# Presentation: 473188

## I-SPY 1 and I-SPY 2 Trial ProcessTRANSCEND STAKEHOLDERS KICKOFF MEETING October 30, 2008

## What Is I-SPY 2

- Phase 2 adaptive design clinical trial program for the neoadjuvant setting in breast cancer
- A process for rapid, focused clinical development of paired oncologic therapies and biomarkers
- Appropriate for NCI/FDA critical path initiative
- High interest across NCI, FDA, academic and industry research community
- High potential for accelerating development of new therapies and benefiting patients
- Research process is highly collaborative-across all sectors—ideal for Biomarkers Consortium

## I-SPY 2 Core Project Team and Working Group*

- Janet Woodcock, MD (FDA), Chair, *Ex Officio*
- Gary Kelloff, MD (NCI), Co-Chair
- *Laura Esserman, MD, MBA (UCSF, PI), Co-Chair
- *Caroline Sigman, PhD (CCSA), Program Manager, CSC
- *Don Berry, PhD (MDACC)
- Nola Hylton, PhD (UCSF)
- Steve Gutman, MD, MBA (FDA, OIVD)
- Subha Madhavan, PhD (Georgetown University)
- Joe Gray, PhD (LBNL)
- Lajos Pusztai, MD, PhD (MDACC)
- Jane Perlmutter, PhD (Advocate)
- *Donya Bagheri, MS, DABT (CCSA), Project Manager
*Ad Hoc* David Lee, MPA (FNIH)
- *Meredith Buxton, MPhil, MPH (UCSF), Research Program Manager
- *Sarah Davis, MS (UCSF)
- *Dan Milgram (CCSA)
- *Angela DeMichele, MD (University of Pennsylvania)
- *Ann Staten, RD (FDA)

**I-SPY 2 Core Project Team and Working Group***

## Overview

-  I-SPY TRIAL
-  Informatics Tools in I-SPY 1
-  Introduction to I-SPY 2
-  Statistical Overview of I-SPY 2 Trial Design
-  Use of Biomarkers in I-SPY 2
-  Selection of Agents in I-SPY 2
-  Organization and Milestones

## 		Imaging

- 	Serial studies to
- 	Predict
- 	Your
- 		Therapeutic
- 		Response with
- 		Imaging
- 		And
- 	   moLecular analysis

**C****ALGB,**** I****NTER****S****PORE,**** A****CRIN,**** N****CICB**

***I SPY WITH MY LITTLE EYE . . . . . . . A BIO-MARKER BEGIN-ING WITH X***
***. . . .***

- CALGB 150007/150012 & ACRIN 6657

- Serum markers: 1470 samples from 209 patients; Analysis by 7 Laboratories

## I-SPY 1 Endpoints

- Early endpoint: pathologic complete response
- pCR:		 27% (56/210)
- no pCR:     73% (154/210)
- Primary Endpoint:  3 year DFS

## I-SPY 1 pCR by Biomarkers

|  | ER+ | ER- |  |
| --- | --- | --- | --- |
| HER2+ | 28% | 48% | 37% |
| HER2- | 10% | 36% | 18% |
|  | 15% | 41% | 25% |

- *Excluding Patients who received Herceptin (n=16)
- Effect of ER– over ER+: 26% (p=0.0002)
- Effect of HER2+ over HER2–: 19% (p=0.009)
- Interaction (p=0.29)

- Pathologic Complete Response

## Molecular Predictors of pathologic Complete Response (pCR) 

| Predictor | P Value |
| --- | --- |
| NKI 70 genes (Van ‘t Veer) | 0.007 |
| GHI Recurrence Score (Paik) | 0.007 |
| T-FAC 30 gene set (MDACC) | 0.02 |
| TP53 (Perou) | 0.01 |
| Molecular Subtypes (Sorlie) | 0.02 |
| ER, Phospho ER | (-) 0.0002 |
| Her-2, Phospho Her-2 | 0.009 |
| MRI Volume | significant |

## I-SPY 1 Implications of pCR

- With a mean follow up of 3.1 years,
- Chance of Distant Recurrence if pCR:		 8%
- Chance of Distant Recurrence if no pCR:	19%

## Implications

- Neoadjuvant treatment provides the right setting to rapidly optimize regimens and improve response
- I-SPY TRIAL data set is an important resource to help us validate and generate hypotheses about resistance and biology in locally advanced breast cancer
- Great platform for
- developing and validating biomarkers of response
- learning which agents have greatest likelihood for improving response

