CCAFMARCH 3, 2008

Translational Oncology Research International (TORI)

Developed out of original UCLA Oncology Network

Not-for-profit 501(c)3 organization dedicated to early phase translational research

TORI Research Network (US)

8 states: California, Nevada, Florida, Georgia, Indiana, Texas, Maryland, and New Mexico (Hawaii , Colorado, Illinois and Alaska pending)

25 sites, 57 offices, 149 investigators2

US TORI Oncology Research NetworkUS TORI Oncology Research Network

Translational Oncology Research International (TORI)

501(c)3: Applies to corporations or foundations organized or operated exclusively for religious, charitable, scientific, literary, sports or educational purposes.

Mission Statement

Board of Directors

Articles of Incorporation (TORI = Delaware, 2003)

By-laws

Budget , Record Keeping, Accounting System

State and local tax exemption

Challenges for JCCC Division of Clinical Research:JCCC based at tertiary medical center.Market forces.Competitive practices.

Opportunities for JCCC Division of Clinical Research:Institutional sparse.Population dense.

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How to Increase Accrual?IS A COMMUNITY-BASED ONCOLOGY

RESEARCH NETWORK POSSIBLE?2002 - 2003

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Cancer Incidence by Ethnicity All Cancers

County White Black Hispanic Asian-Pacific IslanderAll RacesFresno 5,882 365 1319 335 8,143Kern 5,356 366 263 120 2,051Los Angeles 61,842 13,052 16,462 9,019 102,053Monterey 3,085 157 545 297 4,293Orange 25,062 318 2,642 2,070 30,981Riverside 15,673 824 1,802 332 19,328San Diego 26,735 1,276 3,047 1,720 33,490Ventura 6,969 135 959 294 8,585TOTALS 150,604 16493 27039 14187 208,924

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Cancer Incidence by Ethnicity All Cancers

County White Black Hispanic Asian-Pacific IslanderAll RacesLos Angeles 12,267 2,668 3,587 1,984 20,862Fresno 1,209 50 310 64 1,724Orange 5,139 49 595 448 6,466Riverside 3,240 182 416 76 4,043San Diego 5,281 243 665 360 6,780Ventura 1,473 10 205 54 1,803Kern 1,020 67 166 1,369TOTALS 28,609 3,202 5,778 2,986 41,678

UCLA-TORI Network HistoryPart One

1976: UCLA receives “Comprehensive” status

1992: HER-2 trials: Slow accrual at UCLA

1993: Local Oncologists approached about UCLA affiliation

1995: First UCLA Oncology Network patient enrolled

2002: Network enrolling 60 to 80 patients a month

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Institutional Barriers to UCLA Community Network Research

Contracts and GrantsOne UCLA contract, negotiated on University

terms with UCLA PI

IRBOne UCLA PI, Network investigators are sub-

investigators

Central Pharmacy Drug distribution to sites OK, indirect funds not

used to increase pharmacy staff

UCLA had to open before the Network could start = SLOW

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Accrual to Trials Open in Both UCLA and Network

0

50

100

150

200

250

300Network

UCLA

UCLA-TORI Network HistoryPart Two

2002: UCLA Regents/Lawyers stopped new Network studies/contracts – enrollment < 8/month

2003: UCLA-TORI Memorandum of Agreement

2003: TORI - Translational Oncology Research International incorporated in Delaware, August 2003

2003: First TORI patient enrolled October 2003

2004: First ex-US TORI patient enrolled in Ireland, Canada, currently India pending

To present: Over 4,000 enrolled on > 160 UCLA or TORI Network therapeutic trials

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Translational Oncology Research International (TORI)

US Sites

Primarily single or multiple physician community practices – several hospital based practices

Most can use central IRB, some have local IRB

Most now conduct private research plus TORI studies

Non-exclusivity contract with TORI – all practice physicians sign

TORI has accrual goals per site, not per study

TORI provides/trains research staff for TORI studies

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TORI Research Investigator network (US + ex-US)TORI Research Investigator network (US + ex-US)

TORI Principal Investigator at each siteTORI Principal Investigator at each site

UCLA scientists, researchers and laboratoriesUCLA scientists, researchers and laboratories

Phase I (UCLA/selected TORI sites), Phase II-III TORI Phase I (UCLA/selected TORI sites), Phase II-III TORI and UCLAand UCLA

