Informatics in Breast Cancer Research I-SPY 2 TRIAL & TRANSCEND

1. Informatics in Breast Cancer Research I-SPY 2 TRIAL& TRANSCEND

2. Design goals of I-SPY 2 • Screen phase 2 agents in combination with standard chemotherapy in neoadjuvant setting • Endpoint is pCR • Intermediate endpoint is MRI Volume • Accelerate process of identifying drugs that are effective for specific breast cancer subtypes • Integration of biomarkers • Reduce the cost, time, and number of patients needed to get effective drugs to market • “threshold” is 85% predicted likelihood of success in a 300-patient phase 3 trial for drug-biomarker pair

3. Paclitaxel* + Investigational Agent E Paclitaxel* + Investigational Agent B Paclitaxel* + Investigational Agent A Paclitaxel* + Investigational Agent D Paclitaxel* + Investigational Agent C Paclitaxel* RANDOMIZE Screening ON STUDY MRI Biopsy Blood Draw MUGA/ECHO CT/PET Consent #2 Treatment Consent Tissue I-SPY 2 Adaptive Trial Design SURGER Y AC AC AC AC AC AC Consent #1 MRI Blood Draw MRI Blood Draw MRI Biopsy Blood Draw * HER2 positive participants will also receive Trastuzumab. An investigational agent may be used instead of Trastuzumab.

4. Paclitaxel* + Investigational Agent E Paclitaxel* + Investigational Agent D Paclitaxel* + Investigational Agent FG Paclitaxel* + Investigational Agent B Paclitaxel* + Investigational Agent C Paclitaxel* Paclitaxel* + Investigational Agent A RANDOMIZE Screening ON STUDY MRI Biopsy Blood Draw MUGA/ECHO CT/PET Consent #2 Treatment Consent Tissue I-SPY 2 Adaptive Trial Design SURGER Y AC AC AC AC AC AC AC Consent #1 MRI Blood Draw MRI Blood Draw MRI Biopsy Blood Draw * HER2 positive participants will also receive Trastuzumab. An investigational agent may be used instead of Trastuzumab.

5. Informatics Needs for Adaptive Clinical Trials – I-SPY 2 • Manage information across multiple sites • Data gathering must be closely monitored as the trial depends on rapid eligibility determination and therapeutic intervention - do not want to delay therapy • Randomization as a web service (automated - but with review) • Combining evaluation of drugs and biomarkers together • Biomarker data is of various types (arrays, imaging volume, numeric scales, etc..) • Scientists need access to data early and in an integrated fashion (one stop shopping)

6. What is TRANSCEND? TRANslational Informatics System to Coordinate EmergingBiomarkers, NovelAgents, and Clinical Data An IT Bundle to Support Adaptive Trials with Novel Agents and Emerging Biomarkers

7. TRANSCEND Objectives • Develop an information management infrastructure to support adaptive clinical trials like I-SPY 2 • Provide real-time data verification for more efficient analysis of trial data • Provide a demonstration of caBIGinfrastructure in use in a large multi-center trial • Demonstrate integration of a clinical system (electronic health record system) with a clinical research infrastructure

8. TRANSCEND - Systems Overview TolveneCHR Study Sites Case Report Forms caAers Data Coordinating Center Agendia  caArray MD Anderson Randomization Engine Integration Hub (caXchange) Research Labs caTissue Suite caIntegrator Automated interface Manual interface

9. TRANSCEND – eCHR Data Collection

10. Electronic copy of source documentation with each CRF Easy to complete case report forms with smart logic TRANSCEND – eCHR Data Collection

11. TRANSCEND – eCHR Data Verification • Instant submission of CRF with source documentation to Data Coordination Center • Real-time data review and verification

12. Email alerts to when a CRF is ready for review & verification Email alerts when a CRF is rejected by the DCC TRANSCEND – eCHR Data Collection

13. TRANSCEND - Randomization

14. Future Direction with 2TRANSCEND Integrate additional platforms • Web-based Patient Communication and Care Plan • Aids in decision making about participating in a clinical trial as well as enabling study staff to communicate with patient’s regarding study appointments • Web interface allowing patients to directly input: • Adherence to treatment regimens • Adverse events (PRO-CTCAE) • Follow-up information • Adopt Annotation Imaging Mark-up (AIM) tool to enable researches ability to centrally review and analyze images

15. 2TRANSCEND - Integrated Systems

16. TRANSCEND TEAM • Dr. Laura Esserman – I-SPY TRIAL, TRANSCEND PI (UCSF) • Dr. Michael Hogarth - TRANSCEND Technical Director (UC Davis) • Meg Young – TRANSCEND Project Manager (UCSF) • Sarah Davis – I-SPY 2 TRIAL Manager (UCSF) • Joyce Lee, Julia Lyandres (software testing, quality control) • Sorena Nadaf – Informatics Design (UCSF) • Dr. Angela DeMichele – Clinical Oncology (UPenn) • Don Berry & Kyle Wathen– Randomization Engine (MDACC) • John Churin– Software Lead Engineer (Tolven) • Ashwin Koleth – Software Development (Cyrus-XP) • John Koisch – Architecture (NCI) • Kathy Hajopoulos – Project Oversight (UCSF) • Nancy Roche – Project Oversight (SAIC) TRANSCEND development funded by the National Cancer Institute (NCI), Subcontract # 28XS197

17. 2TRANSCEND TEAM • Dr. Laura Esserman – I-SPY TRIAL, 2TRANSCEND PI (UCSF) • Dr. Michael Hogarth - 2TRANSCEND Technical Director (UC Davis) • Sarah Davis– 2TRANSCEND Project Manager (UCSF) • Meredith Buxton – I-SPY 2 Program Director (UCSF) • Dr. Angela DeMichele – Clinical Oncology (UPenn) • Don Berry & Kyle Wathen– Randomization Engine (MDACC) • John Churin– Software Lead Engineer (Tolven) • Ashwin Koleth – Software Development (Cyrus-XP) • Eve Shalley– Project Manager (NCI) • SantoshJoshi & CBIIT caCIS Team (NCI) • Ian Fore & CBIIT caTissue Team (NCI) • Paul Baumgarnter& CBIIT caAERS Team (NCI) • JuliKlemm& CBIIT caArray Team (NCI) • Shine Jacob & CBIIT caIntegrator Team (NCI) • Robert Shirley & CBIIT Architechture Team (NCI) 2TRANSCEND development funded by the National Cancer Institute (NCI), Agreement No. 12ST1002