ANCO: ASCO Highlights 2018 …€¢Venis an oral BCL-2 inhibitor with activity in AML Pratzet al,...
-
Upload
vuongkhuong -
Category
Documents
-
view
214 -
download
0
Transcript of ANCO: ASCO Highlights 2018 …€¢Venis an oral BCL-2 inhibitor with activity in AML Pratzet al,...
9/4/18
1
ANCO:ASCOHighlights2018Hematologic Malignancies
BrianA.Jonas,M.D.,Ph.D.UC DavisComprehensiveCancerCenter
August25,2018
BrianJonas,MD,PhDANCO:ASCOHighlights2018
Relevantfinancialrelationshipsinthepasttwelvemonthsbypresenterorspouse/partner:
Consulting:AbbVie,Amgen,ToleroGrant/ResearchSupporttoInstitution:AbbVie,Pharmacyclics,Glycomimetics,DaiichiSankyo,Genentech/Roche,Celgene,Forma,Incyte,Esanex,AROG,AcceleratedMedicalDiagnostics,LP
Therapeutics.PatentsPending:AcceleratedMedicalDiagnostics
Thespeakerwilldirectlydisclosuretheuseofproductsforwhicharenotlabeled(e.g.,offlabeluse)oriftheproductisstillinvestigational.
9/4/18
2
ASCO2018 AnnualMeetingHeme Abstracts
• Abstract7000:Ivosidenib inmutantIDH1relapsed/refractoryacutemyeloidleukemia:ResultsofaPhase1study.
• Abstract7010:Durableresponsewithvenetoclax incombinationwithdecitabine orazacitidine inelderlypatientswithacutemyeloidleukemia.
• Abstract7502:Phase2CAPTIVATEresultsofibrutinib plusvenetoclax infirst-lineCLL.• Abstract8000:Once-weeklyvstwice-weeklycarfilzomibdosingplusdexamethasonein
patientswithrelapsedandrefractorymultiplemyeloma:Resultsoftherandomizedphase3studyA.R.R.O.W.
• Abstract8007:bb2121anti-BCMACART-celltherapyinpatientswithrelapsed/refractorymultiplemyeloma:UpdatedresultsfromamulticenterphaseIstudy.
Devel Theran=255 Leuk,MDS,Allo n=83 PlasmaCelln=60 LymphomaandCLLn=89
AbstractsCoveredn=5
Ivosidenib (IVO; AG-120) in mutant IDH1 relapsed/refractory acute myeloid leukemia (R/R AML): Results of a phase 1 study
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
Abstract7000
9/4/18
3
Isocitrate Dehydrogenase (IDH) Mutations as a Target in AML
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
IDH1R132
Study Design and Objectives
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
DatareportedonR/RAML500mg(n=179)fromescalationandArm1
9/4/18
4
AEs of Interest: R/R AML 500 mg (n=179)
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
OtherG3+TEAEin>1patient– febrileneutropenia(29.1%),anemia(20.1%),diarrhea(2.2%),fatigue(1.7%),dyspnea(3.9%),pyrexia1.1%)
Response in R/R AML 500 mg (n=179)
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
9/4/18
5
Overall Survival by Best Response in R/R AML 500 mg (n=179)
Presented By Daniel Pollyea at 2018 ASCO Annual Meeting
Overalltransfusionindependence:Platelet38.5%,RBC42.3%
Abstract7000 Conclusions
• Ivosidenib isanoralIDH1inhibitorthatiswelltoleratedandinducesdurableresponsesinpatientswithR/RIDH1-mutatedAML– Non-CR/CRh respondersalsohadfavorableOS– 23%ofCR/CRh respondersclearedIDH1mutation
• NeedtobeawareofIDH-DS• Studyimpact:
– ResultspublishedinNEJM2018;378(25):2386-98– Ivosidenib (Tibsovo)FDAapprovedon7/20/18– NewstandardofcareforR/RmIDH1AML
9/4/18
6
Durable Response with Venetoclax in Combination with Decitabine or Azacitidine in Elderly Patients with Acute Myeloid Leukemia
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
Abstract7010
Venetoclax andAML
• AML– medianageatdiagnosis68andptsareoftenineligiblefororrefractorytointensechemotherapy
• BCL-2ishighlyexpressedinAMLandisassociatedwithpooroutcomes
• Ven isanoralBCL-2inhibitorwithactivityinAMLPratz etal,BSH,#BSH18-OR-007.Mihalyova etal,Exp Hematol 2018.
