The I-SPY Trial: An Interesting Model that Perhaps NIH & FDA Should Consider for Classes of COVID-19 Studies?

The I-SPY Trial An Interesting Model that Perhaps NIH & FDA Should Consider for Classes of COVID-19 Studies

The I-SPY TRIAL (Investigation of Series studies to Predict Your Therapeutic Response with Imaging and molecular analysis) was set up and sponsored by Quantum Leap Healthcare Collaborative to rapidly screen promising experimental treatments while helping to identify those most effective in particular subgroups based on molecular characteristics (biomarker signatures). A unique collaborative by an open, engaging consortium, including the U.S. Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 16 major U.S. cancer research centers. With over a thousand clinical trials now up and running in response to COVID-19, does it make sense to leverage some of the learnings from I-SPY in the context of COVID-19 investigations?

Members of the TrialSite Network requested more information, so here it goes.

Who is the sponsor, Quantum Leap?

Quantum Leap Healthcare Collaborative is a 501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs with a mission to integrate care and research, this includes supporting and promoting high-impact trials with embedded clinical processes and systems technology and improved data management, greater access to trial matching, and greater benefit to patients, providers and researchers.  Quantum Leap seeks to improve and save lives by providing the operational, financial and regulatory oversight to the I-SPY initiative.

Who are its founders?

The organizational founders include an internationally recognized breast surgeon and breast oncology specialist, Dr. Laura Esserman, Professor of Surgery and Radiology at the University of San Francisco, Director of UCSF Carol Franc Buck Breast Care Center. She led the creation of the Athena Breast Health Network and the Women Informed to Screen Depending on their Measures of risk (WISDOM) Study, and is the Principal Investigator of the I-SPY Trial program. Another co-founder, Dr. Jeffrey Pfeffer, is the Thomas D. Dee II Professor of Organizational Behavior at the Graduate School of Business, Stanford University where he has educated there since 1979. He is the co-author of 15 books including the “Dying for a Paycheck: How Modern Management Harms Employee Health and Company Performance—and What We can Do About it.”

Who are I-SPY Strategy Partners?

Strategic partners include sponsors such as AbbVie Biotherapeutics, Amgen, Genentech/Roche, Medication (Pfizer), Merck, Plexxikon and Synta. A number of important donors can be viewed here

Are they Adaptive Trials?


What is the I-SPY Platform?

Now on the I-SPY 2 platform,  an adaptive clinical trial of multiple Phase 2 treatment regimens combined with standard chemotherapy. I-SPY 2 linked 19 academic cancer centers, two community centers, the FD, the NCI, pharma and biotech sponsors, patient advocates and philanthropic partners including those influential from the Capital of Technology in Silicon Valley.

The I-SPY 2 was designed to explore the hypothesis that various combinations of cancer therapies have different degree of success for different patients. Conventional clinical trials that investigate post-surgical tumor response necessitate a different study with lengthy intervals and sizeable populations to assess each combination.  I-SPY 2 is different in that it is organized around a far more agile, nimble and continuous process. With its organization, supporting technology and design, sponsors can efficiently evaluate multiple therapy regimes by relying on the predictors developed in I SPY 1 that can expeditiously determine whether patients with a particular genetic signature will respond favorably to a treatment.

What is the difference between I-SPY1 and I-SPY 2?

I-SPY 1 was the predecessor trial involving 10 cancer centers and the National Cancer Institute and involved a collaboration to identify response indicators that would best predict survival for women with high-risk breast cancer. See the link for more on the I-SPY trials

What does Adaptive Trial mean here?

Well, I-SPY 2 is adaptive in that the investigators actually learn as they go and hence don’t simply continue to treat patients with a drug that doesn’t work well or is ineffective.

How are patients organized, categorized?

Patients are categorized based on tissue and imaging markers collected early and iteratively (e.g. biomarker could change over time) throughout the study. Hence, earlier insights can influence later on treatment for patients.

What happens to treatments that show results within I-SPY 2? Others?

These treatments can be used in a confirmatory clinical trial, while those treatments that don’t impress can be sidelined or shelved.

Can confirmatory Trials support a path to FDA approval?


Can I-SPY 2 investigate simultaneous candidates from multiple industry participants?

Yes. In fact, this model enables the sponsors to quickly eliminate drugs that don’t perform while progressing those that do. By basing the effort on a single standard arm for comparison of all candidates the trial saves enormous costs as compared to traditional Phase 3 clinical trial. Moreover, the data is shared across participants essentially socializing the effort.

Are I-SPY 2 trial success point the result of a trial design innovation?

No. This is the result, as described in the organization’s website is the result of “pain-staking deconstruction and re-engineering of the entire clinical trial enterprise, from protocol development through registration.

Call to Action: Follow the link to the website to learn more.


This site uses Akismet to reduce spam. Learn how your comment data is processed.