Workshop on Product Development for CNS Metastases

Metastatic brain cancer can result from several types of primary cancers including but not limited to breast, kidney, lung, and skin cancer (melanoma). Brain and central nervous system (CNS) metastases represent late-stage cancer and are always a serious, if not a life-threatening diagnosis.

More than 80% of cancers have been associated with the ability to metastasize to the brain.
(Journal of the National Cancer Institute – JNCI) These include:

• Lung – (25-50%)
• Breast (15-20%)
• Melanoma (10%)
• Renal (5-10%)
• Colorectal (1-5%)

Studies cite that anywhere from 6-28% of cancer patients develop brain metastases. There are too few treatments for cancer patients with brain metastases and also too few clinical trials aimed at developing new treatments. Increased efforts to develop therapeutic products are needed to address this unmet medical need and ultimately help patients. Barriers to product development for CNS metastases include lack of clinical trials specific for this population, exclusion of patients with brain metastases from clinical trials, and lack of standardized response assessments.

In light of all this, the Food and Drug Administration and the National Brain Tumor Society, joined by a strong coalition of patient advocacy and research organizations, collaborated to host a workshop on March 22, 2019, at the FDA campus, with the intent to provide an open forum to discuss key challenges including clinical trial accrual, study design, and endpoint selection for brain metastases research and treatment discovery.

This workshop has generated results, criteria, documentation, and awareness for the challenges of brain tumor mets patients. SEE the SIDEBAR for materials and resources related to brain and CNS metastases. Also, view the pre-workshop video segments featuring key researchers, medical professionals, and clinicians that highlight key sessions of the workshop.

**The coalition includes ABC2, ABTA, Friends of Cancer Research, KCCure, LUNGevity, MBCA, MRA, RANO and SNO

• There is enthusiasm for including patients with CNS metastases broadly in clinical trials, and having opportunities for all such patients is a major source of hope for them.
• There is general consensus that these patients can be more broadly included in trials without compromising safety or trial design, and many past assumptions need to be challenged.
• There is strong research identifying potential targets for drugs.
• Additional guidance from FDA would be welcome.
• There is recognition that more needs to be done to include in trials patients with leptomeningeal disease.
• There is a need to develop trials and drugs that specifically target brain metastases.
• Developing new innovative endpoints and selection of endpoints for trials involving brain metastases patients remains a major challenge, and ultimately might depend on the trial, drug, cohort of patients, and other specific facts. Appropriate endpoints may differ between early and late clinical development.
• Imaging is one area where more work needs to be done to help make radiographic endpoints more feasible in trials with brain metastases patients. This will include refinement and adoption of RANO brain metastases guidelines, as well as the development of standards for acquiring imaging data in trials using new and advanced imaging methods.

March 22, 2019
8:00am to 4:00pm
FDA White Oak Campus Building 31, Great Room

8:00 – 8:30AM
Registration

8:30 – 8:35AM
Opening Remarks:

David Arons, JD, National Brain Tumor Society
Richard Pazdur, MD, US Food and Drug Administration
Wendy Selig, MSJ, WSCollaborative

8:35 – 8:45AM
Presenting the Challenge
Joohee Sul, MD, Workshop Co-Chair, US Food and Drug Administration
Patrick Wen, MD, Workshop Co- Chair, Dana Farber Cancer Institute

8:45 – 9:45AM
Session I: Defining the Problem of CNS Metastases
Laleh Amiri-Kordestani, MD, Co-Chair, US Food and Drug Administration
Greg Riely, MD, Co-Chair, Memorial Sloan Kettering Cancer Center

Discussant Presentation:
Clinical Management of CNS Metastasis, 2019: Current Strategies, Investigations, and Key Challenges
Mike Davies, MD, MD Anderson Cancer Center

Panel:
Laleh Amiri-Kordestani, MD, & Greg Riely, MD, Moderators
Manmeet Ahluwalia, MD, Cleveland Clinic
Mike Davies, MD, MD Anderson Cancer Center
Victoria Ebiana, MD, Merck
Derrick Queen, Patient
Luke Walker, MD, Seattle Genetics

9:45 – 11:00AM
Session II: Key Issues for Clinical Development for Brain Mets

Nancy Lin, Co-Chair, Dana Farber Cancer Institute
Chana Weinstock, Co-Chair, US Food and Drug Administration

Discussant Presentations:

• Identifying Targets for Brain Mets Clinical Studies
  Priscilla Brastianos, Massachusetts General Hospital
• Selecting Drug Candidates for Brain Mets
  Nancy Lin, Dana Farber Cancer Institute
• Issues with Conducting Brain Mets Clinical Trials
  Kim Margolin, City of Hope
• Standardizing Brain Mets Response Assessment
  Ben Ellingson, University of California, Los Angeles

Q&A

Session Recap:  Chana Weinstock, US Food and Drug Administration

11:00 – 11:15AM
Break

11:15 – 2:30PM
Session III: Clinical Benefit in Patients with Brain Mets

Carey Anders, Co-Chair, Duke University
Tatiana Prowell, Co-Chair, US Food and Drug Administration

11:15-12:30PM
Discussant Presentations:

• Regulatory Definition of “Clinical Benefit”
  Paul Kluetz, US Food and Drug Administration

Designing an Endpoints Framework for CNS Metastases
Carey Anders, Moderator

Panel: Terri Armstrong, National Cancer Institute
Shelly Engfer-Triebenbach, Patient
Chitkala Kalidas, Bayer Pharmaceuticals
Ben Levy, Sibley Memorial Hospital
Jeff Wefel, MD Anderson Cancer Center
Arvin Yang, Bristol-Myers Squibb

Q&A 

Panel Recap: Carey Anders, Duke University

12:30 – 1:00PM
Lunch

1:00 – 2:30PM
Discussant Presentations:

• Regulatory Challenges for CNS Metastases
  Shanthi Marur, US Food and Drug Administration 

Rethinking Trial Designs for Stimulating Product Development for CNS Metastases
Tatiana Prowell, Moderator

Panel: Michael Atkins, Georgetown University
Kim Blackwell, Eli Lilly and Company
Vinai Gondi, Northwestern Medicine
Pallavi Mishra-Kalyani, US Food and Drug Administration
Hussein Tawbi, MD Anderson Cancer Center
Lynda Weatherby, Patient

Q&A

Panel Recap: Tatiana Prowell, US Food and Drug Administration

2:30 – 3:30PM
Session IV: Therapy Development: Challenges & Opportunities

Joohee Sul, Co-Chair, US Food and Drug Administration
Patrick Wen, Co-Chair, Dana Farber Cancer Institute

Defining Strategies to Advance Product Development

Panel: Lauren Abrey, Novartis
Caroline Chung, MD Anderson Cancer Center
Nancy Lin, Dana Farber Cancer Institute
Kim Margolin, City of Hope
Tatiana Prowell, US Food and Drug Administration
Greg Riely, Memorial Sloan Kettering Cancer Center
Peggy Zuckerman, Patient

Q&A

3:30 – 3:40PM
Overview of the American Brain Tumor Association’s Metastatic Brain Tumor Initiative

Ralph DeVitto, American Brain Tumor Association
Nicole Willmarth, American Brain Tumor Association

3:40 – 4:00PM
Summary & Next Steps

David Arons, National Brain Tumor Society
Joohee Sul, US Food and Drug Administration
Patrick Wen, Dana Farber Cancer Institute

 4:00PM
Adjourn