Quantum Leap Healthcare Collaborative

Press Release

Widely hailed as the future of phase II drug development, the adaptive I-SPY2 platform trial has set a new benchmark for efficiency, through innovation in trial design and clinical operations.

Merck & Co. MK-2206 "Graduates" From I-SPY 2

MK-2206 plus standard neoadjuvant therapy beneficial in all hormone receptor (HR)-negative, all HER2-positive, and HR-negative/HER2-positive tumors

SAN FRANCISCO, CA, 1 June 2015 -- QuantumLeap Healthcare Collaborative today announced top line results for the investigational AKT inhibitor, MK-2206, developed by Merck (known as MSD outside the United States and Canada), in the Phase II I-SPY 2 TRIAL for the neoadjuvant treatment of breast cancer.

The I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) is a randomized Phase II clinical trial for women with newly diagnosed Stage 2 or 3 breast cancer that addresses whether adding biologically targeted investigational drugs to standard chemotherapy in the neoadjuvant (pre-operative) setting is better than standard chemotherapy. The trial enrolls patients who have a high risk of relapse using up-front tumor profiling (including tumor size, hormone receptor status (HR), HER2 status, and the MammaPrint 70-gene signature test).

The primary endpoint is pathological complete response (pCR) in the breast and the lymph nodes at the time of surgery. The goal of the trial is to match investigational regimens with patient subsets on the basis of molecular characteristics (referred to as biomarker signatures) that benefit from the regimen. The I-SPY 2 TRIAL is a collaborative effort among academic investigators from 20 major cancer research centers across the U.S. and Quantum Leap Healthcare Collaborative, the U.S. Food and Drug Administration, and the Foundation for the National Institutes of Health (FNIH) Cancer Biomarkers Consortium. Major supporters include The Safeway Foundation and the Bill Bowes Foundation.

The MK-2206-containing regimen [MK-2206 plus paclitaxel (and trastuzumab, if HER2+) followed by doxorubicin and cyclophosphamide] graduated from the I-SPY 2 TRIAL based on having a high probability of success in a subsequent Phase III trial for 3 biomarker signatures: all hormone receptor (HR)-negative, all HER2-positive, and HR-negative/HER2-positive. There were 94 patients adaptively randomized to MK-2206 in the trial and 59 patients concurrently randomized to control (same therapy without MK-2206).

Full results of the I-SPY 2 TRIAL for MK-2206 will be presented at ASCO in May 2015. “Finding the right, breakthrough scientific approach to help cancer patients achieve better outcomes is at the core of our entire oncology research effort at Merck,” said Dr. Eric Rubin, vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. “We are pleased that MK-2206 has graduated from the I-SPY 2 trial and we are honored to have been involved in this innovative study.”

The lead investigators on the MK-2206 regimen in the I-SPY 2 TRIAL are Debu Tripathy, Chair of Breast Medical Oncology from The University of Texas MD Anderson Cancer Center, and Jo Chien, Assistant Professor from University of California, San Francisco (UCSF). “It is rewarding to see the first proof of concept that blocking AKT, a member of an important growth signaling pathway, can benefit patients,” said Debu Tripathy.

The I-SPY 2 Trial uses adaptive randomization to efficiently identify subtypes of patients—if any—who benefit from each of the many therapies being considered in the trial. The trial’s innovative design was developed by the overall principal investigators for the I-SPY trial, 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, and Donald A. Berry, Ph.D., professor of biostatistics at The University of Texas MD Anderson Cancer Center and founder of Berry Consultants. "We are excited about the very promising results for MK-2206 in I-SPY 2, and we look forward to the possibility of confirming these results in I-SPY 3 as we move forward in our quest to accelerate the development of better treatments for women who stand to benefit from them the most," said Dr. Esserman. “To keep pace with the major advances we are seeing today in biology, our clinical trial designs must be able to adapt and change. I-SPY 2 and 3 are examples of this evolution and these promising results for MK-2206 are exactly what we were hoping to find in our study,” added Dr. Berry.”

About MK-2206

MK-2206, Merck’s investigational, orally available, allosteric small-molecule inhibitor of AKT, is currently being studied for the treatment of breast cancer and other solid tumors. In pre-clinical models, MK-2206 has been shown to bind to and inhibit the activity of AKT in a non-ATP competitive manner, which may result in the inhibition of the PI3K/AKT signaling pathway. MK-2206 can inhibit tumor cell proliferation and induce apoptosis (cell death) in some of those models. For further information about ongoing clinical trials, please visit clinicaltrials.gov.

About QuantumLeap Healthcare Collaborative

QuantumLeap Healthcare Collaborative, a non-profit foundation, was established in 2005 as a collaboration between medical researchers at University of California, San Francisco (UCSF), 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 its companion phase III confirmatory trial, I-SPY 3. For more information, visit: http://www.quantumleaphealth.org.

More About the I-SPY 2 TRIAL

The I-SPY 2 TRIAL involves an adaptive trial design based on Bayesian predictive probability that a biological regimen will be shown to be statistically superior to standard therapy in an equally randomized 300-patient confirmatory trial. Regimens that have a high Bayesian predictive probability of showing superiority in at least one of 10 predefined signatures graduate from the trial. Regimens are dropped for futility if they show a low predictive probability of showing superiority over standard therapy in all 10 signatures. A maximum total of 120 patients can be assigned to each experimental regimen. A regimen can graduate early and at any time after having 60 patients assigned to it.

Media Contact:

Karyn DiGiorgio
Quantum Leap Healthcare Collaborative