwithdrugcompaniesearlierinthedrugdevelopmentprocesstoensuredrugsponsorscollecttheinformationneededforregulatorydecisions.

Severalindustryparticipantsnotedthenumerousstudiesalreadyunderwayinwhichdrugcompaniesarecollaboratingwitheachothertoclinicallytestcombinationtherapies,andDr.EladSharonfromtheNationalCancerInstitute(NCI)notedthathisagencyworkscloselywiththeFDAandpharmaceuticalcompaniestomakesuregovernment-sponsoredtrialsareinnovativeandnotduplicatingwhatindustrycandoonitsown.“Thereisanunprecedentedlevelofcollaborationnow,”Pazdurnoted,butadded“everyonehastheirownfavoritedrugthattheywanttotest.”HesuggestedNCIcouldhelpensurethatthemostpromisingcombinationsareenteringclinicaltrials.

“Weneedtobreakdownthecommercialbarrierssowecangetthemoleculestogetherthatwillgiveusthebestoutcome,”saidLong,andshealongwithDr.CarolineRobertofInstitutGustaveRoussyaddedtheimportanceofsharingdatainordertostreamlinethedevelopmentofdrugsandbiomarkerteststhatwouldhelpphysiciansgivetherighttreatmenttotherightpatient.Georgina Long

6

Designing Clinical Trials of the FutureTheFDAalongwithacademicandindustryscientistsareworkinghand-in-handtoensurethatclinicaltrialsareproducingthehighestqualitydatapossiblewhilebalancingtheneedtogetlifesavingtreatmentstothepeoplewhoneedthemthemostasquicklyaspossible.TheFDAhasdemonstrateditswillingnesstobeflexibleinthetypesofdataandstudiesitwillacceptforitsapprovalofnewcancerdrugssoastospeedtheentryofneweffectivetreatmentsintotheclinic.AccordingtoPazdur:“Itusedtobethatyouhadtopresentdatafromarandomized,controlledtrialorgohome,butthat’snolongerthecase.”

Inclinicaltrials,anendpointistheprimaryoutcomethatisbeingmeasured.Inoncology,thisisoftenacomparisonofthedurationofpatientsurvivalorlengthoftimebeforeprogressionusingtheexperimentaltherapycomparedtothoseusingthestandardofcare.Severalresearchersadvocatedfortheneedtodevelopadditionalendpointsinclinicaltrialstodetermineifatreatmentiseffective.Thesecouldbepatient-reportedoutcomes,circulatingtumormarkersorameasureoftumorcellsintissuesamplesremovedduringsurgeryorbiopsy.Suchexpandeddefinitions ofsuccesswillfurtheracceleratethedevelopmentofnewmelanomatreatments.

Mostclinicaltrialssetstricteligibilitycriteriainordertominimizetheeffectofotherfactorsthatcouldobscuretheeffectoftheexperimentaldrug.However,strictcriteriarestrictpatientenrollment,limitaccesstotheexperimentaltherapy,andmaymaketrialresultslessgeneralizabletoreal-worldpatientpopulations.Forexample,abouthalfoflate-stagemelanomapatientshavebrainmetastaseshoweverpeoplewithbrainmetastaseshavebeenhistoricallyexcludedfrommoststudies.Severalresearchersadvocatedforadoptingmodernizedclinical

trialeligibilitycriteriatoincludethesegroupsandotherstobothspeeddrugdevelopmentandprovidebetterinsightintoefficacyandside-effectsearlier.

Bringing Research HomeWhenSamanthaStinchcomb’sfatherdiedin2010,shethoughtthechapterofherlifethatintersectedwithmelanomawasover.Sadly,thathasnotbeenthecase.Fartoooften,saidStinchcomb,sheleavesherdermatologist’sofficeintearsbecauseofthenumerousprecancerousmolesdetectedonherskinthatwilllaterneedtoberemoved.Sheiscomfortedbytheincredibleprogressbeingmadeinthetreatmentoflate-stagedisease,butknowsthatmoreworkisneededtoensuretheendofsufferinganddeathduetomelanomaonceandforall.“Researchtoendmelanomasoundsgoodtome.Yourworkmeansmoretomorrows,”saidStinchcomb.

Richard Pazdur

“ Research to end melanoma sounds good to me. Your work means more tomorrows”

Debra Black

7

Perhapsthedecade’sgreatestachievementinmelanomatreatmenthasbeentheFDAapprovalofcancerimmunotherapytreatmentscalledcheckpointinhibitors.Thisclassofdrugsincludeipilimumab,nivolumabandpembrolizumab.Thesetherapiesharnessthepoweroftheimmunesystemtofendoffdisease–includingmelanoma.Manypatientstreatedwiththesedrugsexperiencedurableresponses,andinafractionofpatientsexpertssuspectthedrugsarecurative.

Predicting Response and RecurrenceWhileimmunotherapyhasbeenanincredibleadvance,thereisstillroomforimprovement.Forexample,onlyabouthalfofpatientswithadvancedmelanomarespondtothesetreatments,andinsomecases,patientsmaynotseetheirtumorsstarttoshrinkuntilseveralmonthsafterstartingtherapy.Thisisproblematicbecausesomepatientswithadvanceddiseasehavewidespreadandbulkytumors.Inaddition,immunotherapycansometimestriggerserious,andattimesirreversible,autoimmuneconditionssuchasthyroiddysfunctionordiabetes.Researchersdonotyetunderstandwhysomepeopledevelopthesesideeffectsandothersdonot.Thisisespeciallyimportantasphysiciansincreasinglyturntoadjuvantimmunotherapyforearly-stagemelanomapatients,whereasubstantialfractionofpatientsmayneverexperiencearecurrenceaftertheirprimarymelanomaisremoved.

“We’vemadetremendousprogressinthetreatmentofcancerwithimmunotherapy,butresponsesaren’tuniversalandnotalwaysdurable,soweneed[betterpredictive]markersofresponse,”stressedDr.JenniferWargoofMDAndersonCancerCenter.

Tohelpunderstandwhichpatientswithadvancedmelanomawillbenefitfromimmunotherapy,researchersaretryingtoidentifymolecularfeatures–calledbiomarkers–intumorsorinthepatient’simmunecellsthatcanpredictaneffectiveresponsetotreatment.Forpatientswithearly-stagemelanoma,researchersaresearchingforbiomarkersthatindicatehighrecurrencerisk.SeveralMRA-fundedresearchersreportedontheirgroundbreakingeffortstofindthesebiomarkersatthelatest MRAscientificretreat.

TotrytoidentifybiomarkersthatcanpredictriskofrecurrenceinStage2or3surgicallyremovablemelanoma,Dr.YvonneSaengerofColumbiaUniversityinNewYorkCityexaminedpatients’tumorsamples.Shediscoveredthataparticularpatternofgeneexpression,aswellasthepresenceofonetypeofimmunecell,calleda‘killer’Tcell,andtheabsenceofanother,calledamacrophage,werecorrelatedwithagreaterlikelihoodoflong-termsurvival.“Wehopethiswillhelppatientsdecidewhether theyshouldget[adjuvant]immunotherapyaftersurgery,” Saengersaid.

Melanoma at Single Cell ResolutionDr.IdoAmitoftheWeizmannInstituteofScienceinIsraelpresentedhisworkusingpowerfulnewsinglecellsequencingandimagingtechnologieshedevelopedtodetermineinfinedetailthedifferentimmunecellsubtypeswithinandsurroundingtumors.“Whenwewantedtoidentifybiomarkersofrespondersversusnon-responderstotreatment,wesawacomplexzooofmanydifferenttypesofimmunecellsandfunctionsintumorsamplesthatcurrentmarkerscouldn’tdescribe,”hesaidwhenexplainingwhyhedevelopedthesetechniques.“Thetumormicroenviormentisextremelycomplex,yetunderstandingthesecellsandhow

OPTIMIZING THE USE OF IMMUNOTHERAPY

Ido Amit

Yvonne Saenger

8

theychangeinpatientsiscriticaltoidentifynewmarkersforrapidandeffectivetumorcharacterization,andidentificationofnovelimmunemodulatorypathways.”

OneofAmit’stechnologiescalled‘singlecellRNAsequencing’essentiallyprovidesasnapshotofallthegenesexpressedbyanindividualcellpluckedfromatumor.Theadvantageofthistechnologyisthatitgivesresearchersamuchmorecompletepictureofthecomplexnetworkofcellsthatmakeupatumoranditssurroundingtissue.Sofar,Amithasusedhistechniqueontumorsamplesfrom26patientswithmelanomaandhasuncovered“verydramaticdifferencesbetweenpatientsinthetypesofTcellsseenintheirtumors,”hesaid.Hisresearchidentifiedspecificpopulationsofimmunecells,someofwhichkilltumorsandothersthatblocktheanti-tumorimmuneresponse.“Oursingle-celltechnologiesprovideunprecedentedopportunitiestodrawamoreaccuratepictureofthevariouscelltypesandunderlyingtumor-immuneinteractionsandresponse totherapies,”.

Can the Microbiome Predict the Effectiveness of Immunotherapy?Otherpromisingtreatmentresponsebiomarkersarenotfoundonpatients’tumororimmunecells,butratherinthemorethan100trillionmicrobesthatinhabittheirbodies,especiallythosethatresideinthegut.Thisecosystemofmicrobes,collectivelyknownasthehumanmicrobiome,hasbecomeamajorfocusofcancerresearch,asmountingevidencerevealsitmayalterourriskofdevelopingvariouscancersandhowapatientmayrespondtoimmunotherapieslikepembrolizumab,nivolumab,andipilimumab.

