SAN FRANCISCO, July 7, 2020 -- Quantum Leap Healthcare Collaborative™ (Quantum Leap) announced today the initiation of an investigational treatment arm with Byondis' [vic-]trastuzumab duocarmazine (SYD985) in the ongoing I-SPY 2 TRIAL™ for neoadjuvant treatment of locally advanced breast cancer. This treatment arm will focus on treatment for HER2 low early-stage breast cancer.

This study arm will evaluate if SYD985 will limit tumor growth in a population of patients whose tumors are not normally treated with HER2-targeted therapies. Specifically, these tumors have low expression of HER2, and require better HER2-targeted drugs in order to be as effectively treated as HER2+ patients.

SYD985 is being developed for the treatment of HER2 expressing or HER2 mutant  tumors. In nonclinical and clinical studies, SYD985 has demonstrated  potent antitumor activity. Based on the preliminary clinical observations in a Phase 1 study, SYD985 demonstrated antitumor activity in HER2-expressing cancers including breast cancer. Researchers and clinicians believe SYD985 inhibits tumor growth for the following reasons: SYD985 is a next generation ADC, comprised of the mAb (monoclonal antibody) trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD895 binds to HER2 on the surface of the cancer cell and is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in death of dividing and non-dividing tumor cells. An earlier phase I study (SYD985.001) in patients with histologically-confirmed, locally advanced or metastatic tumors, concluded that SYD985 is effective in patients with high HER2 levels in their tumor, as well as in a subset of patients with lower levels of expression of the HER2 protein (HER2- low).

The SYD985 arm of the I-SPY 2 clinical trial will be open for randomization to the HER2-low subset of the HER2- I-SPY 2 population, further defined as HER2-low by HER2 immuno histo-chemical staining (i.e. IHC 1+ and 2+) and in-situ hybridization. Tumors will be further characterized by genetic testing employing MammaPrint (MP1 or MP2) and by hormone receptor status (HR+ or HR-). Within the HER2 negative population, patients will be excluded for HER2 IHC 0 and ISH negative.

"This I-SPY 2 TRIAL arm is designed to test a less toxic and a potentially highly effective approach where we need better options for patients." stated Dr. Laura Esserman, Lead PI for the  I SPY 2 TRIALs.  "Low levels of HER2 protein expression are not sufficient to generate a response to traditional HER 2 treatment currently on the market. This particular agent works differently and is a promising way to deliver a targeted toxin. We need to continue to push to find better therapies. The I-SPY investigators are excited to partner with Byondis to test this agent in I-SPY 2."

The I-SPY 2 TRIAL, sponsored by Quantum Leap, is a standing phase 2 randomized, controlled, multicenter study with an innovative Bayesian adaptive design aimed to rapidly screen and identify promising new treatments in specific subgroups of women with newly-diagnosed, high-risk (high likelihood of recurrence), locally-advanced breast cancer (Stage II/III).

Byondis will supply the investigational drug and provide financial and regulatory support.  Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.  

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.

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/.

For more information on Byondis: www.byondis.com

‍