# Presentation: 218538

## Oncology Biomarker Qualification Initiative: NCI-FDA-CMS Collaboration to Speed Development of Cancer Therapies

**Anna D. Barker, Ph.D.**
- Deputy Director, National Cancer Institute

- National Cancer Advisory Board Meeting
**June 14, 2006**

## Biomarkers: A Key to 21st Century Personalized Cancer Care 

- Image courtesy of *Science*, May 26, 2006

**Biomarkers: A Key to 21****st**** Century ****Personalized Cancer Care **

**“****The emerging use of cancer biomarkers may herald an era in which physicians no longer make treatment choices that are based on population-based statistics but rather on the specific characteristics of individual patients and their tumor.”**
*William S. Dalton **and Stephen H. Friend*
*Science;  May 26, 2006*

## The NCI-FDA Interagency Oncology Task Force (IOTF)

**IOTF was established in 2003 to enhance the efficiency of clinical research and the scientific evaluation of new cancer treatments**
**Examples of Key IOTF Focus Areas:**
**Establish joint training and fellowships**
**Discover and develop biomarkers for clinical benefit**
**Through use of caBIGTM, support standardization and organization of data reporting from clinical trials, and support electronic filings to accelerate regulatory reviews**
**Address specific regulatory barriers impeding cancer drug development**

## Process Enhancement – Exploratory INDs for small molecules; New GMP regulations for experimental agents
Biomarkers Qualification – The Oncology Biomarker Qualification Initiative
New Common Bioinformatics Platforms – Standards for clinical trials submissions; e-INDs; CRIX Project
Advanced Technologies – Critical Path Initiatives (nanotechnology and molecular diagnostics)
Training and Joint Appointments – Three training programs for PhDs and MDs

- Biomarkers Qualification – The Oncology Biomarker Qualification Initiative
- New Common Bioinformatics Platforms – Standards for clinical trials submissions; e-INDs; CRIX Project
- Advanced Technologies – Critical Path Initiatives (nanotechnology and molecular diagnostics)
- Training and Joint Appointments – Three training programs for PhDs and MDs

**The Interagency Oncology Task Force:  Examples of Initiatives**

## Focus Areas for the FDA’s Critical Path Initiative

- Developing biomarkers and new disease models
- Streamlining clinical trial
- Applying bioinformatics
- Enabling 21st century manufacturing
- Addressing urgent public health needs

## The Potential of Biomarkers Across the Discovery-Development and Delivery Continuum

- New _**target discovery**_ (understand underlying biology)
- Drug _**development**_ – markers of toxicity, metabolism, etc. - **pharmacogenomics**
_**Early detection**_ (broad or specific detection / corroboration of specific disease stage)
- Identify _**molecular basis of disease phenotypes**_
- Assessment of disease _**aggressiveness**_
_**Rational**_ choice of _**treatments**_ – selection for trials
_**Assessment**_ of treatment _**effectiveness**_
_**Prevention markers**_

## Gaps in the Current System Hinder Rapid Development and Adoption of Biomarkers in Clinical Care

**Technical: **Common standards are needed to evaluate biomarker technologies and compare experimental results
**Regulatory: **Qualified biomarkers are needed as assessment tools for use in FDA guidance for cancer drug development
**Economic: **Innovators are reluctant to conduct biomarker trials without evidence of widespread clinical applications; CMS needs evidence of clinical utility to inform reimbursement decisions
**Structural: **Biomarker-based studies require multi-disciplinary capability (genomics, proteomics, clinical biology, engineering, image computation, biomedical informatics, trial design, etc.) *

**Coordinated Effort Is Needed to Bridge the Gap Between ****Biomarker Discovery and Validation/Clinical Utility**

- * Source: Weissleder R. Molecular imaging in cancer. *Science* 312:1168-1171, 2006.

## OBQI: Unique HHS Partnership

**The Oncology Biomarkers Qualification Initiative (OBQI) is a new and innovative collaboration among ****NCI, FDA, and CMS designed to qualify biomarkers for use in clinical trials – and ultimately speed ****better agents to cancer patients*******

**OBQI: Unique HHS Partnership**

***Tri-partite MOU signed 01/23/2006**

## OBQI Coordinates Cross-HHS Goals for Biomarker Validation and Clinical Use

**OBQI**

**OBQI Coordinates Cross-HHS Goals for Biomarker Validation and Clinical Use**

- Develop biomarker technologies and validation protocols to improve detection, diagnosis, treatment, and prevention of cancer

- Make informed decisions about reimbursement of new or existing treatment regimens based on biomarker-guided knowledge

- Develop guidance for the use of biomarkers to facilitate cancer drug development

## OBQI will validate particular biomarkers to:
evaluate new, promising technologies in a manner that will facilitate and accelerate clinical trials
reduce the time and resources spent during the drug development process
improve the linkage between drug regulatory review and drug coverage
increase the safety and improve the efficacy of drug choices for cancer patients 

**evaluate new, promising technologies in a manner that will facilitate and accelerate clinical trials**
**reduce the time and resources spent during the drug development process**
**improve the linkage between drug regulatory review and drug coverage**
**increase the safety and improve the efficacy of drug choices for cancer patients**** **

**Goals of OBQI**

## Focus Areas for OBQI

**Cancer Imaging:**  Standardizing and evaluating imaging technologies
**Molecular Assays/Targeted Therapies:**  Developing scientific bases for diagnostic assays to enable personalized treatments
**Clinical Trials:**  New biomarker-driven clinical trials designs (including exploratory or “phase zero” trials)
**Data Mining:**  Pooling to share data and learning between trials

