CTNeT Overview ASCO 2012

Partner in Clinical Development

ASCO 2012

Cancer Product Development

2

The Problem Opportunity CTNeT Response

• Diagnosis and treatment by anatomical location and histology with limited molecular characterization

• Difficulty defining subsets likely to benefit

• Broad applications of treatments

• Lengthy, costly drug development with incremental gains

• Large number of negative Phase 3 studies

• Biorepository and registry to identify patients for trials based on prospective molecular characterization

• Streamline processes for efficient study start-up, execution, and completion

leading to

• Greater outcome gains in patient subsets

• Fewer negative Phase 3 studies

• More effective personalized medicine tailored to the needs of the patient

• Molecular biomarker testing coming into mainstream – personalized medicine (PM)

• FDA addressing challenges of new agent development in era of PM

• Consensus that old clinical trial model must be transformed

• CTNeT has funding to create a new clinical trial operating model – no legacy programs

Mission Statement

To transform cancer research and care bycombining the innovative science of ourcancer centers with the expertise and resources of academic and community

oncologists throughout Texas

3

Genesis of CTNeT

4

• 2007: Texas voters approved a 10-year, $3 billion bond fund to create the Cancer Prevention and Research Institute of Texas (CPRIT)

• 2010: CPRIT funded a grant to establish CTNeT as a 501(c)(3) organization to conduct statewide clinical cancer trials. CTNeT’s main tenets are to:

• Conduct statewide, tissue-based, and biomarker-driven clinical trials focused on making substantive advances in personalized care for cancer

• Collaborate closely with the CPRIT-funded Texas Cancer Research Biorepository (TCRB)

• Implement a highly effective, cancer clinical trials model to improve the design, activation and conduct of clinical trials

Clinical Site Network

5

SCOTT & WHITE HEALTHCARE

TEXAS TECH HEALTH SCIENCES CENTER / COVENANT HEALTH SYSTEM

SOUTH TEXAS ONCOLOGY HEMATOLOGY AT START CENTER

ONCOLOGY CONSULTANTS, PACENTER for CANCER and BLOOD DISORDERS

TEXAS CHILDREN’S CANCER CENTER TEXAS ONCOLOGY

MARY CROWLEY CANCER RESEARCH CENTER

THE METHODIST HOSPITAL SYSTEM

UT SOUTHWESTERN MEDICAL CENTERUT MEDICAL BRANCH at GALVESTON

BAYLOR COLLEGE of MEDICINE

UT HEALTH SCIENCE CENTER at SAN ANTONIO

UT HEALTH SCIENCE CENTER HOUSTON / MEMORIAL HERMANN CANCER CENTER

UT MD ANDERSON CANCER CENTER

• Collection of research-quality biospecimens on standing tissue procurement protocols with costs covered by CTNeT

• Broad molecular characterization on all specimens to prospectively identify subsets of patients for clinical trials

• Characterization in central CLIA-certified lab - Cancer Genetics Laboratory (CGL) at Baylor College of Medicine (BCM)

• Collaboration with the Texas Cancer Research Biobank in the Human Genome Sequencing Center at BCM (1 of 3 NCI-designated whole genome sequencing centers)

• Biospecimen registry with annotated clinical information for investigator notification of future studies

Biorepository and Registry

6

Cancer Genetics Lab Tests

7

Over 140 cancer genetic tests:• FISH: Individual probes and disease-specific panels

• Mutation Analysis

• Gene amplification, deletions, insertions, base-pair mutations

• e.g. AKT, BRAF, BCR/ABL, C-KIT, EGFR, KRAS, P53…

• Next-Generation Sequencing (Ion Torrent)

• Cancer mutation panel (“actionable mutations”)

• 46 cancer-related genes, up to 739 mutations

• Sensitivity up to 5% for certain mutations

• Chromosomal Microarray Analysis (CMA)

• Whole genomic analysis: 1800 cancer-related genes

• 400-probe microarray (Agilent), looking for SNPs, heterozygosity

Biorepository and Registry

8

Patient Consent

Patient Registration Study Site

CTNeT Biorepository

Operations

Tissue submitted

Resultsreported

All test results stored in data warehouse

Tissue stored for future research

Communication with site for future potential studies

• Master clinical trial agreement with each site; study-specific work orders

• Reliance agreements for AAHRPP-accredited central IRB (Chesapeake)

• Reliance agreements for single scientific review

• Centrally negotiated single study budget

• Single Data Safety Monitoring Board

• Risk-based data monitoring

• Metrics to assess, refine and support decisions

• Stipend supported site-based research champions (PI / SPOC)

Operating ModelSimple – Streamlined – Scalable

9

Informatics Platform

10

• Medidata® : 21 CFR Part 11-Compliant EDC platform

• CTMS™: Study planning and management

• Milestones, recruitment tracking, subject visits, tracking queries, exemptions, deviations, SAEs, alerts

• Financial management

• Site monitoring

• Regulatory compliance

• Integration with Rave®, any EDC, IVRS, CTMS, financial or data-mart/OLAP system, MS Project/Excel

• AS2, SFTP and CDISC ODM-compliant data sharing

• BALANCE™: Randomization and trial supply management

Informatics Platform Cont.