9/4/18
7
Study Design and Objectives
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
*Venetoclax doserampedupfrom100mgto400mgor800mgover3-4days
Treatment Emergent Adverse Events (AE)
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
9/4/18
8
Response Rates by Treatment
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
CR/CRi andMRDNegative:29%overall45%Aza400
Duration of Response after CR/CRi
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
9/4/18
9
Overall Survival
Presented By Courtney Dinardo at 2018 ASCO Annual Meeting
Abstract7010 Conclusions
• ThecombinationofVen +HMAhassignificantactivityinelderlyandhighriskAML,includinghighCR/CRi rates,MRDnegativity,DoR andOS
• RegimenistolerablebutmanagementisverydifferentfromtypicalHMAmonotherapy
• Studyimpact:– ResultspublishedinLancetOncology2018;19:216-28– FDAbreakthroughdesignationforAML1/2016– Regimenisalreadybeingusedoff-labelbymanygroups– MaybecomethestandardofcareforelderlyAML- P3RDBPCtrialofAza+Ven vsAza+Placebo isongoing
9/4/18
10
Phase 2 CAPTIVATE Results of Ibrutinib Plus Venetoclax in <br />First-line Chronic Lymphocytic Leukemia (CLL)
Presented By William Wierda at 2018 ASCO Annual Meeting
Abstract7502
Introduction
Presented By William Wierda at 2018 ASCO Annual Meeting
9/4/18
11
Phase 2 CAPTIVATE Study Design (NCT02910583)
Presented By William Wierda at 2018 ASCO Annual Meeting
Most Common Adverse Events* by Time of Onset in <br />All Treated Population (N=164)
Presented By William Wierda at 2018 ASCO Annual Meeting
9/4/18
12
Deep Responses Achieved With 12 Cycles I+V With Undetectable MRD in PB and BM
Presented By William Wierda at 2018 ASCO Annual Meeting
UndetectableMRDis<1CLLcellper10,000leukocytes(<10-4)by8-colorflow
Early Undetectable MRD Responses Sustained Over Time
Presented By William Wierda at 2018 ASCO Annual Meeting
9/4/18
13
Abstract7502 Conclusions
• ThecombinationofibrutinibandvenetoclaxinduceshighratesofresponseandMRDnegativeresponseinuntreatedCLL,includingdel(17p).
• Tumordebulkingwithibrutiniblead-inphasedecreasedriskofTLSwithvenetoclax
• Studyimpact:– Bothibrutinibandvenetoclax (after1priorRx)areapprovedinCLL
– Promisingcombinationthatmeritsfurtherstudy– P3trialevaluatingI+Vfixeddurationin1stlineCLL
Once-weekly Versus Twice-weekly Carfilzomib Dosing in Patients with Relapsed and Refractory Multiple Myeloma: Results of the Randomized Phase 3 Study A.R.R.O.W.
Presented By Maria-Victoria Mateos at 2018 ASCO Annual Meeting
Abstract8000
9/4/18
14
A.R.R.O.W.StudyBackground
• CarfilzomibapprovedforRRMM– Singleagent:20/27mg/m2days1,2,8,9,15and16ona28dschedule
– Kd:20/56mg/m2days1,2,8,9,15and16ona28dschedulewithDex (ENDEAVOR)
– KRd:20/27mg/m2days1,2,8,9,15and16ona28dschedulewithLenandDex (ASPIRE)
• CHAMPION-1studyinRRMMestablishedMTDforweeklyCarfilzomibat70mg/m2
A.R.R.O.W. Study Design
Presented By Maria-Victoria Mateos at 2018 ASCO Annual Meeting
9/4/18
15
Hematologic and Nonhematologic Adverse Events <br />
Presented By Maria-Victoria Mateos at 2018 ASCO Annual Meeting
Safetyfindingsconsistentwithknownsafetyprofileofcarfilzomib,includingrisksofneuropathy,renalfailure,cardiacfailure,ischemicheartdiseaseandpulm HTN.