**Implications**

## I-SPY TRIAL TOOLS

## Founding Principles of the I-SPY Trial

- Investigators agreed to sharing data  and biologic materials
- Data sharing/Publication guidelines adopted by all participating investigators
- Data to be released after completion of trial and accessible to the community
- Adherence to data standards
- Use of common data elements

## Tools to support Re-engineered Process for Correlative Science Trials

- _I-SPY Approach_
- Data Integration
- across multiple platforms
- From tissue specimen
- 	to results
- Tracking quality of specimens, assays
- Democratized Access to Data
- All investigators have access
- Leverage common tools
- caIMAGE
- caINTEGRATOR
- caARRAY
- Data already at NCI, ready to be shared

- _Current standard_
- Each lab has their own data
- Tracking progress challenging
- Comparison of data across platforms challenging
- One statistician, PI has control over  analyses

## Tissue Distribution Schema

- Paraffin

**2 Frozen **
**Cores**

**Initial H&E**

- IHC

- FISH

**Proteomics**

**RNA**

**1 Frozen **
**Core**

**1 Frozen **
**Core**

**Storage**

**Initial H&E**

- RNA

**Storage**

**DNA**

**Gene Chip**
**For P53**

- CGH

**UNC**:
**Dressler Lab**

**UCSF**

**Georgetown:**
**Liotta/Petricoin Lab**

**Tumor **
**Enriched**

**Core Remainder**

**UCSF:**
**Haqq**** ****Lab**

**Gene**
** ****Expression**

**UNC:**
**Perou Lab**

**UCSF:**
**Gray Lab**

**UNC:**
**Carey(Dorsey)  Lab**

**Check for **
**Tumor Presence**

**Check for **
**Tumor Presence**

**30%**

**70%**

**Her2 Protein**
**Over expression**

**Her2, TopoII **
**Gene Amplification**

**Gene **
**Expression**

**Tissue Distribution Schema**

## Tools for I-SPY 1 at a glance

- Ready when study opened
- LabTrak
- ACRIN
- Image archiving
- CALGB database
- Data sharing agreement

- Over the course of the trial
- Web Portal
- PLONE
- Quality Portal
- caINTEGRATOR
- batch uploads
- NCIA
- Oracle Clinical
- Pathology review
- Centra for distributed “lab meetings”
- User’s Guide

## I-SPY TRIAL Web Portal

- caINTEGRATOR

**I-SPY TRIAL Web Portal**

## Slide 18

## Quality Indicator (QI) Portal

- The QI Portal will allow I-SPY users:
- 1. To submit sample quality indicators, e.g. Sample, DNA and RNA  quality indicator data.
- 2. To search all the quality indicators that have been submitted to the database.
- Password-protected user access

**http://caqiportal.nci.nih.gov**

## QI Submission

- This page allows user to submit        general information including sample, frozen core, paraffin core, DNA and RNA information on a single sample.

## QI Retrieval

- Simple and advanced search modes are available.
- Search for quality data on specific samples of interest.

## I-SPY Pathology Data Collection Tool

-  A useful remote data capture tool for I-SPY, now proposed for other CALGB studies:
- e.g., proposed for use in CALGB 40601 by Baljit Singh, MD
-  Allows for direct data entry
-  Illustrated here, the general menu:
- each row = an enrolled patient
-  each column = a different pathology data form

## I-SPY Pathology Data Collection Tool

**I-SPY Pathology Data Collection Tool**

-  An example of a section from the data entry form featuring:
- User-friendly format
- Drop down menu choices where applicable
- In-form scripting (e.g., tumor stage can be calculated automatically upon data entry)

## File Sharing – slide images and tissue logs, meetings

## I-SPY: Data analysis portal

## Screenshots from I-SPY data portal

**Screenshots from I-SPY data portal**

## Clinical Report based on MRI Morphologic pattern

## Correlate data from different platforms

## User’s Guide gives clear and simple directions for conducting complex analyses.

This will be particularly important when the data set is released to the research community next year

- This will be particularly important when the data set is released to the research community next year

## Inside the User’s Guide

**Inside the User’s Guide**

## Background Summary for I-SPY 2

- Surgery

- Anthracycline

- Taxane

**I-SPY 1:**
- (2002–Present)

-  I-SPY 1 evaluated biomarkers and imaging for predicting	response to standard neoadjuvant chemotherapy
-  I-SPY 2 will evaluate Phase 2 drugs in combination with	standard chemotherapy in a neoadjuvant setting
-  I-SPY 2 will use biomarkers to stratify patients based on	their predicted likelihood of response to treatment
-  I-SPY 2 will use imaging to measure response