Dr.ThomasGajewskioftheUniversityofChicagofoundthatcertainbacterialivinginthegutofmelanomapatientswerelinkedtopatients’abilitytorespondtoimmunotherapytargetingthePD-1molecule.Couldgutbacteriabeabiomarkerforresponsetoimmunotherapyinmelanomapatients?“It’scertainlyonparwith

otherbiomarkersenrichingforresponders,”Gajewskisaid,butaddedthat,“Themicrobiomeisn’teverything.Tumormutationfactorsmatter,andgermlinepolymorphismsarealsolikelyimportant.Butitcouldbeabetterbiomarkerthanmutationalloadandshouldbeexploredfurtherandintegratedwithothers.”

Inmousemodels,Gajewskifoundtransferringtheimmuneresponse-promotingbacteriatomicewithmelanomaviastooltransplantsimprovedtheirresponsetoimmunotherapy.Thissuggeststhatthemicrobiomemaynotonlyserveasaresponsebiomarker,butthatonedayprobioticsdesignedtocontain‘good’bacteriamayimprovethetreatmentofpatientswholackinflamedtumors.

Inanindependentsetofrelatedstudies,WargofoundthatthemicrobiomeofpatientswithmelanomawhorespondedtoPD-1-targetingimmunotherapydifferedfromthosewhodidnot.LikeGajewski,shealsofoundthatanabundanceofcertainbacteriainthegutcorrelatedwitha“hot”immuneresponsetotumors,whileahighabundanceofotherspecieslinkedtoa“cold”response.AbundantBifidobacteriumspeciesdidnotsurfaceasamajorindicatorofresponseinWargo’sstudies,asitdidinGajewski’sresearch.ButthemicrobialsignatureWargofoundthatindicatedaneffectiveresponsetoimmunotherapyhasalsobeenreportedbyresearchersstudyingpatientswithlungandkidneycancertreatedwithcheckpointinhibitors,Wargonoted.Sheandothersarecurrentlytestinganumberofstrategiestoseeiftheycanimproveresponsestoimmunotherapiesinmelanomaandothercancerpatients.“Canwemodulatethegutmicrobiometoenhanceresponsestoimmunotherapy?Yes!Butthatneedstobetestedwithinaclinicaltrial,”Wargostressed.

Thomas Gajewski

Jennifer Wargo

9

Overthepast10years,wehavemadetremendousstridesinthetreatmentofmelanoma,with11newtreatmentsearningFDAapproval.Butlessthanhalfofpatientsrespondtothesetreatments,meaningthatthebattleagainstmelanomaisfarfromoverandmoretreatmentsaredesperatelyneeded.MRA-fundedresearchersarepursuingpromisingnewstrategies-likeblockingmelanomametastasis;findingnewdrugtargets;orputtinganolddiabetesdrugtoworkagainstmelanoma–tobettertreatandultimatelycuremelanoma.

Preventing Melanoma SpreadDr.MarisolSoengasoftheSpanishNationalCancerResearchCenterisworkingonbetterunderstandingwhysomepatientswithmelanomaseetheircancerspreadrapidlyfollowingsurgery,whileothersdon’t.Usinggeneticallyengineeredmouseandzebrafishmodels,whichenableliveimagingoftheearlymetastaticprocessasitunfolds,Soengas’teamdiscoveredaproteincalledMidkine,whichmelanomacellsproducebeforetheyspreadthroughoutthebody.Midkinehelpstorolloutthewelcomematformetastatictumorcellsbymakingthesesites‘permissive’locationswheretheycantakeupresidence,essentiallypavingthewayformetastasis.ThemoreMidkineproduced,theworsetheprognosisforthepatients.

Dr.AshaniWeeraratnaoftheWistarInstitute,amemberofSoengas’L’OrealParis–MRAteam,exploredtheeffectsofagingonmetastasis.Todothis,shecomparedatypeofskincellcalledfibroblastsfrompeople25to35yearsoldwiththosefromolderindividuals.Shefoundthatfibroblaststakenfromolderpeopleproducedanalteredarrayofproteinsthatpromotedmetastasis.Proteinsproducedbythese‘aged’fibroblastsinstructedtumorcellstomigratetoandcolonizelymphnodes,andpromotedthegrowthofbloodvesselsneededtosupportthegrowthoftumorcellsatmetastaticsites.SoengasandWeeraratnaplantotestexperimentaldrugsthattargettheseandothermetastasis-supportingmoleculesinclinicaltrials.

Blocking Tumor Escape

Dr.KaiWucherpfennigofDana-FarberCancerInstitutereportedonhislatestfindingsonMICA,amoleculefoundonthesurfaceofstressedordamagedcellsthatsignalstotheimmunesystemthatthesecellsshouldbekilled.TumorcellsaresmartandshedMICAfromtheirsurfacetoevadedeath.Infact,patientswhoshedhighamountsofMICArespondedpoorlytotheimmunecheckpointinhibitoripilimumab,suggestingthatsheddingMICAhelpsmelanomaevadetheanti-tumorimmuneresponse.Toovercomethis,WucherpfennigdevelopedanantibodythatinhibitsMICAsheddingbytumorcells.WhenWucherpfennigtestedtheantibodyinmicewithmelanoma,hefounditreducedthenumberoflungandlivermetastases.Wucherpfennigplanstostarttestingtheantibodyinpatientswithcancerwithinthenextyear,withthehopesitwillenhancetumorkillingbytheimmunesystem.

Adding Radiation Therapy to Enhance Checkpoint BlockadeDr.RobertVonderheideoftheUniversityofPennsylvania’sAbramsonCancerCenterexploredapotentialsynergisticcombinationtreatmentformelanoma—radiationtherapyfollowedbytreatmentwithimmunotherapy.Vonderheidewaspromptedtoexploreifradiationcouldjumpstartanimmuneresponseafterapatientwithadvancedmelanomawhodidnotrespondtotwodifferentimmunotherapyagentswasgivenradiationtherapytorelievepainhewasexperiencingfromatumorinhischest.Strikingly,thepatiententeredanearlycompleteremission,whichisstillongoingmorethan7yearslater.Moreover,asmallsubsetofpatientsexperiencedtumorregressioninanearlystageclinicaltrialtestingthecombinationofradiotherapyandtheFDA-approvedimmunotherapyipilimumab,suggestingthepromiseofthiscombinedapproach.

Vonderheideandhiscolleaguesnextturnedtomousemodelstobetterunderstandhowradiationtherapyandimmunotherapysynergize,andrevealpotentialcausesofwhythisapproachdoesn’tworkinallpatients.Forinstance,whentheresearcherscomparedtumorsthatrespondedtothecombinationofradiotherapyandtheCTLA-4inhibitoripilimumabtothosethatdidnot,theyfoundhighlevelsofamoleculecalledPD-L1onthesurfaceofnon-respondingtumorcells.AddingaPD-1inhibitor,similartonivolumaborpembrolizumabtoipilimumabandradiotherapyimprovedresponsesinmice.Thissuggeststhatathree-partcombinationmayleadtoimprovedresponsesinpatients.“Thebottomlineisthatthreetreatments—ananti-CTLA-4drug,ananti-PD-L1drug,andradiationallhavedifferentmechanismsofactionsoshouldbesynergisticwhencombined,”Vonderheidesaid.Heandhiscolleaguesarecurrentlytestingsuchcombinationsinmultipleclinicaltrials.

MRA RESEARCHERS EXPLORING A DIVERSITY OF TREATMENT STRATEGIES

Marisol Soengas

10

Beyond BRAF MutationsMRA-fundedresearchersarealsoactivelypursuingnewtreatmentstrategiesthatfocusongeneticchangesinmelanomaitselfthatgobeyondBRAFgeneticmutations.Forexample,anothertumor-fuelingalterationinvolvesmoleculesthatinsteadareinvolvedinregulatinggeneactivityandtheproductionofproteinsthataffecttumorgrowth.Thereismountingevidencethatthesegene-regulating“epigenetic”factorscanplayamajorroleinfomentingcancersandthuscouldbeeffectivedrugtargetsformelanoma.

Dr.EmilyBernsteinoftheIcahnSchoolofMedicineatMountSinaireportedonanewmethodfordetectingepigeneticchangesthatpromotetumors.Usingthismethod,shediscoveredaproteincalledAMIGO2thatcouldserveasanoveldrugtarget.UnlikeBRAFandothergeneticflawsthatdrivetumorgrowth,nomutationsarefoundinthegeneencodingAMIGO2inmelanoma.Instead,melanomacellscontainmuchhigheramountsoftheAMIGO2proteincomparedtonormalcellsandthisincreasedexpressionisessentialformelanomacellsurvival.AMIGO2isatargetofagroupofexperimentaldrugscalledBETinhibitorsthatarecurrentlybeingtestedinclinicaltrials.“Theepigenomeisanimportantnewareaofbiologyandcancerthatisveryexcitingandexperimentaldrugstargetingitarerapidlymovingintotheclinic,”stressedBernstein.

