Welcome & Introduction

Sibylle HohlerGlobal Studies Leader

Professor Xavier PivotCHU Besancon, France

Welcome to the BEATRICE Investigator Meeting in Buenos Aires

Welcome to the study and site team members

Argentina Brazil Costa Rica

Mexico Peru

Independent Data

Monitoring Committee

Independent Data

Monitoring Committee

StatisticsCRO(IDDI)

StatisticsCRO(IDDI)

CTRU(University of Leeds)

Safety data

Efficacydata

Participating centres

Participating centres

CRO(Quintiles)

Clinical database

Safety data

Efficacydata

Medical SupportMedical Support

Independent Statistician

Independent Statistician

ROCHEROCHE

Event ReviewCommittee

Event ReviewCommittee

BEATRICE: Partnership between Academia and Roche

Trial Steering Group

Operational Partners

QuintilesResponsible for EC/IRB submissions and health authority submissions in selected countriesResponsible for site management (partial site selection, patient recruitment, site contracts, site monitoring)Responsible for all data management activities (database set up until database closure). Database held independently of Roche

Roche Country Study ManagersKeep relations to the sites to provide support on a local levelResponsible for co-monitoring

Roche Central TeamOverall cross-functional management i.e. Quintiles, CSMs, academic groupsMonitoring of study progress Ultimate decision making authority for operational aspects

BEATRICE Roche team members (Operations)

Mieke BorgsOperations Project

Leader

Christian AngstGlobal Studies Leader

Sibylle HohlerGlobal Studies Leader

Michaela WolfGlobal Study

Operations Manager

Shannon WhiteGlobal Study Operations

Manager

Birgit MazereelGlobal Studies Associate

BEATRICE Roche team members (Clinical Oncology, Statistics & Data Management)

Annabelle MonnetBio-Statistician

Louis ViviersClinical Scientist

Claire SenayClinical Science

Specialist

Patricia Gil-BazanClinical Science

Specialist

Anne RichouProject Data

Manager

Henry BennettStudy DataManager

Peter ChevertonClinical Science

Leader

Stefan SchererBiomarker Program Leader

Raj RallanGlobal Biosamples

Specialist

BEATRICE Roche team members (Biomarker)

BEATRICE Quintiles central team members

Jason JeffordProgramme Director

Farida Souami Project Manager Europe, Latin &

South America, South Africa

MurielCostantzer

EDC Manager

Sophie LambertData Management

Team Lead

Egle KamantauskaiteGlobal Clinical Team Lead

Welcome from the BEATRICE Trial Steering Group

Professor Xavier PivotCHU Besancon, France

BEATRICE Trial Steering Group (1)

David Cameron UK (Chair)

Richard BellAustralia

Rebecca DentCanada

John MackeyCanada

Christian JackischGermany

Xavier PivotFrance

BEATRICE Trial Steering Group (2)

Günther StegerAustria

Thomas Suter Switzerland

Louis ViviersRoche

Masakazu ToiJapan

Sibylle HohlerRoche

BEATRICE Translational Research Committee Chairs

Max ParmarUK

Annabelle MonnetRoche

Julia BrownUK

BEATRICE Trial Project Statisticians

Peter CarmelietBelgium

Stefan SchererRoche

Trial Steering Group (TSG) PartnershipTrial Steering Group

Richard Bell Australia David Cameron UKRebecca Dent Canada Christian Jackisch GermanyJohn Mackey CanadaXavier Pivot FranceGünther Steger AustriaThomas Suter SwitzerlandMasakazu Toi Japan

Julia Brown Independent Statistician/Head of Leeds CTRU

Max Parmar Independent Statistician, MRC

Sibylle Hohler Roche OperationsAnnabelle Monnet Roche StatisticsLouis Viviers Roche Clinical Science

Translational Research CommitteePeter Carmeliet BelgiumAndy Tutt UK

Stefan Scherer Roche BiomarkerProgram Leader

Louis Viviers Roche Clinical Science

Objectives

What is BEATRICE ?

Why treat breast cancer with an anti-angiogenic?

Why select ‘Triple Negative’ Breast Cancers?

What is the basic trial design?

How do we run a trial in an Academic-Pharma partnership?

