PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
ResultsofaPhaseIITrialofSelinexor,inPa5entswith
GynaecologicalCancersIgnaceVergote1,BenteLund2,HanneHavsteen3,ZazaUjmajuridze4,ElsVanNieuwenhuysen1,CharloLeHaslund2,TrineJuhler-NøLrup4,PatrickNeven1,MortenMau-Sørensen4,PatrickBerteloot1,AnneKranich6,TamiRashal5,JulieMeade5,YosefLandesman5,GregWright5,MarshaCrochiere5,Jean-RichardSaint-Mar[n5,SharonShacham5,MichaelKauffman5,MansoorRazaMirza5
(1)KatholiekeUniversiteitLeuven,Leuven,Belgium,EuropeanUnion(2)AalborgUniversityHospital,Aalborg,Denmark(3)HerlevUniversityHospital,Herlev,Denmark(4)Rigshospitalet,UniversityofCopenhagen,Copenhagen,Denmark(5)KaryopharmTherapeu[csNewton,MA,USA(6)GSOHamburg;Germany
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
• EmploymentorLeadershipPosi5on:No
• Consultant/AdvisoryRole:No
• StockOwnership:No
• Honoraria:No
• ResearchFunding:No
• ExpertTes5mony:No
• OtherRemunera5on:No
PresenterDisclosures
2
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
Acknowledgments
• Wewouldliketothank:
– Pa[entsandtheirfamilies
– Inves[gators,co-inves[gatorsandthestudyteamsateachpar[cipa[ng
center:
• KatholiekeUniversiteitLeuven,Leuven,Belgium,EuropeanUnion
• AalborgUniversityHospital,Aalborg,Denmark
• HerlevUniversityHospital,Herlev,Denmark
• Rigshospitalet,UniversityofCopenhagen,Copenhagen,Denmark
3
ThisstudywassponsoredbyKaryopharmTherapeu[cs
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
Selinexor–MechanismofAc5on
• Expor[n1(XPO1)istheonlynuclearexporterforthemajortumorsuppressorproteins(TSPs)includingp53,p73,BRCA1andpRB
• Selinexor,afirst-in-classinhibitorofXPO1,inducesnuclearreten[on,accumula[onandac[va[onofTSPs
• Reac[va[onofTSPsleadstotumorapoptosis• Selinexorhasshownpreclinicalac[vityin-vivo
aswellasclinicalac[vityinaPhaseIstudyinovarianpa[ents(Razaket.al,JCO2016)
4
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SelinexorInGynecologicalNeoplasms(SIGN)–PhaseIIStudyDesign
• PrimaryEndpoint:
• Diseasecontrolrate(DCR)completeorpar9alresponse,orstablediseaseforatleast12weeks(SD≥12)
o Lookingfor≥8pa[entsinthefirst21pa[entsenrolledpercohorttoreachDCR,whichwillwarrantPhaseIIIexplora[on
• MainInclusionCriteria:
o Pa[ents≥18yearsold,ECOGperformancestatus0-1,Lifeexpectancy≥12weeks
o Ovarianpa[ents–Pla[numrefractory/resistantpa[ents,≥1priorchemotherapyline
o Endometrial/Cervicalpa[ents–≥1lineofchemotherapyforrelapsedoradvanceddisease
• TreatmentScheme:TwiceWeekly(BIW)orOnceWeeklyDosing(QW)/28daycycle
• 50mg/m2(BIW)• 35mg/m2(BIW)• 50mg/m2(QW)
OvarianCohort
• 50mg/m2(BIW)
EndometCohort
• 50mg/m2(BIW)
CervicalCohort
5
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SIGN–Pa5entCharacteris5cs
Characteris5c Ovarian(N=66) Endometrial(N=23) Cervical(N=25)
Pa5entsEnrolled 66 23 25
MedianAge(Range) 62years(31–80) 67years(53–75) 53years(32–75)
MedianPriorTreatmentRegimens(Range) 6(1–11) 2(1–5) 3(1–8)
PriorTreatmentsN(%)Pla5numsTaxanesAnthracyclines
66(100%)66(100%)55(83%)
22(96%)23(100%)19(83%)
25(100%)23(92%)2(8%)
6
Gastrointestinal Grade 2 Grade 3 Grade 4 Grade 2 Grade 3 Grade 4 Grade 2 Grade 3 Grade 4
Nausea 25 (34%) 9 (12%) -- 8 (38%) -- -- 10 (50%) 1 (5%) --
Vomiting 16 (22%) 6 (8%) -- 3 (14%) 1 (5%) -- 6 (30%) 1 (5%) --
Anorexia 19 (26%) 4 (6%) -- 6 (29%) 1 (5%) -- 6 (30%) -- --
Dysgeusia 8 (11%) -- -- -- -- -- 1 (5%) -- --
Diarrhea 7 (10%) 1 (1%) -- 2 (10%) -- -- 2 (10%) -- --
Dehydration -- 2 (3%) -- 3 (14%) -- -- -- -- --
Constitutional
Fatigue 31 (43%) 11 (15%) -- 7 (33%) 5 (24%) -- 6 (30%) 1 (5%) --
Weight Loss 15 (21%) -- -- 5 (24%) 1 (5%) -- -- 1 (5%) --
Blood
Thrombocytopenia 13 (18%) 17 (23%) 1 (1%) 2 (10%) 1 (5%) -- 1 (5%) -- --
Anemia 21 (29%) 8 (11%) -- 6 (29%) 2 (10%) -- 3 (15%) 1 (5%) --
Other
Hyponatremia -- 6 (8%) 1 (1%) -- 1 (5%) -- -- 2 (10%) --