Reviving an Old Drug to Treat MelanomaIncontrasttoBernstein’sreportsonnewlydeviseddrugs, LewisCantleyofWeillCornellMedicalSchoolreportedonan olddrugthatmaybeputtoanewusefightingmelanoma. Thedrugphenforminwasdevelopedasadiabetestreatmentandwasabandonedafteritprovedtootoxicinasmallsubgroupofpatients.Recognizingthatthemolecularactionsofphenformin

mightbeusefulinthetreatmentofmelanoma,CantleytesteditincombinationwithFDA-approvedtargetedtherapiesformelanoma.HefoundthecombinationofphenforminandtheBRAFinhibitorvemurafenibwassynergisticinaBRAFmutantmelanomamousemodel.Further,CantleyfoundthatphenformineffectivelykilledmelanomacellswithNRASmutationsinculturewhenitwascombinedwiththeFDA-approvedMEKinhibitortrametinib.ThisisimportantbecausenotherapiestargetingNRAS-mutantmelanomahavebeenFDAapproved.CantleyalsodiscoveredthatphenforminenhancesPD1-targetingimmunotherapiesformelanomainmousemodels.

CantleyandcolleaguesDr.PaulChapman(MemorialSloanKettering),Dr.JonathanZippin(WeillCornellMedicine)andDr.BinZheng(MassachusettsGeneralHospital)arecurrentlytestingthesafetyofphenoforminincombinationwithdabrafenibandtrametinibinpatientswithmelanoma.Sofarthisstudysuggestsphenformincanbesafelygiventopatientsatdoseslikelytobeactiveinfightingtheirtumors.Cantley’sfutureanalyseswillassesstheeffectsofphenforminonmelanomatumorbiologyandimmunecelldynamicsinpatientswithmelanoma.

Collectively,thesestudieshighlighthowresearchersareattackingmelanomaonmultiplefronts.Byfundingsuchgroundbreakingwork,MRAisdrivingcriticaldiscoveriestowardthenextgenerationofmelanomatreatments.

Robert Vonderheide

Emily Bernstein

11

Brainmetastases(mets)areafrequentandoftendeadlyprobleminpatientswithadvancedmelanoma.Nearly40%ofpatientswithmetastaticmelanomahavebrainmetsatdiagnosis,withanaveragesurvivalofonly4months,suggestingacrucialneedfortreatmentsthatcanridthebrainofthesetumors.1,2Butnewcancertreatmentsarerarelytestedinpatientswithactivebrainmets.Thisislargelyduetoconcernsaboutwhetherthesepatientswillhavesideeffectsuniquetobrainmets,andpooreroutcomesthatmaynegativelyweighagainstotherwisepositiveclinicalbenefits.Anotherpotentialconcerniswhetherthedrugswillevenpenetratethebrain,whichhasafortress-likeabilitytokeepsubstancesfromenteringit.

Fortunately,MRA-fundedresearchersaremakingheadwayinunderstandingbrainmetsandhowtobesttreatthem.Reportingfromthisexcitingresearchfrontier,threeinvestigatorsatthe2018MRAScientificRetreatpresentedtheirfindingsonhowtheuniquebiologyofthebrainsupportsbrainmets,whatpredictswhetherbrainmetswillrespondtotreatment,andwhatnewtherapiesmightbeespeciallyeffectiveatdestroyingthesetumors.

Evaluating the Effectiveness of FDA-Approved Therapies in Treating Brain MetsBecausepatientswithbrainmetsarefrequentlyexcludedfromclinicaltrials,cliniciansdonotfullyunderstandhowpatientswithbrainmetsrespondtoevenFDA-approveddrugs.Tohelpovercomethis,Dr.MichaelDaviesoftheUniversityofTexasMDAndersonCancerCenterstudiedtheresponseofmelanomapatientswithbrainmetstotreatmentwithdabrafenibplustrametinib.Thistargetedtherapycombinationblocksspecificproteinsthatfuelthegrowthoftheapproximately50%

ofmelanomasthatcontainmutationsintheBRAFenzyme.Theaverageprogression-freesurvivalofpatientsinthestudywas11months,approximatelyhalfthetimeofwhatpatientswithoutbrainmetscanexpectwhoaregiventhesametreatment.Notably,tumorsinpatients’brainsoftenprogressed,whiletumorsoutsidethebraindidnot.“Thetreatmentdidn’tworkaswellinthebrainasoutsidethebrain,”stressedDavies,whowaspuzzledbythisfinding,andconductedtwoadditionalstudiestofindoutwhythiswasso.

Thesefollow-upstudiescomparedtumorbiopsiestakenfromapatient’sbrainmetsandcomparedthemtoothertumorsamplesfromthesamepatient.Theresearchsuggeststhatbrainmetstendtohaveanoveractivetumor-fuelinggrowthpathwaythatisnotdirectlytargetedbydabrafenibandtrametinib.Moreover,immunesystemprofilingindicatedweakenedanti-tumorimmunityinbrainmetscomparedtothoseinothersites,suggestingthatcancerimmunotherapiesmayalsobelesseffectiveinthebrain.Altogether,Davies’studieshighlighttheneedforcontinuedresearchtoevaluatetheeffectivenessofalreadyapprovedtherapiesintreatingbrainmetsandrevealpotentialtherapeuticvulnerabilities.

Whetherimmunotherapiescanshrinkmelanomabrainmets,andwhatbiomarkersrelatetosuchaneffect,isalsoanunder-exploredterritory.InasmallstudyreportedbyDr.LuciaJilaveanuofYaleUniversity,pembrolizumabreducedthesizeofbrainmetsinapproximately25%ofmelanomapatientstreated.Thisquarterofpatientsalsoexperiencedsignificantshrinkageintumorslocatedoutsideofthebrain.Jilaveanususpectsthatusingcombinationsoftreatmentsmightimprovetherelativelylowresponserate,andthatbiomarkersmaypredictwhichpatientswillrespond,allowingclinicianstotargettreatmentstothosepatients.

TACKLING BRAIN METASTASES

Michael Davies

Lucia Jilaveanu

12

Jilaveanu’steamthenexaminedbrainmetsamplesremovedfrompatientspriortotreatmentwithpembrolizumab.Comparedtopatientswhosediseaseprogressedwhileontreatment,responders’sbrainmetshadhighernumbersoftumor-fightingTcells,andtheirbrainmetsalsoproducedmorePD-L1molecules,whichispartofthemolecularpathwaytargetedbypembrolizumab.Shealsofoundthatpatientswithbrainmetswhorespondedtopembrolizumabexperiencedareductionintheamountofedema,orexcessfluidaccumulatingintheirbrains.Edemacanbedisruptive,andattimesdeadly,forpatientswithbrainmets,andtherewasconcernthatimmunotherapiesmightaggravateit.ButatleastinJilaveanu’sstudy,thisprovednottobethecase.“Thisshouldlessenconcernsofusingthesetreatmentsinthesepatients,”shesaid.

Probing the Biology of Melanoma Brain MetsDr.ManuelValienteoftheSpanishNationalCancerResearchCenterfocuseshisresearchonthecellularenvironmentsurroundingbrainmetsinanefforttounderstandhowthis‘tumormicroenvironment’allowsbrainmetstodevelopandprogress.Hesoonrealizedthatthoughmanytumorcellsarriveinthebrain,onlysomebecomemetastatictumorslargeenoughtobedetectedonascan.“Metastasisisnotjustamatterofgettingthere—therealpictureismorecomplex,”Valientesaid.Hethensetouttoexplorethiscomplexitybystudyingbothanimalmodelsofmelanomaandbrainmetbiopsies.

Thisresearchuncoveredthatstar-shapedbraincellscalledastrocytesarepresentinthetumormicroenvironmentofbrainmetsandsecretemolecularsignalsthattriggertumorgrowth.WhenValienteblockedthissignalinginmicewithmelanomaorlungcancer,hefounditreducedthenumberandsizeofbrainmets.Hethentestedanexperimentaldrugthatinhibitsthesamemolecularpathwayinasmallnumberofpatientswithbrainmets.Amajorityofthesepatientsexperiencedareductioninthetumorburdenintheirbrain,whereasnosubstantialreductionswereseeninthesizeoftumorsoutsidethebrain,highlightingthelikelydifferentunderlyingbiologyofbrainmetscomparedtoothersites.“Weareexcitedabouttheseresultsandhopetostartaclinicaltrialoftheinhibitorsoonincancerpatients,”Valientesaid.

BecausethestudiesconductedbyDavies,Jilaveanu,andValienteallincludedrelativelysmallnumbersofmelanomapatients,theirfindingswillneedtobeverifiedinlargercohortsofpatients. Buttheglimmersofinsightintobrainmetsshouldultimatelyhelp treatpatientswiththesetumors.“Ifwecanidentifymolecularpatternsinbrainmetastases,wecanexploitthemtherapeutically,” Valientestressed.

Manuel Valiente

1.GlitzaIC,HeimbergerAB,SulmanEP,etal.Prognosticfactorsforsurvivalinmelanomapatientswithbrainmetastases.In:HayatM,editor.Brainmetastasesfromprimarytumors.AcademicPress.2016.pp.267–292

2.DaviesMA,LiuP,McIntyreS,etal.Prognosticfactorsforsurvivalinmelanomapatientswithbrainmetastases.Cancer.2011.117:1687–96

13

Ithasbeensaidthat“melanomawritesitsmessageontheskinwithitsowninkforallofustosee,sowhyisitsohardtodetect?”askedDr.SusanSwetterofStanfordUniversityatthe2018annualMRAretreat.Earlydetectionsaveslives,giventhe95%ten-yearsurvivalrateforpatientsdiagnosedwithveryearlystagemelanoma.3However,thatinkishardtoread.Therearevariousvisualcluesthatcanindicateacancerousskinlesion,butnotallcancerousmolessharethesefeaturesandharmlessmolescansometimeshavesimilarclinicalfeatures.It’seasytounderstandwhymisdiagnosishappens.