## Biomarkers in I-SPY 2

- When a drug leaves the trial, we learn the probability of success to predict response for
- Established/Approved Biomarkers
- IDE Biomarkers
- Qualifying Biomarkers
- Exploratory Biomarkers (discovery of new markers of response prediction)

## Biomarkers

- Established/Approved/IDE Biomarkers– for Stratification
- IHC and FISH for ER, PR, and HER2
- MammaPrint from 44K microarray
- MRI volume
- HER2 and pHER2 by RPMA, mRNA HER2 by 44K microarray
- Qualifying Biomarker Definition
- Performed under CLIA conditions
- Shows promise for predicting response to standard agents or novel therapies
- Exploratory Biomarker Definition
- Reflect next generation technology
- Purpose is to enable trial to evolve and keep pace with technology

## Additional Biomarker Examples

_**Qualifying Biomarkers**_
- Panomics assay for drug and prognostic predictors
- RPMA pathway markers for stratification and prediction of response
- RCB predictor of response
_**Exploratory Biomarkers**_**:**
- DNA methylation
- Exon capture sequencing
- RPMA pathway discovery and profiling
- Copy number and SNP chip
- Pharmacogenomics (germline SNP)
- miRNA
- Panomics – 2nd generation predictors
- Circulating tumor cells
- MRI SER segmentation
- Circulating Tumor Cells
- Other drug specific markers

## I-SPY 2  Adaptive Trial Schema

- Taxane
- ±
- New Agent C, D, or E

- AC

- HER2 (+)

- HER2
- (–)

_**Randomized**_

**I-SPY 2  Adaptive Trial Schema**

- Taxane & Herceptin
-  ±
- New Agent A, B, or C

- AC

_**Randomized**_

- Surgery

- Surgery

- Stratifying
- Biomarkers

- Biopsy
- used for
- Biomarkers

## Goals of I-SPY 2

- Identify which biomarker signatures predict response to specific drug combinations
- Model relationship between baseline and longitudinal markers (depending on therapy) to predict pCR
- Confirm observations within trial – at least partially
- Better treatment of patients in trial
- Graduate drugs and biomarkers to smaller, more focused Phase 3

## I-SPY 2 Adaptive Design Trial Process

-  Adaptive design allows efficient learning for	changing/adding new agents over the course	of the trial
-  Uses biomarkers, imaging and pathology    		endpoints to drive change
-  Validates, tests, and qualifies biomarkers as 			we test new agents
-  Uses a collaborative multi-disciplinary team approach

## I-SPY 2: Adaptive Phase 2Neoadjuvant Breast Cancer Process

- Moderate to high-risk breast cancer
- Baseline biopsy: assess biomarkers
- Primary endpoint: pCR
- Model pCR based on interim MRIs
- Many drugs added to standard treatment (control)

**On Study**

- MRI

- MRI

- MRI
- Blood

**Surgery**

- Biopsy
- Blood

- MRI
- Biopsy

- Tissue

**Taxane +/–New Drug**
**(12 weekly cycles)**

**AC**
**(4 cycles)**

## Overview of I-SPY 2 Design

- Standard control (taxane-based)
- Balance randomization to new drugs initially
- Build predictive index for each therapy/biomarker combination
- Adaptively randomize
- Evaluate many drugs & combinations
-  Successes graduate to Phase 3
-  Underperformers dropped for futility

**On Study**

- MRI

- MRI

- MRI
- Blood

**Surgery**

- Biopsy
- Blood

- MRI
- Biopsy

- Tissue

**Taxane +/–New Drug**
**(12 weekly cycles)**

**AC**
**(4 cycles)**

## Patient Strata

**Patient Strata**

- MP: MammaPrint High 1 or High 2
- HR+: Hormone Receptor+: Either ER+ or PR+

## Biomarker signatures (2^8 combinations of bins): B1, B2, ..., B255
However, restrict to marketable signatures, numbering approximately 20
 Graduate drugs/signatures from trial:
 Based on effectiveness
 Based on prevalence

- However, restrict to marketable signatures, numbering approximately 20
-  Graduate drugs/signatures from trial:
-  Based on effectiveness
-  Based on prevalence

**Minimal set:**

**Patient Strata (8 bins)**

## Experimental Therapies: T1,..., Tk 

-  Ti sample size Ni: 20 < Ni < 120
-  Patient enters in trial, falls in bin
-  We calculate Pi = P(Ti >> control | data, bin)
-  Modeling across bins
-  Assignment proportions 1:P1:P2: ... :Pk