ER/PR/HER2 -ER/PR/HER2 -

“basal-like”

The “Triple Negative” Breast Cancer

Estrogen Receptor (ER) negativeProgesterone receptor (PR) negative

Her2neu (HER2) negative

Arm A

Surgery

Randomisation with StratificationNodal status

ChemotherapyHormone receptors

Type of surgery

Central confirmation of HR & HER2 status

Chemotherapy

Arm B

Chemotherapy Bevacizumab

Early breast cancer“Triple negative” and/or Basal-like subtype

Efficacy and Safety Follow-up (year 2-7)

Trial End Points

Surveillance Bevacizumab

(Year 1)

BEATRICE

The clinical need“Triple negative” tumours associated with poor outcome

The opportunityAngiogenesis as a target

The targeted agentBevacizumab

The Partnership

AcademiaConceptPatients

RocheDrugInfrastructure

Leeds CTRUGovernance

BEATRICE Partnership → Protects the interests of women

Role of AcademiaAnalyses free from commercial concernsInterest in long-term outcome dataReflect clinical practice, not just regulatory view

Role of PharmaSafety reporting and monitoringHigh quality data management systemsFully-funded studyEstablished bio-repository

SAEs Narratives

Independent Data

Monitoring Committee

Independent Data

Monitoring Committee

StatisticsCRO(IDDI)

StatisticsCRO(IDDI)

CTRU(University of Leeds)

Safety data

Efficacydata

Participating centres

Participating centres

CRO(Quintiles)

Clinical database

Safety data

Efficacydata

Medical SupportMedical Support

Independent Statistician

Independent Statistician

ROCHEROCHE

Event ReviewCommittee

Event ReviewCommittee

Independent Data Monitoring Committee and its interaction with other involved parties

Trial Steering Group

Translational analyses

Samples only taken with explicit consent

Tumour samples taken at time of central eligibility review

All analyses conducted with agreement of Translational Research sub-committee

Can be done in Roche, academic lab or other labAll links to clinical data overseen by Independent statistician

All publications have to be approved by Trial Steering Group

Data ownership

All clinical and biological data

Owned by Roche

Access granted by IDMC

Controlled by Translational Subcommittee of TSG for publication and presentation

Controlled by Roche for Registration

Participating Countries at this Meeting: Site distribution

20 Sites, 130 patients• Argentina• Brazil• Mexico• Costa Rica• Peru

Countries involved

CanadaUSA Australia

ChinaHong Kong

JapanKorea

MalaysiaNew ZealandPhilippinesSingapore

TaiwanThailand

S Africa

ArgentinaBrazil

MexicoCosta Rica

Peru

AustriaBelgiumBosnia

Czech RepFinlandFrance

GermanyGreeceIsraelItaly

Macedonia

NetherlandsPoland

PortugalRomaniaRussiaSerbiaSpain

SwedenSwitzerland

UK

Timelines

N = 2530

First Patient Enrolled: Dec 2007

Last Patient Enrolled: Dec 2009

Efficacy analysis: After 388 primary endpoint events have been observed

End of study after 340 deaths have occurred

Agenda Day 1 AM – Thursday 24 April

10h15 Avastin® Development Plan Christian Angst

10h35 Anti-angiogenesis in Breast Cancer Peter Cheverton

10h55 Triple-negative Breast Cancer Dr Rebecca Dent

11h20 Coffee Break

11h50 Clinical Review of the BEATRICE Protocol: Part 1 Louis Viviers

12h40 Biomarker and Translational Medicine in BEATRICE Stefan Scherer

13h05 Q & A Panel & Audience

13h20 Lunch

Agenda Day 1 PM - Thursday 24 April

14h20 Clinical Review of the BEATRICE Protocol: Part 2 Louis Viviers

16h00 Q& A Session Panel & Audience

16h30 Coffee Break

17h00 ICH GCP Quiz Farida Souami

17h25Data Management for the BEATRICEStudy

Henry Bennett &Sophie Lambert

17h55 Wrap up Day 1

Agenda Day 2 – Friday 25 April 08h30 Review of Day 1 Sibylle Hohler

08h45Operations

Central testingManagement of study drug

Michaela Wolf

09h10 SDE Process Farida Souami

09h55 IVRS: A practical review Jason Jefford10h15 Coffee

10h45 eCRF completion: A practical review Henry Bennett & Sophie Lambert

12h00 SAE Reporting Egle Kamantauskaite12h25 Patient recruitment & Patient retention Jason Jefford12h40 Review of Day 1 & 2 (group quiz) Sibylle Hohler13h00 Meeting finish

09h25 BSR & RSR: A practical review Raj Rallan