Thatmaysoonchange,giventhepromisingresultsofanewcomputer-basedsystemfordistinguishingmalignantfrombenignmolesorothernon-cancerousskinconditions,suchaspsoriasis.Withtheadventofartificialintelligencecombinedwithlarge

imagedatabasesand“deeplearning”algorithms,SwetterandherStanfordDermatologyandComputerSciencecolleagueswereinspiredtocreateacomputerprogramthatcouldlearntherelevantpatternsofvariousskinconditionsandaidthediagnosisofearlymelanoma.“Wefiguredifartificialintelligencecandifferentiatebetweenhundredsofdogbreedsinpictures,itcouldmakeagreatcontributiontodermatology,”Swettersaid.

Initialresultsofthesystemtheresearcherscreatedarepromising.Afterbeingtrainedonadatabaseofnearly130,000imagesspanningthebreadthofskindiseases,thesystemperformedatleastaswellas21board-certifieddermatologistsindistinguishingskinmelanomasfrombenignmoles.“Thisisanastoundingresultthatacomputersystemtrainedoveramatterofweekscouldoutperformhumanexpertswhohadspentyearsintraining,”Swettersaid,addingthatovertimeasthecomputersystemcontinueslearning,itsdiagnosticperformanceisalsolikely toimprove.

Butmoretestsneedtobedonetoverifytheaccuracyofthesystem.Swetterexpectsthecomputerprogramtobereadyforlarge-scaleclinicaltestswithinanotheryear,includinganappversionthatcanbeusedonasmartphone.Thisappmayalsoenableearlydetectionofmelanomaandotherskincancersinremote,underservedpopulations,Swetternoted.Butneithertheappnorcomputerprogramarereadyformolesurveillance,sincetheydon’tyetlookatsequentialchangesinmoles,Swettersaid.

Shestressedthatartificialintelligencesystems,suchastheoneshehelpedtocreate,aredecisionsupporttoolsandwon’treplacedermatologistsinthediagnosisofmelanoma.Butsheadded“IfAIcanbedemonstratedtoperformrobustlyinprospectiveclinicalsettings,Iamwillingtoincorporateitsresultsintomymedicaldecision-making.”Shegaveanexampleofanimageofapatient’smolewhosefeatureswereambiguousenoughthatherresearchcolleaguewasonthefenceaboutwhethertobiopsyit.“Ourcomputersystemweighedinonthesideofmalignancy(asdidtheclinician),andlowandbeholditwasasubtleearlymelanoma,sotheproofisinthepudding,”Swettersaid.

APPLYING ARTIFICIAL INTELLIGENCE TO MELANOMA DETECTION

Susan Swetter

3https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage.html

14

ThereisnodoubtthattreatmentsformetastaticmelanomahavechangeddramaticallyinthedecadesinceMRA’sfoundingin2007.Targetedtherapyandimmunotherapyhavebecomemainstaysoftreatmentandhaveextendedpatientlives.Inaddition,newapproachestothediagnosticworkupforpatientshavebeenrecentlyannouncedandmultipletreatmentstokeepmelanomafromreturningaftersurgeryarenowavailable.Specifically:

• Eleventreatments4forpatientswithmetastaticmelanomagarneredFDAapprovalsince2011including:a)targeteddrugsforBRAFandMEK;and,b)immunotherapywithcheckpointblockade,cytokinesoroncolyticviraltherapy.Over400melanomainterventionaltrialsarerecruitingpatientsonwww.clinicaltrials.gov,5

• Treatmentcontinuestoevolvewiththelate2017approvalofnivolumabformelanomaadjuvanttherapy,theApril30,2018,approvalofadjuvantdabrafenibandtrametinib,andencouragingdataforotherdrugs,6

• Newmelanomastagingguidelinesandrecommendationsoncompletelymphnodedissection(CLND)haverecentlybeenpublished,7,8

• Companiondiagnostics9forbothtargetedandimmunotherapyhavegainedapprovalandbiomarkerdevelopmentremainsatoppriority.

Thesechangesinthestandardofcareformelanomabringwiththemtheneedtoconsiderwhattheirimpactisonhowevennewertreatmentsaredevelopedfromthestandpointofacademicandgovernmentresearchers,biopharmascientistsandregulators.

Over50thoughtleaderscametogetheratanannual,invitation-onlyIndustryRoundtabletoidentifyanddiscusscross-cuttingissuesfacingmelanomatreatmentanddiagnosticdevelopment.Participantsincludedrepresentativesfromacademia,FDA,

industry,NCIandMRA.ThesessionwasmoderatedbyDr.Antoni(Toni)RibasandMRAChiefScienceOfficer,Dr.LouisePerkins.Amongthetopicsdiscussedwerea)clinicaltrials;b)endpoints;and,c)biomarkers.

Ribasaskedaprovocativequestiontokickoffdiscussion,“Aretheretoomanyclinicaltrialsbeingconductedinmelanoma?”Giventheneedforimprovedoutcomesandtherationalesupportingmosttrials,theoverwhelmingmajorityofparticipantsfeltthattheanswerwasaresounding“No,therearenottoomanytrials.”Whatfollowedwasanuanceddiscussionthatexploredbothefficiencyimprovementsandmobilizingthepreciousresourceofpatientswhoareableandwillingtoparticipateinsuchtrials.MRA,alongwithexternalpartners,recentlylaunchedMelanoma>Exchange tobolstereducationaboutclinicaltrialsandanonlineplatformthatmakesiteasierforpatientstofindatrial.

Onewaytoimprovetheefficiencyofmelanomaclinicaltrialswouldbethedevelopmentofendpointstomoreaccuratelypredictwhethertreatmentsareworkingascomparedtothoseincommonusetoday.Forexample,tumorshrinkage,progressionaftertreatmentandoverallsurvivalarecommonendpoints.Butwhatifabloodtest,animagingendpointorapathologymeasurementcouldaccuratelyshedlightonwhetheryourtreatmentisworkingorisfailingearlierthancurrenttechnologiescandetermine?Thereisgreatinterestinthisareaanditspotentialtomorerapidlyandaccuratelyinformdrugdevelopment.

Biomarkerdevelopmentisarelatedsubjectthatattemptstomeasurethingslikeproteinsorcelltypestohelpidentifywhichpatientswillbenefitfromwhichtreatment.Agreatdealofeffortinresearchisbeinginvestedtodevelopthesebiomarkersformelanomaandtousethemtoidentifywhichpatientsareinneedofmoreaggressiveorearliertherapycomparedtothosewhowilldofinewithstandardsurgeryorexistingdrugs.

Anothertopicthatwasdiscussedrelatedtobringingpotentiallylife-savingtreatmentstopatientsmorequicklybyincludingpatientsintrialswhoaretypicallyexcluded.Forexample,patientswithbrainmetastaseshavehistoricallybeenexcludedfromclinicaltrialseventhougharound15%ofnewlydiagnosedmelanomapatientshaveexistingbrainmets.Recentworkbyamulti-stakeholdergroupmadethecaseformodernizingclinicaltrialeligibility,includingtreatingcertainpatientswithbrainmets,10toachieveseveralobjectivesincludingunderstandingthesafetyandefficacyinreal-worldpopulationsandalsotopotentiallyenrollmorepatientsontrialsmorequickly.

Inconclusion,therapidityofchangeinmelanomasincethefirstwaveofnewtreatmentscametomarketin2011hasbeenastounding.ThroughdialogueamongexpertssuchasatthisIndustryRoundtable,problemsandsolutionscanemergethataddressproblemsthatnowexistduetotherelativesuccessin thefield.