## Dropping, Graduating Ti 

-  For each possible biomarker signature B, 			calculate		Qi = P(Ti >> control | data, B)
-  If Qi < 10% for all signatures then Ti is dropped		from trial
-  If Qi > 95% for some signature then Ti graduates
-  We provide probability Phase 3 success for each		possible signature, including the one on 			diploma

## I-SPY 2 Adaptive Trial OutlinePhase 2 Neoadjuvant

- Enroll ~20 patients per month
- Participating Sites: 15–20 across US, possibly Europe and Canada

**On Study**

- MRI

- MRI

- MRI
- Blood

**Surgery**

- Biopsy
- Blood

- MRI
- Biopsy

- Tissue

**Taxane +/–New Drug**
**(12 weekly cycles)**

**AC **
**(4 cycles)**

**I-SPY 2 Adaptive Trial Outline****Phase 2 Neoadjuvant**

**Notes:**
Don to Laura

## I-SPY 2 Adaptive Trial Schema

- Taxane

- Taxane + New Agent A

- Taxane + New Agent D

- Taxane + New Agent E

- AC

- HER 2
- (–)

- _Randomized_

**I-SPY 2 Adaptive Trial Schema**

**Learn, adapt from each patient as we go along**

- Surgery

- Biopsy
- used for
- Biomarkers

## I-SPY 2 Adaptive Trial: 

- Taxane + New Agent C

- Pt is On Study

- Taxane + Herceptin

- Taxane +  Herceptin + New Agent B

- Taxane + Herceptin + New Agent C

- Taxane

- Taxane + New Agent D

- Taxane + New Agent E

- AC

-  AC

- HER 2 (+)

- HER 2
- (–)

- _Randomized_

- _Randomized_

- Surgery

- Surgery

**I-SPY 2 Adaptive Trial: **
**Learn, Drop, Graduate, and Replace Agents Over Time**

- Taxane +  Herceptin + New Agent F

- Taxane +
- New Agent GH

- Taxane +  New Agent F

## Critical Steps for Agents and Biomarkers

** ****Identify biomarkers for evaluation in study****—those for 1) initial patient treatment assignment****, 2) development during study, 3) exploratory**
- Pre-IDE meeting with FDA September 4, 2008
- Agreement on IDE’s required to initiate study as planned
- Agreement on study plan for additional biomarkers
** ****Identify agents for testing in I-SPY 2**
- Prepare list of candidate agents for evaluation
- Develop selection and prioritization process for agents
- Identify initial 1st and 2nd tier candidate agents
- Pre-IND meeting with FDA planned for fall 2008
- Submission of Master IND planned for late 2008
- Develop procedure for graduating and dropping agents

## I-SPY 2 Ready Agents - (Tier 1)

- Agents where there is promise to improve upon the response to standard chemotherapy
- Agents where there is Phase 1 data for a novel agent in combination with Taxane
- In any cancer setting

## I-SPY 2 Almost Ready Agents (Tier 2)

- Novel agents or combinations of agents that have promise to improve the response to taxane based therapy
- Phase 1 data on individual agents available but not in combination or with Taxane
- Phase 1 sites identified (among I-SPY TRIAL sites) to participate, lead Phase 1 studies in preparation

## Slide 50

## I-SPY 2 Drug Target Pathways

**Survival, Metabolism**

**Activated**
**AKT**

- p53

**Cell Cycle Arrest**
**Apoptosis**

**PIP****3**

**PIP****2**

**Angiogenesis**

- Caspase-2

- HER2

- IGFR

- EGFR

- VEGF

- FasL

- TIE

- Angiopoietin-1

**Tumor Cell**

**Endothelial Cell**

- TRAIL

- mito

**RAS/RAF**

- MEK

- MET

**I-SPY 2 Drug Target Pathways**

**Growth, Proliferation**

**DNA Damage**

**Protein Damage**

- AC Chemo

**DNA Repair**

- MDM2

**Nucleus**

- Taxanes

**Cytoskeletal Damage**

## Priority Pathways

- HER2 (HSP90, HER2, HER3)
- IGFR
- PI3K
- Macrophage
- AKT
- AKT + MAPK, ERBB2, or PI3K+MEK inhibitors
- Death Receptor
- c-MET
- mTOR + X
- Angiogenesis + X