Overall Response Rates
Presented By Maria-Victoria Mateos at 2018 ASCO Annual Meeting
9/4/18
16
Primary Endpoint: PFS<br />
Presented By Maria-Victoria Mateos at 2018 ASCO Annual Meeting
NosignificantdifferenceinOS(medianNRforbotharms)
Abstract8000 Conclusions
• Once-weeklyKd at70mg/m2improvedPFSandORRcomparedtotwice-weeklyKd at27mg/m2
• Overallsafetyprofilewascomparable• Studyimpact:
– ResultspublishedinLancetOncology2018;19(7):953-64
– AnewconvenienttreatmentoptioninRRMMthatappearstobesafeandeffective
– Overall,however,theoptimalscheduleanddoseofcarfilzomibremainsunclear(e.g.1vs2timesweekly,27mg/m2vs56mg/m2vs70mg/m2)
9/4/18
17
ABSTRACT 8007
Presented By Noopur Raje at 2018 ASCO Annual Meeting
Abstract8007
Slide 2
Presented By Noopur Raje at 2018 ASCO Annual Meeting
BCMA(B-cellmaturationantigen)ishighlyexpressedinMMandisnotexpressedinnormalhumantissuesexceptforplasmacells.
9/4/18
18
Slide 4
Presented By Noopur Raje at 2018 ASCO Annual Meeting
Slide 7
Presented By Noopur Raje at 2018 ASCO Annual Meeting
CRS– 39%(noG3)at150x106 cellsand82%(noG4,9%G3)at>150x106 cellsMediantimetoonset2d(1-25)
9/4/18
19
Slide 10
Presented By Noopur Raje at 2018 ASCO Annual Meeting
MRD-evaluableresponders(n=16)– 100%wereMRD-neg(<1x10-4 byNGS)
Slide 12
Presented By Noopur Raje at 2018 ASCO Annual Meeting
9/4/18
20
Abstract8007 Conclusions
• bb2121atactivedoses(≥150x106 CART-cells)inducesdeepanddurableresponsesinheavilypretreatedRRMM
• TolerablesafetyprofilewithmostlyG1/2CRSandinfrequenttocilizumabandsteroiduse
• Studyimpact:– FDAbreakthroughdesignationforRRMM11/2017– Anti-CD19CART-cellsareapprovedforR/RaggressiveB-cellNHLandR/RB-ALL,andthisstudyshowsthataCART-cellplatformforMMisalsofeasibleandeffective
SummaryandTakeHomePoints
• Ivosidenib isanoralmIDH1inhibitorandisanewstandardofcareforR/RIDH1-mutatedAML.IDH-DSisapossibledangeroussideeffect.
• Venetoclax plusHMAhassignificantactivityinelderlyAMLandmayultimatelybecomethestandardofcareforolderunfitAML.ManagementisverydifferentfromstandardHMAmonotherapy.
• Thecombinationofibrutinibplusvenetoclax ishighlyactiveandinducesahighrateofMRDnegativeresponsesin1st lineCLL.TheregimenhaspotentialtobecomeastandardregimenforCLL.
• Convenientonceweeklycarfilzomib70mg/m2dosingplusdexappearssafeandeffectiveinRRMMandrepresentsanewtreatmentoption.Theoptimaldoseandscheduleofcarfilzomibremainsunclear.
• Anti-BCMACART-celltherapyhasatolerablesafetyprofileandiseffectiveinRRMM,andmayultimatelyjointhelistofapprovedCART-celltherapies.
9/4/18
21
OtherAbstractsofPotentialInterest
• Abstract7001:EarlyHMAforlowriskMDS
• Abstract7002:Bosutinib vsimatinib firstlineforCML
• Abstract7003:Long-termTFRaftersecond-linenilotinibdiscontinuation
• Abstract7004:moxetumomabpasudotox forR/Rhairycellleukemia
• Abstract8003:ibrutinib/rituximabvsplacebo/rituximabinR/RWM
• Abstracts8015,8017,8022and8032:carfilzomibscheduleanddosing
• Abstract8025:autotransplant inMMfeasibleinages75+
• Abstract7500:lenaidomide plusrituximabvschemoplusrituximabfollowedbyrituximabmaintenanceforuntreatedfollicularlymphoma
• Abstract7501:acalabrutinib foruntreatedandR/RWM
• Abstract7504:anti-CD47plusrituximabforR/RNHL
• Abstract7508:HighratesanddurabilityofMRD- withvenetoclaxplusrituximabinR/RCLL
• Abstract7515:RituximabmaintenanceafterBRinMZL