11

• Medidata Rave®:

• Single platform supporting EDC and CDMS through industry standards-based architecture (CDISC)

• Flexibility to interface with legacy systems with limited integration options, e.g., via ASCII file import and export

• Plug-in architecture that facilitates the addition of new interfaces and functionality

• Open, documented application programming interface (API)

• ARISg™: Drug safety and pharmacovigilance

• SAS®: Statistical analysis

Clinical Operations

Tissue Testing, Biorepository

Site Operations

Drug Safety

Quality Assurance

Regulatory Affairs

Data Management, Biostatistics

12

Clinical Development

Business Development Budgets,

ContractsMedical Writing

Services

Governance

Scientific Steering Committee

Chair: D. Johnson, MD 

Central InstitutionalReview Board

Chair: TBD

Data SafetyMonitoring Board

Chair: TBD 

Independent Committees CTNeT Committees

Tumor Biology CommitteeChair: R. DuBois, MD, PhD

13

President and CMOC. Geyer, Jr. MD

Council of Principal Investigators

SVP, Clinical Development L. Paradiso, DVM, MBA

Vice President and COOP. Winger

Head of BiostatisticsA. Razmpour, Ph.D.

CTNeT 501 (c)(3)Board of Directors

Chair: W. Butler, MD

Executive LeadershipCharles E. Geyer, Jr., MD President and Chief Medical OfficerFormer Director of Medical Affairs - National Surgical Adjuvant Breastand Bowel Project

Linda J. Paradiso, DVM, MBASr. Vice President of Clinical DevelopmentFormer Head, Global Oncology Regulatory Affairs- AmgenFormer Head, Oncology Clinical Development - Pfizer La JollaFormer Head, Clinical Research- Agouron PharmaFormer Senior VP, Clinical and Regulatory Affairs- Salmedix

Neera Bhansali, PhD* Head of BioinformaticsFaculty Director, MS Health Informatics and Management Systems- Florida International University, MiamiFormer Director, Data Quality & Standards, - H. Lee Moffitt Cancer Center

Holly Powers, JDLegal Counsel - Jameson and Powers, PC

Patricia A. Winger Vice President and Chief Operations OfficerFormer VP of Research Operations - US Oncology Former VP, Business Integration- Sarah Cannon Research Institute

Dean J. Ferrigno, CPA, MBAVice President, FinanceFormer VP, CFO- Sarah Cannon Research InstituteFormer Head of Development Finance- Daiichi Sankyo

Paul Papagni, JD, CIP Vice President of Research Admin, ComplianceFormer Executive Director for Clinical Research- MD Anderson Cancer Center

Ahmad Razmpour, PhDVice President, BiostatisticsFormer Head, Immunology Statistics- Abbott Global Statistics and Data ManagementFormer Sr. Director II, Biostatistics- Wyeth Global Biostatistics & ProgrammingFormer Head, Biostatistics & Data Management- Cytogen Corporation

14

*Consultant

Board of DirectorsWilliam T. Butler, MD, ChairmanChancellor Emeritus- Baylor College of Medicine

Bruce A. Chabner, MDProfessor of Medicine, Harvard Medical SchoolDirector of Clinical Research, MGH Cancer Center- Massachusetts General Hospital

John D. CullenChief Executive Officer- DMX, Inc.

Carolyn DicksonExecutive Director- The O’Donnell Foundation

James H. Doroshow, MD (Govt. Liaison, non-voting)Director, Division of Cancer Treatment and DiagnosisSenior Investigator, Laboratory of Molecular Pharmacology- National Cancer Institute

Richard B. Gaynor, MDVP, Clinical Development and Medical Affairs, Oncology- Eli Lilly and Company

Alfred G. Gilman, MD, PhD (Ex-officio, voting)Chief Scientific Officer- CPRIT

William H. Gimson, III, MBA (Ex-officio, voting)Executive Director - CPRIT Sandra J. Horning, MDSenior VP, Global Head, Clinical DevelopmentHematology/Oncology- Genentech/Roche Patrick J. Loehrer, Sr., MDDirector, Indiana University Simon Cancer CenterAssociate Dean of Cancer ResearchH. H. Gregg Professor of Oncology, - Indiana University School of Medicine Richard L. Schilsky, MDProfessor of Medicine, Chief, Section of Hematology-OncologyDeputy Director, Comprehensive Cancer Center- University of Chicago, Biological Sciences Division Robert C. Young, MDPresident- RCY Medicine

15

Scientific Steering Committee

Richard A. Gibbs, PhDBaylor College of Medicine

Alfred G. Gilman, MD, PhDCPRIT

William H. Gimson, III, MBACPRIT

Beth A. Hellerstedt, MDTexas Oncology Susan G. Hilsenbeck, PhDBaylor College of Medicine David G. Poplack, MDTexas Children’s Cancer Center Elda RaileyResearch Advocacy Network

David H. Johnson, MD, FACPCommittee ChairUT Southwestern Medical Center

Arthur L. Beaudet, MDBaylor College of Medicine Donald A. Berry, PhDUT MD Anderson Cancer Center Hak Choy, MDUT Southwestern Medical Center Raymond N. DuBois, MD, PhDUT MD Anderson Cancer Center

Charles E. Geyer, Jr., MD, FACPCTNeT

Dipti RanganathanUT Southwestern Medical Center

Christopher O. Ruud, MDScott and White Healthcare

Joseph O. Schmelz, PhD, RN, CIP, FAANUT Health Science Center San Antonio Ian M. Thompson, Jr., MDUT Health Science Center San Antonio Daniel D. Von Hoff, MD, FACPTranslational Genomics Research Institute, (TGEN) Patricia A. WingerCTNeT

16

17www.ctnet.org