Central IRB (Western IRB) or local IRB (if needed)Central IRB (Western IRB) or local IRB (if needed)

Central contracts , budgets and site paymentsCentral contracts , budgets and site payments

Central drug distribution – separate UCLA TORI Central drug distribution – separate UCLA TORI investigational pharmacyinvestigational pharmacy

Translational Oncology Translational Oncology Research International (TORI)Research International (TORI)

JCCC Internal Scientific Peer Review Committee JCCC Internal Scientific Peer Review Committee review of studiesreview of studies

JCCC Quality Assurance oversight/audit of studiesJCCC Quality Assurance oversight/audit of studies

JCCC/TORI central monitoring of Investigator JCCC/TORI central monitoring of Investigator Initiated studiesInitiated studies

Liaison coordinators/command center to review Liaison coordinators/command center to review eligibility requirements of ALL patientseligibility requirements of ALL patients

Translational Oncology Translational Oncology Research International (TORI)Research International (TORI)

Central site managementCentral site management

Central project managementCentral project management

Central regulatory submissions and file Central regulatory submissions and file maintenancemaintenance

Central or local sponsor monitoringCentral or local sponsor monitoring

eVelos system… coming sooneVelos system… coming soon

Indirect rate/TORI funds = returned to JCCC Indirect rate/TORI funds = returned to JCCC to support research infrastructureto support research infrastructure

Translational Oncology Translational Oncology Research International (TORI)Research International (TORI)

TORI StudiesOver 4,000 patients enrolled in more

than 160 studies conducted across multiple tumor sites Breast , lung, colon, anemia of cancer,

lymphoma, prostate, bladder, ovarian, melanoma, pancreatic, renal, bone mets.

Participated in registrational studies includingHerceptin, Avastin, Gleevec, Tarceva,

Aranesp, Iressa, Zoledronate, Erbitux

Multiple FDA, QA, sponsor audits (because of high enrollment)

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TORI International SitesOpen Sites:

Canada Edmonton: Cross Cancer Institute Montreal: McGill University

Ireland (Irish Clinical Oncology Research Group ICORG) Belfast: Belfast City Hospital, Belvoir Park Hospital Cork: Cork University Hospital, South Infirmary Victoria Hospital,

Mercy Hospital, Bon Secours Hospital Dublin: St. Vincent’s University Hospital, St. James Hospital, Mater

Misericordiae University Hospital, Mater Private Hospital, Beaumont Hospital

Galway: University College Hospital Limerick: Mid-Western Regional Hospital Sligo: Sligo General Hospital Waterford: Waterford General Hospital

Pending Sites: India:

Mumbai/Bombay: Tata Memorial Hospital, Jaslok Hospital and Research Centre

Hyderabad: Nizam’s Institute of Medical Sciences New Delhi: Rajiv Gandhi Cancer Institute & Research Center, All

India Institute of Medical Sciences, Jessa Ram Hospital Pune: Deenanath Mangeshkar Hospital & Research Centre17

JCCC Clinical Research UnitTORI Network Central Administration

SlamonDirector

GlaspyCo-Director

RybaAdministrative Director

McDonaldAssistant Director

TORI NETWORK

National Sites (25)International Sites (20)

Total Staff (55)

JCCC CRUREGULATORY &TORI CENTRAL

ADMIN

Total Staff (30)

TORI NetworkResearch Staff

-National Site Staff (54)-International Site Staff(37*)

* staff do not report toCRU

JCCC CRU Teams(Indirect Reporting)

-Team Leaders (2)-Coordinators (9)-Data Managers (6)-Clinic Coordinator (1)-Assistants (3)

TBNNetwork Field

Operations Manager

GrubbCRU-Network

Regulatory Manager

MuffTORI Chief Financial Officer

Business Director

BarkerCRU Financial Operations

Manager

CRU-TORI Admin &Financial Offices

-Fund Managers (4)

-TORI Financial Assistant(1)

CRU-TORI Assistants (3)

CRU-TORIADMINISTRATIVE &

FINANCIAL OPERATIONS

Total Staff (10)

JCCC OFFICE OFREGULATORYCOMPLIANCE

-Admin Director (1)-QA Monitor-ISPRC (1)-TORI Network Monitors (4)-Assistants (2)