## The Role of Imaging-Based Biomarkers

**	****“****Imaging-based biomarkers can be used in all phases of the cancer drug development process, from target discovery and validation to the pivotal clinical trials that precede drug approval.” **
*Ralph Weissleder; Science; May 26, 2006*
**Validated biomarker imaging data could lead to:**
- Smaller clinical trials
- Earlier go/no-go decisions on compounds
- Accelerated regulatory review
- Shorter time to public availability
- Surrogate markers of efficacy

## FDG-PET exploits the reliance of tumor cells on glucose and glycolytic metabolism to image cancers (Warburg Effect, strong mechanistic rationale)

FDG-PET data can be assessed visually, or analyzed semi-quantitatively or quantitatively

FDG-PET is approved for use in the diagnosis, staging, and restaging of a variety of cancer types, and in these applications can significantly impact the clinical management of disease

In a number of clinical settings (e.g., NSCLC, esophageal cancer, lymphoma), FDG-PET can provide an early measure of response to treatment with approved therapies

With a few additional studies, FDG-PET could facilitate drug development and patient care by resulting in shorter phase II trials, accelerated approval in Phase III (full approval on evidence of clinical benefit and better patient care by stopping ineffective therapies

**FDG-PET data can be assessed visually, or analyzed semi-quantitatively or quantitatively**
**FDG-PET is approved for use in the diagnosis, staging, and restaging of a variety of cancer types, and in these applications can significantly impact the clinical management of disease**
**In a number of clinical settings (*****e.g*****., NSCLC, esophageal cancer, lymphoma), FDG-PET can provide an early measure of response to treatment with approved therapies**
**With a few additional studies, FDG-PET could facilitate drug development and patient care by resulting in shorter phase II trials, accelerated approval in Phase III (full approval on evidence of clinical benefit and better patient care by stopping ineffective therapies**

- Source: Kelloff *et al. *Clin Cancer Res 11: 2785–2808, 2005

**The Potential of FDG-PET**

## Oncology Biomarkers Qualification Initiative (OBQI) - Process

- Identify mutual priorities across the three partners
- Develop scientific rationale for candidate biomarker(s)
**Through the Foundation for the NIH:**
- Finalize the clinical question
- Collaborative development of the protocol with community experts
- Finalize protocol
- NIH Foundation seeks partners
- Trial performance

**Note: The OBQI serves as a pilot program for a trans-NIH biomarkers initiative **

## Project 1: 
FDG-PET Imaging in Non Hodgkin’s Lymphoma to Predict Tumor Response to Treatment

Project 2:  
FDG-PET Imaging in Non-Small Cell Lung Cancer to Predict Tumor Response to Treatment

- FDG-PET Imaging in Non Hodgkin’s Lymphoma to Predict Tumor Response to Treatment
**Project 2:  **
- FDG-PET Imaging in Non-Small Cell Lung Cancer to Predict Tumor Response to Treatment

**Initial OBQI Projects are Focused on Imaging-Based Biomarkers**

## Successful clinical management
Effective drugs
Existing clinical FDG-PET data for diagnosis and staging
Established treatment-response criteria that can be refined by FDG-PET

- Effective drugs
- Existing clinical FDG-PET data for diagnosis and staging
- Established treatment-response criteria that can be refined by FDG-PET

**Why FDG-PET in Non-Hodgkin’s Lymphoma?**

## Project 1:  FDG-PET Imaging in Non-Hodgkin’s Lymphoma to Predict Tumor Response to Treatment

**Objective **
- Refine CR criteria with FDG-PET imaging, establish predictive value of FDG-PET after two cycles of chemotherapy
- Provide data to support FDA and CMS decision-making - based on a common understanding of the roles of these types of assessments
**Clinical Trial Sites**
- Approximately 20 sites will be selected, to include Comprehensive Cancer Centers
- Approximately 400 patients
- Standard chemotherapy treatment
- Imaging at baseline, and after Cycles 2 and 6 of chemotherapy

**New Approach**

- Multiple clinical trial sites, all following the same protocol and sharing data in real time via caBIGTM

## Project 2:  FDG-PET Imaging Trial in Non-Small Cell Lung Cancer to Predict Tumor Response to Treatment

**Objective**
- Determine if FDG-PET scans can be used as surrogate markers of efficacy in lung cancer treatment
**Clinical Trial Sites**
- Approximately 15 sites will be selected, to include Comprehensive Cancer Centers
- Approximately 200 patients
- Standard, platinum-based therapy for lung cancer
- Three cycles of therapy,

**New Approach**

- Multiple clinical trial sites, all following the same protocol and sharing data in real time via caBIGTM

## OBQI: Next Steps

**NIH to finalize organizational structure for public-private partnership to fund biomarkers trials**
- To be announced in Summer 2006
**Select teams/sites for the first two OBQI trials**
- Potential sites currently being considered and will be selected and funded in Fall 2006
**Determine next OBQI trials**
- Expert group to identify next trials in Fall 2006

## Biomarkers Will Ultimately Enable Development of Personalized Cancer Care

**Patient Information**

**Molecular, Imaging, and Clinical Knowledge**

**Biomarkers Will Ultimately Enable Development of Personalized Cancer Care**