Quantum Leap Healthcare Collaborative Announces the Selection of Sanofi’s SAR439859 as the oral SERD Backbone Agent in the Endocrine Optimization Pilot Study of the I-SPY 2 TRIAL for Clinically High Risk, Molecularly Low Risk Stage 2/3 Breast Cancer

Quantum Leap Healthcare Collaborative™ (Quantum Leap) announced today an evaluation of SAR439859, an oral estrogen receptor degrader (SERD) in a new I-SPY 2 study arm targeting patients with newly diagnosed hormone receptor-positive (HR+) clinical stage 2/3 invasive breast cancer.

This study arm, known as the I-SPY-2 Endocrine Optimization Pilot Protocol (EOP), is focused on patients with molecularly low risk (MammaPrint low risk signature), clinically high risk, hormone receptor positive (HR+), and HER2-negative breast cancer.  These patients historically have been excluded from the I-SPY2 trial due to the predicted lack of chemotherapy benefit.  However, these patients often have late risk of recurrence (after 5 years), and thus also need novel strategies that are more tolerable and more effective than the current standard. The EOP is a sub-study within the main I-SPY-2 clinical trial utilizing an endocrine therapy backbone for patients whose tumors are predicted to be sensitive to endocrine therapy but for whom chemotherapy provides little or no benefit. 

The selective estrogen receptor degrader (SERD) class of compounds have demonstrated benefit in HR+ HER2-negative metastatic breast cancer, including tumors with estrogen receptor activating mutations.  They appear to be very well tolerated. Next-generation orally-bioavailable SERDs with improved pharmacokinetic properties are promising potential therapies for HR+ breast cancer.  The EOP study will use an oral SERD as the endocrine therapy backbone. Sanofi’s SAR439859 has been selected as the oral SERD for this study. SAR439859 is a potent, orally bioavailable, and selective estrogen receptor (ER) inhibitor that belongs to the selective estrogen receptor degrader (SERD) class of compounds. SAR439859 antagonizes the binding of estradiol to ER but also promotes the transition of ER to an inactive conformation that results in up to 98% receptor degradation at nanomolar concentrations in cellular assays. These dual properties of SAR439859 we hope will translate to a deeper inhibition of ER pathways and a more effective antiproliferative activity in ER-dependent breast cancer cell lines driven by mutant or wild-type ER compared to other ER inhibitors. SAR439859 is an investigational compound and its safety and efficacy have not been evaluated by any regulatory authority.

In EOP, Sanofi’s oral SERD will be evaluated alone and in combination with up to three other investigational agents for a total of up to four study arms.  The combination partner agents will be selected based on complementary biology utilizing orthogonal mechanisms of action.  I-SPY 2 principal investigator, Dr. Laura Esserman of the University of California San Francisco, stated,

“The whole I-SPY team is excited to have Sanofi as a partner in this endeavor. This is an important advance for patients with hormone positive high clinical risk breast cancer profiles who are not responsive to chemotherapy and for whom standard hormonal therapies may not be sufficient.  As well, we need endocrine therapies that are easier for women to tolerate. We are committed to finding more effective, less toxic treatments and this partnership with Sanofi will help us to achieve this goal. Using the I-SPY model we can accelerate the development of new cancer treatments and target new and innovative treatments to the patients who will benefit most.”

Sanofi will supply SAR439859 and provide financial support for this study.  Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.  

About Quantum Leap Healthcare Collaborative
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. Our mission is to integrate care and research, and to foster high-impact trials with embedded clinical processes and systems technology and improved data management, greater access to clinical trial matching, and greater benefit to patients, providers,  and researchers. Our goal is to improve and save lives. Quantum Leap provides operational, financial, and regulatory oversight to I-SPY. For more information, visit https://www.quantumleaphealth.org/. 

About the I-SPY TRIALs
The I-SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis) was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 16 major U.S. cancer research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org.