AE Term
Ovarian/Endometrial/Cervical 50 mg/m2 Twice Weekly
Ovarian – 35 mg/m2 Twice Weekly
Ovarian – 50 mg/m2 Once Weekly
N=73 N=21 N=20
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SIGN–TreatmentRelatedAdverseEvents≥10%
7
• Grade3-4toxici[eswerereducedintheonceweeklydosing(50mg/m2)regimenascomparedtotwiceweeklydosing
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
PrimaryEndpoint–DiseaseControlRate(CR+PR+SD≥12Weeks)
CancerType Dose N DCR(%) PR(%)
Ovarian
35mg/m2(BIW) 18 11(61%) 2(11%)
50mg/m2(BIW) 22 10(45%) 3(14%)
50mg/m2(QW) 19 8(42%) 3(16%)
AllDoses 59 29(49%) 8(14%)
Endometrial 50mg/m2(BIW) 20 9(45%) 3(15%)
Cervical 50mg/m2(BIW) 23 6(26%) 1(4%)
ResponseswereadjudicatedaccordingtotheResponseEvalua9onCriteriainSolidTumors(RECISTv1.1)basedoninterimunauditeddata–DCR=DiseaseControlRate(CR+PR+SD≥12)
8
-80%
-60%
-40%
-20%
0%
20%
40%
60%
80%
100%
120%
Percen
tCha
nge
PecentChangeinTargetLesions
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SIGN–TumorResponse
Ovarian(N=50)
Endometrial(N=19)
Cervical(N=18)
ProgressiveDisease
Par5alResponse
CancerType Dose N PR(%) SD≥12Weeks(%)
SD<12Weeks(%) PD(%)
Ovarian AllDoses 59 8(14%) 21(36%) 4(7%) 26(44%)
Endometrial 50mg/m2(BIW) 20 3(15%) 6(30%) 3(15%) 8(40%)
Cervical 50mg/m2(BIW) 23 1(4%) 5(22%) 2(9%) 15(65%)
9
PresentedatESMOCongress2016byIgnaceVergote.
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
DCRPa5entsResponse&TimeonStudy
DiseaseControlRatePa5ents–TimeonStudy• Forpa[entswhomet
DCR(N=44),themedian[meonstudywas20weeks
• Fourpa[entscon[nue
ontreatment>40weeks
10
PR=par[alresponse,SD≥12Weeks=stabledisease≥12weeks,PD=progressivedisease,WC=withdrewconsent0 5 10 15 20 30 55 80 105
OEOOCOOEOOCOOOEOOCCOEEOOOOOCOOOEEOOOOECOOOEO
Weeks Following Initiation of Selinexor Treatment
Canc
er T
ype
Progressive Disease
On Study
Withdrew Consent
PR PatientsSD ≥12 Weeks
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SIGN–ProgressionFreeSurvival(PFS),OverallSurvival(OS)
MedianProgressionFreeSurvivalandMedianOverallSurvival
• MedianPFSoverallfortheovarianpa[entswas3months,endometrial3months,andcervical1month
• MedianOSoverallfortheovarianpa[entswas7months,endometrial8months,andcervical5months
11
0 12 240
50
100
Months Elapsed
Perc
ent s
urvi
val
Progression Free Survival: Ovarian, Endometrial, Cervical
Ovarian (N=59)Endometrial (N=20)Cervical (N=23)
0 12 240
50
100
Months Elapsed
Perc
ent s
urviv
al
Overall Survival: Ovarian, Endometrial, Cervical
Ovarian (N=59)Endometrial (N=20)Cervical (N=23)
PresentedatESMOCongress2016byIgnaceVergote
Last update: 10-08-2016 01:46:24pm esmo.org
07-10-201610:15 - 11:45 Type: Educational session
Title: Cancer Immunotherapy (CIT): What every oncologist should knowVienna
Chair(s): S. van der Burg, NL; I. Melero, ES
10:15 - 10:30 Back to the basics
, Leiden, NLS. van der Burg
10:30 - 10:55 Cancer vaccines: Can we make them work?
, Leiden, NLC.(. Melief
10:55 - 11:20 T cell therapy: For whom and when?
, Herlev, DKI.-M. Svane
11:20 - 11:45 Immune checkpoints: Do we really know how they work?
, Pamplona, ESI. Melero
12:00 - 13:20 Type: Opening sessionTitle: Opening Session and Award lectures - Followed by welcome refreshments
Copenhagen
SIGN–Conclusions
• Singleagentselinexorhasinteres[ngan[-tumorac[vityinheavily-pretreatedovarianandendometrialcancerpa[ents,withdiseasecontrolformorethan12weeksof49%and45%intheOCandECcohort,respec[vely
• Themaintoxici[esofSelinexorarenausea,anorexia,fa[gue,andvomi[ng.Theseside
effectsaremanageablewithsuppor[vecare,especiallyinonceweeklydosing(50mg/m2)• Majororgantoxici[esarerarelyobserved• Clinicallysignificantcumula[vetoxici[esareuncommon
• Fiseenpa[ents(13%)remainedonsingleagentselinexor>6months,including4pa[ents
>12months• Combina[onstudiesareongoing&PhaseIIItrialsinOC&ECarebeingplanned
12