The
Biomarkers Consortium, a unique public-private partnership that
includes the U.S. Food and Drug Administration (FDA), the National
Institutes of Health (NIH), and major pharmaceutical companies, led by
the Foundation for the National Institutes of Health (FNIH), today
announced the launch of a highly anticipated clinical trial to help
screen promising new drugs being developed for women with high risk,
fast-growing breast cancers—women for whom an improvement over standard
treatment could dramatically change the odds of survival.
“Developing individualized medicines
needs a solution bigger than any one group can generate. The Biomarkers
Consortium is a public-private collaboration of scores of organizations
working together to achieve this critical mission. It is a model for the
future and FDA is proud to be a founding member.”
The
I-SPY 2 trial will employ a groundbreaking clinical trial model that
uses genetic or biological markers (“biomarkers”) from individual
patients’ tumors to screen promising new treatments, identifying which
treatments are most effective in specific types of patients. In
addition, an innovative adaptive trial design will enable researchers to
use early data from one set of patients to guide decisions about which
treatments might be more useful for patients later in the trial, and
eliminate ineffective treatments more quickly.
“I-SPY 2 promises to leverage convergence of progress on a number of
research fronts to speed the evaluation of promising new breast cancer
drugs using molecular cancer biomarkers to identify those agents that
are effective in specific subpopulations of breast cancer patients,”
said Anna D. Barker Ph.D., Deputy Director, National Cancer Institute,
and Co-Chair of The Biomarkers Consortium Cancer Steering Committee.
“This will allow us to finally design advanced, smaller and less
expensive Phase III trials that test the right drugs in the right
patients.”
The large-scale trial involves a unique collaboration by scientists from
the National Cancer Institute (NCI), FDA, and nearly 20 major cancer
research centers across the country. Study results will be made broadly
available to the entire cancer research and development community.
“The I-SPY 2 trial explores a whole new way to rapidly screen new cancer
treatments and match the therapy to specific markers,” said Janet
Woodcock, M.D., Director, Center for Drug Evaluation and Research at the
U.S. Food and Drug Administration. “Developing individualized medicines
needs a solution bigger than any one group can generate. The Biomarkers
Consortium is a public-private collaboration of scores of organizations
working together to achieve this critical mission. It is a model for the
future and FDA is proud to be a founding member.”
I-SPY 2 has the potential to significantly reduce the cost of drug
development and speed the process of screening drugs with the goal of
bringing safe and effective new drugs to market more efficiently.
Currently, it takes over $1 billion, 12 to 15 years, and thousands of
patient volunteers to get a single drug to market. I-SPY 2 was developed
to allow the activity of drugs to be assessed much earlier in the
research process, potentially enabling drugs to be developed and
approved using fewer patients, less time and far fewer resources. The
goal is to shave several years and hundreds of millions of dollars off
the current process.
The I-SPY 2 trial will focus on treatment in the neoadjuvant therapy
setting, in which chemotherapy is given to patients to reduce tumor size
before surgery. All patients will receive the current standard of care
and most participants will receive one investigational drug. A
distinctive feature of the trial is that it will screen multiple drugs
from multiple companies—up to 12 different cancer drugs over the course
of the trial. In order to do this, FNIH received a master
Investigational New Drug (IND) approval from the FDA—which allows the
I-SPY 2 TRIAL team to graduate, drop and add drugs seamlessly throughout
the course of the trial without having to stop the trial to write a
whole new protocol. This will dramatically reduce the time it takes to
move from one drug to another in the trial.
Five new investigational agents currently in development by three major
pharmaceutical companies have already been selected for testing as part
of the first phase of the trial, and will be donated by the companies
with each agent representing a different drug class or type of chemical
mechanism for attacking cancer. The first agents expected to be tested
include:
-
ABT-888 (veliparib), a PARP inhibitor being developed by Abbott
Laboratories, Abbott Park, IL
-
AMG 655 (conatumumab), an APO/TRAIL inhibitor and AMG 386,
an angiogenesis inhibitor, both under development at Amgen, Thousand
Oaks, CA
-
CP-751,871 (figitumumab), an IGFR inhibitor and HKI-272
(neratinib), a Pan ErbB inhibitor both under development at
Pfizer, Inc., New York, NY
I-SPY 2 will be coordinated by two principal investigators, Laura
Esserman, M.D., M.B.A., Professor and Director, Carol Franc Buck Breast
Care Center at the University of California, San Francisco (UCSF), and
Donald Berry, Ph.D., Professor and Chair, Department of Biostatistics,
Division Head, Division of Quantitative Sciences at The University of
Texas M.D. Anderson Cancer Center. Clinical operations of the trial will
be managed by Angie DeMichele, M.D., M.S.C.E., Associate Professor of
Medicine and Epidemiology of the Abramson Cancer Center at the
University of Pennsylvania Medical Center. Nola Hylton, Ph.D., Professor
of Radiology and Director of the Breast MRI Research Program at UCSF
developed new tools to use MRI as a quantitative measure of response to
therapy developed in a previous research study, I-SPY 1; these tools
will be an integral part of the I-SPY 2 trial and will help validate
whether MRI tumor volume change, rather than surgery, can be used as a
way of determining patients’ response to treatment.
“I-SPY 2 will provide a path to personalized medicine,” said Dr.
Esserman, a breast cancer surgeon and researcher at UCSF. “The
collaborative power behind this trial is truly transformational for
breast cancer patients and for cancer research as a whole. We have set
up a system where everyone can learn faster and, together, we can
dramatically reduce the amount of time and the cost to bring those drugs
to market that can make a difference in whether women live or die.”
“A considerable advantage for trial participants in I-SPY 2 is that
drugs and drug combinations can be given to more patients in the trial
as soon as they are proven to be clearly beneficial,” added Dr. Berry,
who supervised development of the innovative Bayesian adaptive design
for I-SPY 2. “By the same token, drugs that are ineffective in the trial
can be dropped just as quickly, which increases the safety of the study.”