MAINTAINING THE PACE OF MELANOMA INNOVATION IN THE ERA OF AN EVOLVING STANDARD OF CARE

Louise Perkins and Antoni Ribas

4https://www.curemelanoma.org/about-mra/mra-overview/5 https://clinicaltrials.gov/ct2/results?cond=melanoma&Search=Apply&recrs=a&age_v=&gndr=&type=Intr&rslt6https://www.uptodate.com/contents/adjuvant-therapy-for-cutaneous-melanoma#H934565933&https://www.novartis.com/news/media-releases/novartis-combination-adjuvant-therapy-tafinlarr-mekinistr-receives-fda

7 http://onlinelibrary.wiley.com/doi/10.3322/caac.21409/full8 https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf

9https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm

10 http://ascopubs.org/doi/full/10.1200/JCO.2017.74.0761

15

AGENDA

16

Wednesday, February 28th 1:30-5:30 pm Melanoma Advocates & Foundations Forum (invitation only)……………………….………Salon II

4:00-8:00pm Registrationopen……………………….…………………………………………….……..FoyerofSalonIII

6:00-7:30 pm Opening Reception………………………………………………………….…...……………….... Salon III

Thursday, March 1st6:30am-6:00pm Registration..…………………………………………………………...........…..OutsideofSalonBallroom7:00-8:15am GeneralBreakfast…………………………………..…………………………………………………SalonIII7:00-8:15am YoungInvestigatorsBreakfast(byinvitationonly)……………………..………....……….PlazaBallroom8:30-8:45 am Opening Remarks Day 1……………………………………………………………………….Salon I & II MichaelKaplan,MRAPresident&CEO LouisePerkins,MRAChiefScienceOfficer SamanthaStinchcomb,WayneStinchcombBigOrangeFoundation

8:45-9:15 am Lecture Suzanne Topalian, Johns Hopkins University: A decade of progress in melanoma

9:15-11:10 am Session 1: New approaches and tools for predicting efficacy: immunotherapy and beyond Chair:JenniferWargo9:15-9:40 Kai Wucherpfennig, Dana-Farber Cancer Institute:Humananti-MICAmonoclonalantibodiesfor

melanomaimmunotherapy9:40-10:05 Marisol Soengas, Spanish National Cancer Research Center (CNIO):Imagingandtargeting

dormantandpro-metastaticmelanomalesionsinvivo10:05-10:25 Iwei Yeh, University of California, San Francisco:Activatingß-cateninmutationscooperatewith

BRAFV600Etopromoteinvasion10:25-10:45am Break10:45-11:10 Yvonne Saenger, Columbia University:Combinationimmunotherapyleadstodecreasedtumor

growth,improvedsurvivalandintratumoralimmuneinfiltrationintransgenicmurinemodelofmelanoma

11:10 am-12:00 pm Session 2: Microbial influences on immunotherapy efficacy Chair:MarisolSoengas

11:10-11:35 Tom Gajewski, University of Chicago:Thecommensalmicrobiotaasanewvariableimpactingcancerimmunotherapy

11:35-12:00 Jennifer Wargo, MD Anderson Cancer Center:Profilingthemicrobiometopredictimmunotherapyefficacy

AGENDA

17

12:00-12:10pm Transitiontolunch12:10-1:15pm Lunch and Panel Discussion………………………..……………………….…….....….....….... Salon III The changing landscape of melanoma Moderator:ElliottSigal,MRABoardofDirectors

Panelist:RichardPazdur,OncologyCenterofExcellence,FDA Panelist:MarcTheoret,OncologyCenterofExcellence,FDA Panelist:NageatteIbrahim,Merck Panelist:DavidFeltquate,Bristol-MyersSquibb Panelist:CarolineRobert,InstitutGustaveRoussy1:15-1:30pm Transitiontoroom

1:30-3:00 pm Session 3: Melanoma metastasis……………………………..………………….……….…. Salon I & II

Chair:RobertVonderheide1:30-1:55 Michael Davies, MD Anderson Cancer Center:TargetingBRAFmutantbrainmetastases1:55-2:15 Manuel Valiente, Spanish National Cancer Research Center (CNIO):Blockingbrainmetastasis

bytargetingthemicroenvironment2:15-2:35 Lucia Jilaveanu, Yale University:ResponsetoPD-1inhibitorsinmelanomapatientswithbrain

metastases2:35-3:00 Robert Vonderheide, University of Pennsylvania:Radiationandimmunecheckpointblockade

frommechanismtopatients3:00-3:20pm Break3:20-5:00 pm Session 4: New targets for melanoma…………………………………………………….….Salon I & II Chair:IdoAmit

3:20-3:45 F. Stephen Hodi, Dana-Farber Cancer Institute:CombinedCTLA-4andangiopoietin-2blockadeinadvancedmelanomapatients

3:45-4:05 Niroshana Anandasabapathy, Weill Cornell Medical School:Tissueimmunedifferentiationrevealsnewpathwaysofmelanomaescape

4:05-4:30 Michal Lotem, Hadassah Medical Organization:MechanismofactionofSLAMF6anditspotentialroleinimmunotherapy

4:30-4:55 Ido Amit, Weizmann Institute of Science:Singlecellanalysisandperturbationofthetumor-immuneecosystem

4:55-5:00 Closing Remarks Day 1 KristenMueller,MRAScientificProgramDirector

6:30-9:00 pm Reception and Dinner…………………………………………..………..………Teddy & the Bully Bar* Dress:Casual120019thStreet,NW,(202)872-8700 Reception:6:30-7:00pm;Dinner:7:15pm*6:15-7:00pm:TransportationprovidedtoTeddy&BullyBar;Shuttleswilldepartfromthecirculardriveoutsidethehotellobby.Uponexitingthehotel,beartoyourrightandshuttleswillbestationedinthebreezewaybetweenthehotelandartgalleryontheproperty.

18

Friday, March 2nd6:30-10:00am Registrationopen……………………………………………………....…OutsideSalonBallroom7:00-8:30am GeneralBreakfast……………………………………………………………..…………….SalonIII7:00-8:30am IndustryRoundtableBreakfast(byinvitationonly)………………………....…...PlazaBallroom8:40-8:45 am Opening Remarks Day 2 ……………………………………………………………...Salon I & II KristenMueller,MRAScientificProgramDirector8:45-11:25 am Session 5: New strategies in preventing and treating melanoma Chair:LewisCantley8:45-9:10 Georgina Long, Melanoma Institute Australia, University of Sydney:Adjuvanttherapy

formelanoma9:10-9:30 Steve Barthel, Brigham and Women’s Hospital:Melanomacell-intrinsicTim-3:An

unexpectedvariableincancerimmunotherapy?9:30-9:50 Amanda Lund, Oregon Health & Science University:LymphaticvesselsandT

cell-inflammationinmelanoma9:50-10:15 Boris Bastian, University of California, San Francisco:Structureandexpression

levelofBRAFfusionkinasesaffectdrugresponse10:15-10:35am Break10:35-11:00 Susan Swetter, Stanford University:Artificialintelligence(AI)forcutaneous

melanomadetection11:00-11:25 Emily Bernstein, Icahn School of Medicine at Mount Sinai:Harnessingtheepigenome

formelanomaoncogenediscovery11:25-11:55 Lecture Lewis Cantley, Weill Cornell Medical School:DevelopmentofAMPKactivatorsfor

treatmentofmelanoma

11:55-12:35pm Panel Discussion

A decade of MRA: Funding for the future Moderator:MargaretAnderson,MRABoardofDirectors Panelist:DebraBlack,MRABoardChairandCo-founder Panelist:GeorginaLong,MelanomaInstituteAustralia,UniversityofSydney Panelist:RichardMarais,CancerResearchUKManchesterInstitute Panelist:SuzanneTopalian,JohnsHopkinsUniversity,MRABoardofDirectors Panelist:JeddWolchok,MemorialSloanKetteringCancerCenter

12:35-12:45 pm Closing Remarks

MichaelKaplan,MRAPresidentandCEO LouisePerkins,MRAChiefScienceOfficer

12:45-2:00 pm Lunch and Departures…………………………………………………………………Salon III

19

Sama Ahsan Clinical Director Merck & Co., Inc. sama.ahsan@merck.com

Alexandre Alencar Program Manager Rising Tide Foundation for Clinical Cancer Research alexandre.alencar@risingtide.ch

Ido Amit Professor Weizmann Institute of Science ido.amit@weizmann.ac.il

Niroshana Anandapathy Attending Physician, Assistant Professor Weill Cornell Medicine niroananda@gmail.com

Ana AndersonAssociate ProfessorHarvard Medical Schoolaanderson@bwh.harvard.edu

Margaret AndersonBoard Member, MRAManaging DirectorDeloitte

Steve AnrederPresident & CEOAnreder & Companysteven.anreder@anreder.com

Andrew AplinAssociate DirectorThomas Jefferson Universityandrew.aplin@jefferson.edu

Charlotte AriyanAssociate AttendingMSKCCariyanc@mskcc.org

Julia ArnoldProgram DirectorNIH/NCIjarnold@mail.nih.gov

Maryam AsgariAssociate ProfessorMassachusetts General Hospitalmasgari@partners.org

Michael AtkinsDeputy DirectorGeorgetown Lombardi Cancer Centermba41@georgetown.edu

Alex AvilaIO Medical Lead, GU and MelanomaBristol-Myers Squibbalexandre.avila@bms.com

Anand BalasubramaniAssociate EditorScience Immunologyabalasubramani@aaas.org

Cody BarnettDirector of CommunicationsMelanoma Research Alliancecbarnett@curemelanoma.org

Steven BarthelInstructorBrigham & Women’s Hospitalsbarthel@rics.bwh.harvard.edu

Boris Bastian Professor UCSF boris.bastian@ucsf.eduEmily BernsteinAssociate ProfessorIcahn School of Medicine at Mount Sinaiemily.bernstein@mssm.edu

Nina BhardwajDirector of ImmunotherapyIcahn School of Medicine at Mount Sinainina.bhardwaj@mssm.eduJohn BigganePresidentMollie Biggane Melanoma Foundationbigganej@optonline.netMaggie BigganePresidentMollie Biggane Melanoma Foundationbigganem@optonline.netBenjamin BlackBoard Member, MRAVice PresidentOCV PartnersDebra BlackCo-Founder & Chair, MRABroadway ProducerLeon BlackCo-Founder, MRAChairman & CEOApollo Global Management, LLC

Christian BlankMolecular Oncology & ImmunologyNetherlands Cancer Institutec.blank@nki.nl

