SAN FRANCISCO, CA – July 7, 2016 –Two articles published today in the July 7, 2016 issue of the New England Journal of Medicine (NEJM) reinforce the importance of multi-drug standing platform clinical trials, in particular the I-SPY 2 Phase 2 Clinical Trial for Breast Cancer (I-SPY 2), to accelerate identification and development of effective treatments for challenging diseases such as women with primary breast cancer at high risk for early recurrence, including triple negative and HER2-positive breast cancer.In Adaptive Randomization of Veliparib—Carboplatin Treatment in Breast Cancer and Adaptive Randomization Trial of Neratinib in Breast Cancer, the authors provide methodology and statistical evidence clearly indicating the potential for I-SPY 2 to accelerate the process of screening drugs. I-SPY 2 seeks to provide the basis for personalizing treatments with a novel study design. Its goals are to improve the efficiency of clinical trials and to streamline the process of finding genetically targeted treatments for patient subgroups and accelerate the development of these new regimens where they are most urgently needed.

More than 45 investigators, from the nation’s most prestigious and innovative cancer research centers, co-authored the two NEJM articles, with hundreds of staff and investigators involved in I-SPY 2 overall. The Principal Investigators for I-SPY 2 are Laura J. Esserman, M.D., M.B.A., Professor of Surgery and Radiology and Director of the Carol Franc Buck Breast Care Center at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, and Donald A. Berry, Ph.D., Professor in the Department of Biostatistics at The University of Texas MD Anderson Cancer Center, and founder of Berry Consultants. A complete list of the participating centers and investigators is provided in a Supplementary Appendix available at NEJM.org.

Sponsored by QuantumLeap Healthcare Collaborative, and launched through a unique partnership with the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium, I-SPY 2 is an ongoing, multicenter, open-label, adaptive, phase 2 master platform trial that is continuously evaluating new experimental drugs combined with standard neoadjuvant (pre-surgery) therapy for the treatment of breast cancers that have a high risk of recurrence. The primary endpoint is pathological complete response (pCR), which is defined as the absence of residual cancer in the breast or lymph nodes at the time of surgery.

“The goal of I SPY 2 was to develop a replicable platform for finding the right agents and regimens for the right patients and to dramatically accelerate the process for doing so,” said Dr. Esserman, “These early successes should inspire the use of this approach for other cancers and diseases as well.”

I-SPY 2 data presented in the two NEJM articles shows that when added to standard, neoadjuvant chemotherapy, the combination of the molecularly targeted experimental drug veliparib (AbbVie Inc.) plus carboplatin showed sufficient improvement to meet the pre-specified threshold for “graduation” from the trial, signifying a high likelihood for success in a modest, confirmatory phase 3 neoadjuvant trial in the triple negative subset. Likewise, the experimental drug neratinib (Puma Biotechnology) was found to have sufficient improvement in the pCR rate for patients in the HER2-positive/HR-negative subset, that it too was “graduated” from the I-SPY 2 trial.

"We need better designs for clinical trials that will learn more rapidly which patients benefit from which therapies. I-SPY 2 is a foray into this Brave New World,” said Dr. Berry. “Biology is the essential guide, but the bottom line is the patient. In I-SPY 2 we use adaptive randomization to speed learning and to improve treatment for trial participants because they are more likely to receive therapies that are performing well for patients who have their version of the disease.”
“Another important contribution of the I-SPY trial,” Dr. Esserman adds, “is determining which drugs are not successful, and identifying patient subsets for whom ‘graduating’ drugs offer no benefit.”

“Our focus is the future,” Berry adds, “We constantly update what we know about the various therapies in the trial and we continually ask whether any of the therapies is ready for further development in phase 3. I-SPY 2-like trials are being developed in many cancers and for diseases beyond cancer, including Alzheimer’s, pneumonia, and Ebola."

A major achievement in the progression of I-SPY 2 has been significantly reducing the time it takes to move forward from initiation of discussions with drug companies to enrollment of the first patients. I-SPY 2 has compressed this timeline from an average timeframe of 18 - 36 months to five months. The I-SPY 2 study start-up period takes approximately 45-60 days, with more than 50% of the sites opening and enrolling patients, as opposed to the traditional study start-up timing of 10 to 13 months, with less than 25% of the sites opening and enrolling.

“I-SPY’s innovative statistical design, structure and operational processes allow us to bring drugs into the pipeline quickly and evaluate them efficiently for their success in phase 3 registration trials,” says Meredith Buxton, PhD, Executive Director of the I-SPY Program. “I-SPY has pioneered this type of platform trial. Now, with over 6 years experience and 1,000 patients enrolled, we have strong evidence to support the success of this model for testing new drugs.”
To date, I-SPY has screened more than 1800 volunteers (with 1000 randomized). Since its inception in 2010, I-SPY 2 has included 11 investigational drugs from eight pharmaceutical companies, completing the evaluation on 7 drugs, with 5 drugs “graduating” (identified as excellent candidates to move onto a phase 3 trial) and a robust pipeline in development. See the ispytrials.org website for a list of additional publications and presentations, as well as, other I-SPY Program initiatives.

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Links to editorial Articles from New England Journal of Medicine:

• I-SPY 2 -- Toward More Rapid Progress in Breast Cancer
• I-SPY 2 -- A Glimpse of the Future of Phase 2 Drug Development‍
  

About QuantumLeap Healthcare Collaborative

The I-SPY 2 Trial is sponsored by QuantumLeap Healthcare Collaborative, a non-profit foundation that was established in 2005 as a collaboration between medical researchers at University of California at San Francisco, and Silicon Valley entrepreneurs. QuantumLeap’s mission is to accelerate transfer of high-impact research in clinical processes and systems technology into widespread adoption so that patients and physicians can benefit from the research as soon as practicable. QuantumLeap provides operational, financial and regulatory oversight to I-SPY 2 and is also the sponsor of the I-SPY Phase 1 program and I-SPY 3, a companion phase 3 confirmatory trial that is in development. For more information, visit: http://www.quantumleaphealth.org.

Media Contact:

Caren Browning
King + Company, for QuantumLeap Healthcare Collective
(212) 561-7464 – Office
(917) 334-6397 – Cell
Caren.browning@kingcompr.com
EMBARGOED UNTIL JULY 6, 2016 – 6:00 PM ET

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