UCLA PHARMACYDEPARTMENT

-UCLA InvestigationalPharmacist (3)-TORI InvestigationalPharmacist (1)

TORI-CIRG

Monitors TORIInvestigator-Initiated Studies

UCLA JCCC CLINICALRESEARCH UNIT

Total Staff (46)

JCCC CRU Teams(Direct Reporting)

-Team Leaders (4)-Coordinators (12)-Data Managers (8)

SpaargarenCRU Operations

Manager

JCCC CRU RegulatoryTORI Central

Administration Teams

-TORI Central AdminSupervisors (2)-TORI Clinical ResearchSpecialists (9)-Liaison Coordinators (2)-Database Coordinator (1)-CRU Direct Regulatory (8)-CRU Indirect Regulatory(7)

UCLA CRU-TORI Organizational

Chart

-UCLA TORI

Memorandum of UnderstandingMOU

-UCLA TORI

Director, Clinical Research Dennis Slamon

-Director, CRU TORI Nancy Ryba

TORI Board of Directors

Dennis Slamon John Mackey John Glaspy Fran Visco Carol Cass

TORI Officers

Chief Medical Officer Fairooz Kabbinavar

Chief Financial Officer Jim Muff

- CRU TORI Administration

Assistant Director Audrey McDonald

- - Operations Regulatory Financial Managers Andrea Barker

Chela Spaargaren Nikko Grubb

TBA

- TORI UCLA Network Sites and Staff

UCLA CRU Research Teams

TORI Central Administration Teams

TORI Liaison Coordinators Renee Robinson

Glaucia Vasquez

- TORI CRU Central Monitoring Senior Manager

- Lii Shin Lin

Central Monitoring Team (3)

TORI Admin Supervisors Gustavo Zetino

TBA

Clinical Research Specialists9( )

TORI Financial Assistant Kathy Farenbaugh

TORI Organizational Chart

Trastuzumab (Herceptin) - breast **Trastuzumab (Herceptin) - breast ** Rituxamab (Rituxan) - lymphoma Rituxamab (Rituxan) - lymphoma Imatinib (Gleevec-STI-571) - cml, gist **Imatinib (Gleevec-STI-571) - cml, gist ** Erlotinib (Tarceva-OSI-774) - lung **Erlotinib (Tarceva-OSI-774) - lung ** Gefitinib (Iressa-ZD1839) - lung **Gefitinib (Iressa-ZD1839) - lung ** Cetuximab (Erbitux-C225) - colonCetuximab (Erbitux-C225) - colon Bevacizumab (Avastin) - colon, lung **Bevacizumab (Avastin) - colon, lung ** Sorafenib (Nexavar-BAY43-9006) - hepatocellular, renalSorafenib (Nexavar-BAY43-9006) - hepatocellular, renal Sunitinib (Sutent-SU11248) - renal **Sunitinib (Sutent-SU11248) - renal ** Dasatinib (Sprycel-BMS-354825) - cml, breast **Dasatinib (Sprycel-BMS-354825) - cml, breast ** Panitumumab (Vectibix-ABX-EGF) - colorectal **Panitumumab (Vectibix-ABX-EGF) - colorectal ** Lapatinib (Tykerb-GW572016) - breast **Lapatinib (Tykerb-GW572016) - breast ** Bortezomib (Velcade-PS-341) – multiple myeloma, mantle cell lymphomaBortezomib (Velcade-PS-341) – multiple myeloma, mantle cell lymphoma Temsirolimus (Torisel-CCI-779) – renalTemsirolimus (Torisel-CCI-779) – renal Pemetrexed (Alimta-LY231514) – lungPemetrexed (Alimta-LY231514) – lung Telcyta (TLK-286) – lungTelcyta (TLK-286) – lung Zoledronate (Zometa) – bone metastasis **Zoledronate (Zometa) – bone metastasis ** Aranesp (NESP) – anemia of cancer **Aranesp (NESP) – anemia of cancer ** Palifermin (Kepivance-KGF) – cancer treatment-induced mucositisPalifermin (Kepivance-KGF) – cancer treatment-induced mucositis

** = number 1,2 or 3 accrual nationally or internationally** = number 1,2 or 3 accrual nationally or internationally

UCLA-TORI Accrual SuccessesUCLA-TORI Accrual Successes

• 1995: First UCLA Oncology Network patient enrolled1995: First UCLA Oncology Network patient enrolled