PARTICIPANTS

Michael Kaplan

20

Kim BlenmanAssociate Research ScientistYale Universitykim.blenman@yale.edu

Paul BlieseDirector of PhotographyCreative Services, Milken Institutepbliese@mff.orgAlexander BoikoAssistant ProfessorUC Irvineaboiko@uci.eduIvan BorrelloAssociate Professor of OncologyJohns Hopkins Universityiborrell@jhmi.eduMarcus BosenbergProfessor of Dermatology and PathologyYale Universitymarcus.bosenberg@yale.eduStephen BrodyPartnerO’Melveny & Myers LLPsbrody@omm.com

Peter BrossOncology Branch Team LeadUS/FDA/CBER/OTATpeter.bross@fda.hhs.govSubira BrownDevelopment AssociateMelanoma Research Alliancesbrown@curemelanoma.orgTyler BrownPatient Engagement & Operations AssociateMelanoma Research Alliancetbrown@curemelanoma.orgTimothy BullockAssociate Professor, Immune Therapy CenterUniversity of Virginiatb5v@virginia.eduChristin BurdAssistant ProfessorOhio Stateburd.25@osu.eduTal Burstyn-CohenPrincipal InvestigatorThe Hebrew University of Jerusalemtalbu@ekmd.huji.ac.il

Lisa ButterfieldProfessor of Medicine, Surgery and ImmunologyUniversity of Pittsburghbutterfieldl@upmc.eduKatherine ByrnesExecutive DirectorSkin of Steelkbyrnes@skinofsteel.orgLewis CantleyProfessorCornelllcantley@med.cornell.eduJoseph CantorAssistant ProfessorUCSDjmcantor@ucsd.eduTanisha CarinoExecutive DirectorFasterCurestcarino@fastercures.orgRichard CarvajalAssociate Professor of MedicineColumbia University Medical Centerrdc2150@cumc.columbia.edu

Nageatte Ibrahim, David Feltquate, Marc Theoret, Richard Pazdur, Caroline Robert, Elliott Sigal

21

Jonathan CebonMedical DirectorOlivia Newton-John Cancer Research Institutejonathan.cebon@onjcri.org.auPaul ChapmanAttending PhysicianMSKCCchapmanp@mskcc.orgSidi ChenAssistant ProfessorYale Universitysidi.chen@yale.eduXu ChenAssistant ProfessorUCSFxu.chen@ucsf.eduVictoria ChiouMedical OfficerFDAvictoria.chiou@fda.hhs.govRadha ChitaleDigital EditorInspireradha@inspire.comKierstyn ClaycombDirector, Business DevelopmentNewLink Geneticskclaycomb@linkp.comDavid CohanMedical DirectorAmgen, Inc.dcohan@amgen.com

Sara CulverMarketingLoxo Oncologysculver@loxooncology.comEllie DanielsProgram DirectorAmerican Cancer Societyellie.daniels@cancer.orgPaul DanielsenManaging DirectorSolCarib BZpdanielsen@mindspring.comMichael DaviesAssociate ProfessorMD Anderson Cancer Centermdavies@mdanderson.orgEllen DavisBoard Member, MRAPrincipalMakana BeveragesScott DiedeSenior Clinical DirectorMerck & Co., Inc.scott.diede@merck.comLaura DimmittMedical Affairs-Advocacy ManagerProvectus Biopharmaceuticalsldimmitt@pvct.comJohn D’OrazioProfessor of PediatricsUniversity of Kentuckyjdorazio@uky.eduLeslie DorosMedical OfficerFDAleslie.doros@fda.hhs.govStephanie DouganAssistant ProfessorDana-Farber Cancer Institutestephanie_dougan@dfci.harvard.eduClaudia DuludeCEODefeat Melanomaclaudia.dulude@gmail.com

Shelton EarpDirectorUNC Lineberger Comprehensive Cancer Centershelton_earp@med.unc.eduNeta ErezLab Head, Department ChairTel Aviv Universitynetaerez@post.tau.ac.ilAnna Marie FarroPresidentMoving for Melanoma of DEannamom1@aol.comBenson FayehunMarketing DirectorMerckbenson.fayehun@merck.comDavid FeltquateHead of Early Clinical DevelopmentBristol-Myers Squibbdavid.feltquate@bms.comTeri FestaExecutive DirectorLive SunSmart Foundationteri@rayfesta.orgDavid FisherChief of DermatologyMassachusetts General Hospitaldfisher3@partners.orgKeith FlahertyDirector of Developmental TherapeuticsMassachusetts General Hospitalkflaherty@mgh.harvard.eduOlivia FlattoExecutive DirectorPershing Square Sohn Cancer Research Allianceotflatto@persq.orgElaine FuchsRebecca C. Lancefield ProfessorThe Rockefeller Universityfuchs@mail.rockefeller.edu

PARTICIPANTS

Benjamin Black and Xu Wu

22

Thomas GajewskiProfessorUniversity of Chicagotgajewsk@medicine.bsd.uchicago.eduChristine GarrisonPresidentThe White Aisle Foundationthewhiteaisle@comcast.netWayne GarrisonBoard MemberThe White Aisle Foundationwmgarrison@comcast.netEvripidis GavathiotisAssociate ProfessorAlbert Einstein College of Medicineevripidis.gavathiotis@einstein.yu.eduRachel GazzerroAssociate Director, Development& Information ManagementMelanoma Research Alliancergazzerro@curemelanoma.orgJeffrey GershenwaldProfessorThe University of Texas MD Anderson Cancer Centerjgershen@mdanderson.orgMichael GoldbergAssistant ProfessorDana-Farber Cancer Institutemichael_goldberg1@dfci.harvard.eduMark GormanPatient AdvocateLee GrinbergPortfolio ManagerElliott Managementlgrinberg@elliottmgmt.comMeyer GrinbergVolunteerMelanoma Research Alliancemeyergrinberg@gmail.comValerie GuildPresidentAIM at Melanomavguild@aimatmelanoma.org

Piyush GuptaAssociate ProfessorWhitehead Institute/MITpgupta@wi.mit.eduRuth HalabanSenior Research ScientistYale Universityruth.halaban@yale.eduAllan HalpernMemberMSKCChalperna@mskcc.orgOmid HamidDir, Melanoma Oncology; Chief, Clinical ResearchThe Angeles Clinic and Research Instituteohamid@theangelesclinic.orgBrent HanksAssistant ProfessorDuke Universitybrent.hanks@duke.eduRizwan HaqAssistant ProfessorDana-Farber Cancer InstituteRizwan_Haq@dfci.harvard.eduBill HarbourDirector, Ocular OncologyVice Chairman, TranslatUniversity of Miamiharbour@miami.eduMaitreyee HazarikaSenior Medical OfficerFDAmaitreyee.hazarika@fda.hhs.govMeenhard HerlynProfessor and Program DirectorThe Wistar Instituteherlynm@wistar.orgEva HernandoAssociate ProfessorNew York University Medical Centereva.hernando-monge@nyumc.org

Jack HidaryChairmanSarcos Roboticsjackhidary@gmail.comPing-Chih HoAssistant ProfessorUniversity of Lausanne/Ludwig Lausanne Branchping-chih.ho@unil.chF. Stephen HodiDirector, Melanoma Disease Center & Center for Immuno-OncologyDana-Farber Cancer Institutestephen_hodi@dfci.harvard.eduSheri HolmenProfessorUniversity of Utahsheri.holmen@hci.utah.eduDavid HoonDirectorJohn Wayne Cancer Institutehoond@jwci.orgThomas HornyakAssociate Chief of Staff for Research & Development , VA Maryland Health Care SystemUniversity of Maryland/VAthomas.hornyak@va.govWilly HugoAssistant Adjunct ProfessorUCLAhwilly@mednet.ucla.eduSiwen Hu-LieskovanAssistant Professor of MedicineUCLAshu-lieskovan@mednet.ucla.eduNick HuntingtonImmunotherapy HeadWEHIhuntington@wehi.edu.auPatrick HwuHead, Division of Cancer MedicineUTMDACCphwu@mdanderson.org

23

Nageatte IbrahimExecutive Director, Clinical Research, MelanomaMerck & Co., Inc.nageatte.ibrahim@merck.comRamy IbrahimVP Clinical DevelopmentParker Institute for Cancer Immunotherapyribrahim@parkerici.orgFumito ItoAssociate Professor of SurgeryRoswell Park Cancer Institutefumito.ito@roswellpark.org

Burkhard JansenChief Medical OfficerDermtechbjansen@dermtech.comLucia JilaveanuAssistant ProfessorYale Universitylucia.jilaveanu@yale.eduDoug JohnsonAssistant Professor of MedicineVanderbilt Universitydouglas.b.johnson@vanderbilt.edu

Barinder KangExecutive Director Clinical StrategyNovartisbarinder.kang@novartis.comMichael KaplanPresident & CEOMelanoma Research Alliancemkaplan@curemelanoma.orgFlorian KarrethAssistant MemberMoffitt Cancer CenterFlorian.Karreth@moffitt.org

Tibor KelerExecutive VP & CSOCelldex Therapeutics, Inc.tkeler@celldex.comPriscilla KellyEditorAAAS/Sciencepkelly@aaas.orgJohn KirkwoodUsher Professor of Medicine, Dermatology,and Translational ScienceUPMC Hillman Cancer Centerkirkwoodjm@upmc.edu