## I-SPY 2 Agent Evaluation Process

- Generated list of potential agents across many targeted pathways
- Invited interested Industry partners to review list
- Pharmaceutical Industry Focus Group (met 9/19/08)
- Input on selection & prioritization of drugs and classes
- Input on the various signatures to be used in the study design
- Willingness to commit drugs to the study
- 20 agents identified to date

## Priority Agents for Discussion: HER2+ 

| Target | Drug | Manufacturer | Single
Agent
Phase 1 | Single Agent
Phase 2 | Taxanes +
Agent Phase 1/2 | Evaluated in 
Breast 
Cancer | Biomarker
for Cohort
Identification
Drug Effect  | Issues |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| For Evaluation in HER2+ Patients  |  |  |  |  |  |  |  |   |
| HER2
Inhibitors | Pertuzumab (2C4) | Genentech | √ | √ | √ | ? | √ |  |
|  | Lapatanib +
Pazopanib | GSK | √ | Combo in progress | √ | Combo in progress | √ |  |
|   | T-DM-1 | Genentech | √ | In progress | ? |   | ? |   |
| IGFR
Inhibitors | AMG 479 | Amgen | √ | √ |  | In progress | √ |  |
|  | AI2 (IMC-A12) | Imclone | √ | In progress |  | In progress | √ |  |
|  | CP-751871 | Pfizer | √ | In progress | In progress | In progress | √ |  |
|  | SCH717454 | Schering Plough | ? | In progress (w/ chemo-therapy) |  |  | √ |  |
| PanErbB
inhibitor  | HKI-272 (Neratinib) | Wyeth | √ |  | In progress | In progress | √ |  |
| Hsp90
Inhibitors | Alvespimycin | Kosan/Bristol Myers  | √ | In progress? | In progress? | √ | ? |  |
|  | Tanespimycin (KOS-953) | Kosan/Bristol Myers  | √ | In progress | In progress | √ | ? |  |

## Priority Agents for Discussion: Non HER2+ Drugs

| Target | Drug | Manufacturer |  | Single
Agent
Phase 1 | Single Agent
Phase 2 | Taxanes +
Agent Phase
1/2 | Evaluated
in
Breast
Cancer | Biomarker
for Cohort
Identification
Drug Effect  | Issues |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| For Evaluation in HER2– or HER2 + Patients  |  |  |  |  |  |  |  |  |  |
| Angio-genesis
Inhibitors | Pazopanib | GSK | √ |  | √ | √ | √ | √ |  |
|  | AMG 386
(angiopoietin
neutralizing) | Amgen |  |  |  | √ |  | √ |  |
|  | AMG 706 (VEGFr
TKI Inhibitor) +Paclitaxel | Amgen | √ |  | √ | In progress | In progress | √ |   |
| Multi-kinase
Inhibitors | Bosutinib (SKI 606) | Wyeth | √ |  | √ | In progress? |   | √ |  |
| PI3K
Inhibitors | PI3K inhibitor | GSK | Planned
for Aug.
2008 |  |   |   |   | √ |   |

## Priority Agents for Discussion (continued)

| Target | Drug | Manufacturer | Single
Agent
Phase 1 | Single Agent
Phase 2 | Taxanes +
Agent Phase
1/2 | Evaluated
in
Breast
Cancer | Biomarker
for Cohort
Identification
Drug Effect  | Issues |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| For Evaluation in HER2– or HER2+ Patients (continued) |  |  |  |  |  |  |  |  |

| mTOR
Inhibitors | Temsirolimus (CCI779)(+ evacizumab) | Wyeth | √ | √ | In progress | √ | √ |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| PARP
Inhibitors | ABT888 | Abbott | √ |  | √? In progress | In progress | √ |  |
|   | KU-59436/AZD2281 | KuDOS/
AstraZeneca | √ |   | In progress | √ | √ |   |
| cMET
Inhibitors | AMG102 | Amgen | √ | √ |  |  | √ |  |
| Apo/TRAIL
Agonists | AMG 655 (mAb) | Amgen/
Genentech | √ |   | √? In progress |   | √ |   |

## Industry Focus Group Meeting Summary

- Industry enthusiastic about trial process, willing to participate and nominate agents
- Interested in biomarkers that segment prognosis
- In agreement with transparent process for choosing agents
- In agreement with testing agents by class
- Next steps
- Clarify data sharing process
- Pre-IND meeting with FDA, refine registration path