• 1997: BCIRG founded in collaboration with Alberta Cancer 1997: BCIRG founded in collaboration with Alberta Cancer Board in EdmontonBoard in Edmonton

• 1999: CIRG incorporated – BCIRG first Oncology division1999: CIRG incorporated – BCIRG first Oncology division

• 1999: BCIRG – UCLA collaborate on 11999: BCIRG – UCLA collaborate on 1stst HER2 studies HER2 studies

• 2000: CIRG Paris office opened2000: CIRG Paris office opened

• 2003: TORI - Translational Oncology Research 2003: TORI - Translational Oncology Research International formed in August 2003 – 1International formed in August 2003 – 1stst patient enrolled patient enrolled October 2003October 2003

• 2004: First ex-US patient enrolled on TORI studies2004: First ex-US patient enrolled on TORI studies

• 2004: TORI-CIRG enter into strategic alliance 2004: TORI-CIRG enter into strategic alliance

• 2006: TRIO (Translational Research in Oncology) developed2006: TRIO (Translational Research in Oncology) developed

The Past (Part Three) and the FutureThe Past (Part Three) and the FutureTRIO (TORI-CIRG) HistoryTRIO (TORI-CIRG) History

Cancer International Research GroupCIRG

Not-for-profit Canadian organizationAcademic LeadershipGlobal Investigator NetworkContract Research Organization Experienced Staff Flexible and DedicatedHigh quality data

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Worldwide Network of 2,000 Investigators Worldwide Network of 2,000 Investigators comprised of 500 centers in 45 countries comprised of 500 centers in 45 countries spanning 5 continents. spanning 5 continents.

Independent InvestigatorsIndependent Investigators

Cooperative groups: ANZ-BCTG, Cooperative groups: ANZ-BCTG, GERCOR, GEICAM, GBG, ICORG, US GERCOR, GEICAM, GBG, ICORG, US Oncology, TORI Oncology Research Oncology, TORI Oncology Research NetworkNetwork

CIRG Investigator NetworkCIRG Investigator Network

CIRG Enrolling RegionsCIRG Enrolling Regions

CIRG Study Successes BCIRG 001: Adjuvant Ph 3, Node +, 1491 patients – 118 sites

in 20 countries – TAC regimen approved by FDA August 2004

BCIRG 005: Adjuvant Ph 3, Node +/HER2- 3301 patients in 320 sites in 38 countries

BCIRG 006: Adjuvant Ph 3, Node +, HER2+ 3200 patients in 393 sites in 40 countries

BCIRG 101: Metastatic Ph2, 1st line HER2+ pilot study for TCH combination – 62 patients in 10 sites

BCIRG 007: Metastatic Ph3, 1st line HER2+ 263 patients – 80 sites

BCIRG 103: Neoadjuvant presurgical treatment, tissue collection – 59 patients in 21 sites in 7 countries

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Scientific Development (UCLA)Scientific Development (UCLA)

Medical Supervision (UCLA)Medical Supervision (UCLA)

BiostatisticsBiostatistics

Information TechnologyInformation Technology

Data ManagementData Management

Project ManagementProject Management

Monitoring ResourcesMonitoring Resources

Drug Safety and PharmacovigilanceDrug Safety and Pharmacovigilance

Quality AssuranceQuality Assurance

Finance and Administration (CIRG-TORI)Finance and Administration (CIRG-TORI)

TRIO Clinical OperationsTRIO Clinical Operations

TRIO – UCLA InfrastructureTRIO – UCLA Infrastructure

Data Management CIRG - Edmonton Office

• Data Management • Information Technology• Finance• Scientific Development• Logistics

CIRG - Paris Office

• Project Management• Monitoring Resources• Drug Safety and Pharmacovigilance• Quality Assurance• Finance

UCLA-TORI Office•University Laboratories and Clinics•Scientific Development - Medical Mgmt•Site Management•Regulatory Affairs – Project Management •Finance

The Path ForwardClinical Research

Translate preclinical findings into clinical research

Conduct innovative clinical research across all phases of drug development and multiple indications.

Develop and implement clinical operation models for registration and non registration trials

Consolidate the existing infrastructure28