Libby KistlerFounderKistler & Co.opkva117@gmail.comMichael KlowdenBoard Member, MRAChief Executive OfficerMilken InstituteDavid KnorrClinical ScholarRockefeller Universitydknorr@mail.rockefeller.eduSebastian KoboldAttending Physician, Assistant ProfessorKlinikum der Universität Münchensebastian.kobold@med.uni-muenchen.deMiguel KorteExecutive Director, Medical Affairs/IML OGMAMerck & Co., Inc.miguel.korte@merck.comMichael KrauthammerAssociate ProfessorYale Universitymichael.krauthammer@yale.eduClemens KreplerDirector, Clinical ResearchMerck & Co., Inc.clemens.krepler@merck.comArt KriegChief Executive OfficerCheckmate Pharmaceuticalsakrieg@checkmatepharma.comAshish KulkarniAssistant ProfessorUniversity of Massachusetts Amherstakulkarni@engin.umass.eduRajan KulkarniAssistant ProfessorUCLArkulkarn@ucla.edu

PARTICIPANTS

David Cohen

24

Trip LaneBoard MemberSkin of Steeltriplane23@sbcglobal.netBenjamin LarimerInstructorMassachusetts General HospitalBLARIMER@mgh.harvard.eduSancy LeachmanProfessor & Chair, Department of DermatologyOregon Health & Science Universityleachmas@ohsu.eduJeff LegosSenior VP & Franchise HeadNovartisjeff.legos@novartis.comSteven LemeryAssociate Division Directory, DOP2FDAsteven.lemery@fda.hhs.govEvan LipsonAssistant Professor, Medical OncologyJohns Hopkins Universityelipson2@jhmi.eduFeng Liu-SmithAssistant ProfessorUC Irvineliufe@uci.eduRoger LoProfessor & Attending PhysicianUCLArlo@mednet.ucla.eduDavid LombardAssociate Professor of PathologyUniversity of Michigandavidlom@umich.eduGeorgina LongConjoint Medical DirectorMelanoma Institute Australia,The University of Sydneygeorgina.long@sydney.edu.au

A. Thomas LookPrincipal Investigator/Professor of PediatricsDana-Farber Cancer Institutethomas_look@dfci.harvard.eduMichal LotemHead, Center for MelanomaHadassah Medical Centermlotem@hadassah.org.ilJason LukeAssistant Professor of MedicineUniversity of Chicagojluke@medicine.bsd.uchicago.eduAmanda LundAssistant ProfessorOregon Health & Science Universitylunda@ohsu.eduRichard MaraisDirectorCancer Research UK Manchester Instituterichard.marais@cruk.manchester.ac.ukKim MargolinClinical ProfessorCity of Hope National Medical Centerkmargolin@coh.orgSabran MasoudSchool of MedicineDuke Universitysabran.masoud@duke.eduMark McLaughlinProfessorWest Virginia Universitymark.mclaughlin@hsc.wvu.eduMartin McMahonHuntsman Cancer Institute & Dept. of DermatologyUniversity of Utahmartin.mcmahon@hci.utah.eduJanice MehnertRegional Phase I Clinical Program Director; Medical OncologistRutgers Cancer Institutemehnerja@cinj.rutgers.edu

Thorsten MempelAssociate ProfessorMassachusetts General Hospitaltmempel@mgh.harvard.eduDebbie MercierDirector, Medical AffairsNewLink GeneticsDMercier@linkp.comGlenn MerlinoScientific Director for Basic ResearchDHHS/NIH/NCI/CCRgmerlino@helix.nih.govMartin MihmProfessor, Pathology and DermatologyBrigham & Women’s Hospitalmartin.mihm@bwh.harvard.eduDebbie MillerCo-FounderTara Miller Melanoma Foundationdmiller8375@gmail.comGeorge MillerCo-FounderTara Miller Melanoma Foundationgmiller@gmillerlawfirm.comKristi MillerCo-FounderTara Miller Melanoma Foundationkam609@gmail.comLauren MillerCo-FounderTara Miller Melanoma Foundationlmiller1127@gmail.comNicholas MitsiadesAssociate ProfessorBaylor College of Medicinemitsiade@bcm.eduJoao MonteiroEditor-in-ChiefNature Medicinejpdaher@gmail.com

25

Federico MonzonChief Medical OfficerCastle Biosciencesfmonzon@castlebiosciences.comJames MoonJohn Gideon Searle Assistant ProfessorUniversity of Michiganmoonjj@umich.eduEduardo Gerardo MorosChief of Medical PhysicsH. Lee Moffitt Cancer Center& Research Instituteeduardo.moros@moffitt.orgAaron MorrisSenior Director, ResearchCheckmate Pharmaceuticalsamorris@checkmatepharma.comDavid MorseAssociate MemberH. Lee Moffitt Cancer Center & Research Institutedavid.morse@moffitt.orgRebecca MossClinical Program Lead, MelanomaBristol-Myers Squibbrebecca.moss@bms.comKristen MuellerScientific Program DirectorMelanoma Research Alliancekmueller@curemelanoma.orgKatherine NathansonProfessor, Dept. of Medicine, Translational Medicine & Human GeneticsUniversity of Pennsylvaniaknathans@upenn.eduKimberly NoonanChief Science OfficerWindMIL Therapeutics, Incnoonan@windmiltherapeutics.comYevgeniya NusinovichSenior EditorScience Translational Medicine/AAASynusinov@aaas.org

Christy OsgoodMedical OfficerFDAchristy.osgood@fda.hhs.govPatrick OttClinical DirectorDana Farber Cancer InstitutePatrick_Ott@DFCI.harvard.eduWillem OverwijkProfessorMD Anderson Cancer Centerwoverwijk@mdanderson.orgFan PanAssociate ProfessorJohns Hopkins Universityfpan1@jhmi.eduSarthak PanditAdvocacy & Professional AffairsMerck & Co., Inc.Sarthak.pandit@merck.comDrew PardollProfessor of Oncology, Director Cancer ImmunologyJohns Hopkins Universitydpardol1@jhmi.eduFrances PascavageMedical Marketing, OncologyNovartisfrances.pascavage@novartis.comSapna PatelPhysicianMD Anderson Cancer CenterSPPatel@mdanderson.orgMargie PatlakScience WriterMargie Patlak Inc.margiepatlak@gmail.comElizabeth PattonProgramme Leader and ReaderMRC Human Genetics Unit,The University of Edinburghliz.patton@igmm.ed.ac.uk

Anna PavlickProfessor of Medicine and DermatologyNYU Cancer Centeranna.pavlick@nyumc.orgRichard PazdurDirector, Office of Oncology Drugs ProductFDArichard.pazdur@fda.hhs.govGuangyong PengProfessorSaint Louis Universitygpeng@slu.eduLouise PerkinsChief Science OfficerMelanoma Research Alliancelperkins@curemelanoma.orgDavid PolskyProfessorNYU Langone Healthdavid.polsky@nyumc.orgCatherine M. PoolePresident & FounderMelanoma International Foundationcpoole@melanomainternational.orgPoulikos PoulikakosAssistant ProfessorIcahn School of Medicine at Mount Sinaipoulikos.poulikakos@mssm.eduHelen PowellMD/MPH studentUNC-Chapel Hill School of Medicinehelen_powell@med.unc.eduChristine PratilasAssistant ProfessorJohns Hopkins Universitycpratil1@jhmi.eduTasheema PrinceScientific Program ManagerMelanoma Research Alliancetprince@curemelanoma.org

PARTICIPANTS

26

Raj PuriDivision Director of Cellular and Gene TherapyFDAraj.puri@fda.hhs.govCharles PuzaDuke Universitycharles.puza@duke.eduShah RahimianMedical DirectorIdera Pharmaceuticalssrahimian@iderapharma.comKunail RaiAssistant ProfessorMD Anderson Cancer Centerkrai@mdanderson.orgJon RetzlaffChief Policy Officer, & VP, Science Policy & Government AffairsAACRjon.retzlaff@aacr.orgAntoni RibasProfessor of MedicineUCLAaribas@mednet.ucla.eduMaryLisabeth RichVP Principal PartnershipsAmerican Cancer Societymarylis.rich@cancer.org

David RicklesChief Scientific OfficerRadimmune Therapeuticsdrickles@radimmune.comTodd RidkyAssistant ProfessorUniversity of Pennsylvaniaridky@pennmedicine.upenn.eduCaitlin RileyPatient Advocatecrileyri@gmail.comCorey RitchingsAssociate Director, Immuno-Oncology Medical ScientistBristol-Myers Squibbcorey.ritchings@bms.com

Rocio RiveraScientific Communications DirectorL’Oréal Paris, USACaroline RobertHead of Dermatology UnitGustave Roussycaroline.robert@gustaveroussy.frMary Jo RogersBoard Member, MRAZe’ev RonaiCo-Director, TICCTechnicon Israel Institute of Technologyronai@technion.ac.ilNeal RosenMember, Dept. of Medicine and MPCMemorial Sloan-Kettering Cancer Centerrosenn@mskcc.orgSteven RosenbergChief, Surgery BranchNational Cancer Institutesar@nih.govJeffrey RowbottomBoard Member, MRAManaging DirectorPSP Investments USAAlicia RowellVice-PresidentAIM at Melanomaalicia@aimatmelanoma.orgMichael RowinskiDirectorBristol-Myers Squibbmichael.rowinski@bms.comMark RubinsteinAssistant ProfessorThe Medical University of South Carolinamarkrubinstein@musc.eduSelena RushSenior Director Medical Affairs OperationsArray BioPharma Inc.Selena.Rush@arraybiopharma.com