## Data Protection and Sharing

- Data on agents and biomarkers shared per general guidelines of The Biomarker Consortium and specific procedures established for I-SPY 2 study
- Device manufacturers may maintain IDE’s and use data generated in study to support FDA approval/clearance of biomarker assay
- Master IND maintains drug-specific proprietary data
- Data generated in I-SPY 2 may be used to support focused Phase 3 studies of drug/drug class or other further clinical evaluation of drug/drug class

**Notes:**
?? Do we want this in??

## I-SPY 2 Process Offers

- Network of Physicians committed to Neoadjuvant Chemotherapy
- 1st trial where Phase 2 agents can be tried in NAC setting
- Enables smaller, better informed Phase 3 Trials with companion biomarkers
- Faster throughput of agents without the development of a new protocol
- Opportunity to learn which subset of patients are most responsive
- Learn about efficacy of “classes” of agents not just specific drugs

**Notes:**
Laura to Dr. Kelloff

## I-SPY 2 Team

**Executive Committee**

- Trial Design

- Informatics

- Drug Selection

- Biomarker Devices

- Imaging

- Intellectual Property

- Project Management

- Trial Implementation

**Notes:**
Dr. Kelloff

## I-SPY 2 Trial Implementation Timeline

**I-SPY 2 Trial Implementation Timeline**

**Trial Starts**

**Trial Ends**

## I-SPY 2 Drug Selection Timeline

- Industry Advisory Meeting

- IND Submission

- Fundraising Completed

**I-SPY 2 Drug Selection Timeline**

## Major Milestones

| FDA Pre-IDE meeting
 | September 4 2008 |
| --- | --- |
| Focus Group with Pharma Leaders
 | September 19, 2008 |
| Informatics Infrastructure Building Award: TRANSEND (Adaptive Trial Bundle Award) | September 30, 2008 |
| FDA Pre-IND meeting | November 2008 |
| Submission of Master IND | December 2008 |
| Protocol Complete | December 15, 2008 |
| Sites selected | January 15, 2009 |
| Pharma Contracts Signed | March 2009 |
| Sites Trained, Qualified, Tools Installed | May-July 2009 |
| Trial Ready to send to CHRs | June 2009 |

## Tools to TRANSCEND from I-SPY 1  2

- Paper CRFs
- Lab Trak specimen shipping and tracking
- Tissue and biomarker quality a stand alone application

- Automated CRFs from clinical care observations (point of care)
- caTISSUE for life cycle of capture, storage, transformation, results
- Quality of biomarker an integral part of specimen storage in caTISSUE

## TRANSCEND  CRF’s I-SPY 1  2

- I-SPY 1
- Paper CRF completed
- 	Faxed to CALGB
- 	Scanned
- 	 transferred to electronic database
- 1 year ago, CRFs could be filled in an electronic PDF and electronically sent to CALGB

- I-SPY 2 (RING OF CARE)
- Clinician captures clinical observations (EHR “wizard”)
- 	CRF populated automatically;
- 	Study Coordinator, patient can enter additional data as needed
- 	Electronic transfer to  CCSA, caINTEGRATOR. etc

## TRANSCEND BiospecimensI-SPY 1  I-SPY 2

- I-SPY 1 Specimens
- Specimen IDs issued in Labtrak
-  Specimen Shipped in Labtrak
-  Specimen Sub-sampled in Labtrak
- Only CALGB member sites were able to use Labtrak for the first 2 years of the study.
- Labtrak unable to Ship sub-sampled specimens

- I-SPY 2 Specimens
- Specimen IDs issued in caTISSUE
- Specimen Shipped in caTISSUE
-  Specimen Sub-sampled in caTISSUE
-  Sub-samples Shipped in caTISSUE
-  Results reported using caTISSUE #
- - Specimen information in one system, accessible to all study sites

## TRANSCEND Biomarker QualityI-SPY 1  I-SPY 2

- I-SPY 1
- Specimen Quality entered in QI Portal by user
- Assay Quality data tracked in QI Portal
- Specimen data from Labtrak had to be hand entered into QI Portal before Assay data could be entered
- Quality data only accessible in QI Portal

- I-SPY 2
- Specimen Quality tracked in caTISSUE
- Assay Quality data tracked in caTISSUE
- Specimen data doesn’t have to be re-entered into a new database by user
- Assay Quality data easily transferred  to caINTEGRATOR

## NEOADJUVANT I-SPY 2 PROCESS 

**NEOADJUVANT I-SPY 2 PROCESS **

**Potential to Accelerate the Path to Personalized Treatment**
**Potential to develop and test an integrated suite of caBIG tools **