Partnering Partnering with Industrywith Industry

Katherine Y. Look M.D. Katherine Y. Look M.D.

Medical Fellow IMedical Fellow I

Eli Lilly Eli Lilly NCI/GCIG Panel DiscussionMay 29, 2009

Partnering Partnering Industry Industry PerspectivePerspectiveWhat we BringWhat we Bring

Novel MoleculesNovel MoleculesGlobal PresenceGlobal PresenceAdvocacy LinksAdvocacy LinksFinancial supportFinancial support

What we NeedWhat we Need

TimelinessTimeliness

ConceptConcept→PA→FPV→PA→FPV

RegulatoryRegulatory Quality Quality Data Data CollectionCollection

Cooperation with Cooperation with CTR CTR

RequirementsRequirements

Pfisterer J et al JCO 2006

Pfisterer J et al JCO 2006

Pfisterer J et al JNCI 2006

Pfisterer J et al JNCI 2006

TFI 12 mos

Ferrero JM et al Annals Oncology 2007

Ferrero JM et al Annals Oncology 2007

CALYPSOCALYPSO

Sponsors and CollaboratorsSponsors and Collaborators: :

ARCAGY/ GINECO GROUP ARCAGY/ GINECO GROUP

Schering-Plough Schering-Plough

Arbeitsgemeinschaft Arbeitsgemeinschaft Gynaekologische Onkologie Gynaekologische Onkologie Austria AGO Ovarian Cancer Austria AGO Ovarian Cancer Study Group Study Group

ANZGOG ANZGOG

European Organization for European Organization for Research and Treatment of Research and Treatment of Cancer Cancer

NCIC CTG NCIC CTG

NSGO NSGO

ClinicalTrials.gov Identifier: ClinicalTrials.gov Identifier: NCT00189553NCT00189553

StandardStandardCarboplatin AUC 5 every 3 Carboplatin AUC 5 every 3 or 4 weeks or 4 weeks Paclitaxel 175 mg/m² at Paclitaxel 175 mg/m² at day 1 every 3 weeks day 1 every 3 weeks

Experimental Experimental Carboplatin AUC 5 every 3 Carboplatin AUC 5 every 3 or 4 weekor 4 week Pegylated liposomal Pegylated liposomal doxorubicin 30 mg/m² doxorubicin 30 mg/m² every 4 weeks every 4 weeks

6 cycles or until 6 cycles or until progressionprogression

CALYPSOCALYPSO

Eligibility CriteriaEligibility Criteria

Measurable disease (RECIST) Measurable disease (RECIST) oror

CA125 assessable disease (GCIG) CA125 assessable disease (GCIG) oror

Histologically proven Dx of relapseHistologically proven Dx of relapse

Progression > 6 m after 1Progression > 6 m after 1stst or 2 or 2ndnd Platinum Platinum

based therapy. Prior taxane derivativebased therapy. Prior taxane derivative

required.required.

ECOG PS < 2ECOG PS < 2

Adequate organ function Adequate organ function

Exclusion CriteriaExclusion Criteria

LMP tumorsLMP tumors

Prior RTPrior RT

Prior other malignancyPrior other malignancy

Pre-existing NCI CTCAE neurotox > G1Pre-existing NCI CTCAE neurotox > G1

Severe hypersensitivity to Cb, Pac, CaelyxSevere hypersensitivity to Cb, Pac, Caelyx

11•• Outcome Measure Outcome Measure: :

PFSPFS

2 2 • • Outcomes Measure(s): Outcomes Measure(s):

Toxicity, Toxicity,

QOL, QOL,

OSOS

Enrollment: Enrollment: 976976

Start Date: Start Date:

April 2005April 2005

Estimated Completion Date: Estimated Completion Date:

November 2012November 2012

http://www.clinicaltrials.gov/ct2/show/NCT00189553 accessed May 4

, 2009 , 2009

Challenges Challenges OpportunitiesOpportunities

Intellectual Intellectual PropertyPropertyBiomarkerBiomarker-Pt -Pt SegmentationSegmentation

ContractingContracting

DataData

NDANDA

sNDAsNDA

Timeline(s)Timeline(s)

Stakeholder Stakeholder dialogue Safe dialogue Safe harborharbor

Common ClausesCommon Clauses

StreamlinedStreamlined

OptimizedOptimized

Standardized/caBIGStandardized/caBIGSurrogate Endpoints Surrogate Endpoints

(PFS -Ind/Review-EBM)(PFS -Ind/Review-EBM)

Curt G; McClellan M, Benner JS; Niederhuber JEThe Oncologist 2009 in press

DiscussionDiscussion

Common GoalsCommon Goals

OS, PFS, QOL GainsOS, PFS, QOL Gains

Rapid Accrual Rapid Accrual

Lessons Learned Lessons Learned

What is working….What is working….

What is slowing us What is slowing us down..down..

Examples (if desired) Examples (if desired)

-- Platin resistant Platin resistant

- Front Line - Front Line therapytherapy

Registration Endpoints: Registration Endpoints: Industry PerspectiveIndustry Perspective

Platinum Resistant Platinum Resistant Recurrent Ovary Recurrent Ovary CancerCancerAgent/Dose Author/YR RR% M PFS (m) M OS (m)

Alimta 500 Vergote 09 9.3 2.8 11.9

Alimta 900 Vergote 09 10.4 2.8 10.3

Alimta 900 Miller 09 21 2.9 11.4

L. Doxil 50 vs Topo

Gordon 04 12 2.3 8.9

L. Doxil 50 vs gemcitabine

Mutch 07 11.7 3.1 13.5

L. Doxil 50 vs Trabectedin + L Doxil

Monk 08* ESMO, IGCS abstract only

12.2 3.7 NA

Platinum Resistant Platinum Resistant Ovary Cancer: Proposals Ovary Cancer: Proposals UD UD GOGGOG

Phase 3: 2 X 2 Factorial design Phase 3: 2 X 2 Factorial design Docetaxel vs LD with concurrent Docetaxel vs LD with concurrent randomization w/wo VEGF Traprandomization w/wo VEGF Trap

SGCTGSGCTG‡‡: RP2 N = 250 1: RP2 N = 250 1○○EP PFSEP PFSddCb3T80 3/4wk X 18 vs LD 50 Q4ddCb3T80 3/4wk X 18 vs LD 50 Q4

EORTCEORTC‡‡

Picoplatin phase 2/3 (Poniard)Picoplatin phase 2/3 (Poniard)EORTCEORTC‡‡

HDAC Inhibitor phase 2HDAC Inhibitor phase 2

‡‡ discussed at GCIG November 2008 discussed at GCIG November 2008

GCIG Proposals UD Nov 08 GCIG Proposals UD Nov 08 Has FPV Occurred? Has FPV Occurred?

AGO 12AGO 12: : CbCb55TT175 175 vs Cbvs Cb55TT175175 BIBF 1120 200 bid BIBF 1120 200 bid

N = 1300N = 1300

11○○EP: PFS EP: PFS

22○○ EP: OS, PFI, CA125, QOL EP: OS, PFI, CA125, QOL

AGO 16AGO 16: : DC lst line +/- Pazopanib (GSK)DC lst line +/- Pazopanib (GSK)

11○○EP: PFSEP: PFS

Schedule: CA125 Q3m X 18 m: CT Q6Schedule: CA125 Q3m X 18 m: CT Q6

FPV = First Patient Visit