Joan RussoChief Development OfficerMelanoma Research Alliancejrusso@curemelanoma.orgYvonne SaengerDirector, Melanoma ImmunotherapyColumbia Universityyms4@cumc.columbia.eduChristine SamsSpokespersonMitsy’s Wingschristinesams29@hotmail.comYardena SamuelsAssociate ProfessorWeizmann Institute of Scienceyardena.samuels@weizmann.ac.ilNeville SanjanaCore Faculty MemberNew York Genome Center & NYUnsanjana@nygenome.orgRonit Satchi-FainaroChair, Department of Physiology and PharmacologyTel Aviv Universityronitsf@tauex.tau.ac.ilLynn SchuchterChief, Hematology/Oncology DivisionUniveristy of Pennsylvanialynn.schuchter@uphs.upenn.eduGary SchwartzChief, Hematology and OncologyColumbia Universityschwartzg@columbia.eduAmanda ScofieldHQ Medical Lead, Adjuvant MelanomaBristol-Myers Squibbamanda.scofield@bms.comMark ShackletonDirector of Oncology, Alfred HealthMonash Universitymark.shackleton@monash.edu

27

William SharfmanDirector of Cutaneous OncologyJohns Hopkins Universitysharfwi@jhmi.eduElad SharonSenior InvestigatorNational Cancer Institutesharone@mail.nih.govTJ SharpeCancer BloggerStarfish Harbor LLCpatient1@tjsharpe.comElliott SigalBoard Member, MRASenior Advisor/Venture PartnerNew Enterprise AssociatesSteve SilversteinBoard ChairMelanoma Research Foundationsttaran@aol.comLisa Simms BoothSenior Director for Patient and Public EngagementBiden Cancer Initiativelsimmsbooth@bidencancer.orgJonathan SimonsBoard Member, MRAPresident & CEOProstate Cancer FoundationAnurag SinghAssistant ProfessorBoston Universityasingh3@bu.eduCraig SlingluffProfessor of Surgery; Director, Human Immune Therapy CenterUniversity of Virginiacls8h@virginia.eduKeiran SmalleyProfessor and DirectorMoffitt Cancer Centerkeiran.smalley@moffitt.org

Jacqueline SmithPolicy and Advocacy ManagerSociety for Immunotherapy of Cancerjsmith@sitcancer.orgSusan SnodgrassExecutive DirectorIncyteSsnodgrass@incyte.comMarisol SoengasHead, Melanoma GroupSpanish National Cancer Research Centremsoengas@cnio.esDavid SolitMember, HOPP; Director, CMO; Attending Physician, Genitourinary Oncology ServiceMemorial Sloan Kettering Cancer Centersolitd@mskcc.orgMaria SosaAssistant ProfessorMount Sinaimaria.sosa@mssm.eduJeffrey SosmanDirector, Melanoma ProgramNorthwestern Universityjeffrey.sosman@nm.orgNeil SpieglerExecutive DirectorPeggy Spiegler Melanoma Research Foundationnspiegler@aol.comChloe StacyUS Oncology Advocacy PharmD FellowBristol-Myers Squibbchloe.stacy@bms.comLisa SteppExecutive Director Medical AffairsOncoSeclstepp@oncosec.com

Mark StewartSenior Science Policy AnalystFriends of Cancer Researchmstewart@focr.orgLisa StinchcombPresidentWayne Stinchcomb Big Orange Foundationlisa.stinchcomb@gdit.comSamantha StinchcombWayne Stinchcomb Big Orange Foundationsstinch@udel.eduErica StoneAssistant ProfessorThe Wistar Instituteestone@wistar.orgRyan SullivanInstructorMassachusetts General HospitalRSULLIVAN7@mgh.harvard.eduStephen SullivanBoard ChairSkin of Steelssullivan@skinofsteel.orgJohn SunwooAssociate ProfessorStanford Universitysunwoo@stanford.eduGregory SuplickNewLink Geneticsgsuplick@linkp.comSusan SwetterProfessor of Dermatology; Director, Pigmented Lesion and Melanoma Program,Stanford University, Stanford Cancer Institutesswetter@stanford.eduYuval TabachSchool of Medicine-IMRIC-Developmental Biology and Cancer ResearchHebrew Universityyuvaltab@ekmd.huji.ac.il

PARTICIPANTS

28

Mary TagliaferriSVP, Clinical Development & CMONektar TherapeuticsMTagliaferri@nektar.comJiaying TanSenior Scientific EditorCell Pressjtan@cell.comJanis TaubeDirector of DermatopathologyJohns Hopkins Hospitaljtaube1@jhmi.eduMarc TheoretAssociate Director (Acting) Immuno-Oncology TherapeuticsFDAMarc.Theoret@fda.hhs.govMargaret ThompsonMedical OfficerFDAmargaret.thompson@fda.hhs.govMagdalena ThurinProgram DirectorNIHthurinm@mail.nih.govSuzanne TopalianBoard Member, MRAProfessor of Surgery and OncologyJohns Hopkins UniversityCheryl TrockePresidentGraham’s GIftcheryl.trocke@childrensmn.orgJamie TroilPatient Advocatejtroil@yahoo.comDon UselmannPresidentMDSolarSciences duselmann@mdsolarsciences.comManuel ValienteJunior Group LeaderCNIOmvaliente@cnio.es

Navin VaradarajanAssociate ProfessorUniversity of Houstonnvaradar@central.uh.eduJessie VillanuevaAssistant ProfessorThe Wistar Institutejvillanueva@wistar.orgMaurizio VoiVP, Global Program HeadNovartisstella.joseph@novartis.comRobert VonderheideDirector, Abramson Cancer CenterUniversity of Pennsylvaniarhv@exchange.upenn.eduEric WachterChief Technology OfficerProvectus Biopharmaceuticalswachter@pvct.comKirby WalkerPatient AdvocateLi WangAssociate ProfessorMedical College of Wisconsinlilywang@mcw.edu

Ashley WardActing Clinical Team LeaderFDAashley.ward@fda.hhs.govOlivia WareVolunteerPatient Advocateware.orose@gmail.comJennifer WargoAssistant Professor, Dept. of Surgical OncologyMD Anderson Cancer Centerjwargo@mdanderson.orgKenneth WashkauMedical AffairsIncytekwashkau@incyte.comIan WatsonAssistant ProfessorMcGill Universityian.watson2@mcgill.caMichael WeberDirector Emeritus, Cancer CenterUniversity of Virginiamjw@virginia.eduAshi WeeraratnaProfessorWistar Instituteaweeraratna@wistar.org

Nicholas Huntington and Jonathan Simons

29

Fred WeinerBoard MemberPeggy Spiegler Melanoma Research Foundationfwmc28@gmail.comRichard WhiteAssistant MemberMSKCCwhiter@mskcc.orgMichael WichmanVice PresidentAnreder & Companymichael.wichman@anreder.comJoshua WilliamsPrincipal ScientistJohnson & Johnsonjwill152@ITS.JNJ.comJohn WilsonAssistant ProfessorVanderbilt Universityjohn.t.wilson@vanderbilt.eduMelissa WilsonAssistant Professor of MedicinePerlmutter Cancer Center, NYU Langone Medical Centermelissa.wilson@nyumc.org

Tara WithingtonExecutive DirectorSociety for Immunotherapy of CancerTWithington@sitcancer.orgJedd WolchokChief, Melanoma & ImmunotherapeuticsMemorial Sloan Kettering Cancer Centerwolchokj@mskcc.orgScott WoodmanAssistant ProfessorMD Anderson Cancer Centersewmdphd@yahoo.comXu WuAssociate ProfessorMassachusetts General Hospitalxwu@cbrc2.mgh.harvard.eduKai WucherpfennigProfessorDana-Farber Cancer Institutekai_wucherpfennig@dfci.harvard.eduArvin YangDevelopment Lead, Melanoma/GenitourinaryBristol-Myers Squibbarvin.yang@bms.com

Iwei YehAssistant ProfessorUCSFiwei.yeh@ucsf.eduMichael YellinVice President, Clinical ScienceCelldexmyellin@celldex.comVanshisht Yennu-NandaAssistant ProfessorM.D. Anderson Cancer Centervynanda@mdanderson.orgHassane ZarourProfessorUniversity of Pittsburghzarourhm@upmc.eduBin ZhangAssociate ProfessorNorthwestern Universitybin.zhang@northwestern.eduBin ZhengAssistant ProfessorMassachusetts General Hospitalbin.zheng@cbrc2.mgh.harvard.eduLi ZhouAssistant ScientistHenry Ford Health systemlzhou1@hfhs.orgJonathan ZippinAssistant ProfessorWeill Cornell Medicinejhzippin@med.cornell.eduLeonard ZonGrousbeck Professor of PediatricsBoston Children’s Hospitalzon@enders.tch.harvard.edu

PARTICIPANTS

Maria Soledad Sosa and Kristen Mueller

30

SPONSORSPresenting Sponsors

Platinum

Gold

Silver

Scholarship

Supporter

PMS 137c PMS 541c

BIOPHARMACEUTICALS, INC.

Melanoma Research AllianceCureMelanoma.org1101 New York Avenue, NW Suite 620Washington, DC 20005