Researchers at Daichi Sankyo initiation the DESTINY-Breast01, a pivotal phase II study evaluating the safety and efficacy of DS-8201, an investigational HER2-targeting antibody-drug conjugate or ADC, in patients with HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to ado-trastuzumab emtansine (T-DM1 | Kadcyla®; Genentech/Roche).
About one in five patients with breast cancer overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.
Depending on several factors, including the biomarker classification, breast cancer is typically treated with various combinations of surgery, radiation, chemotherapy, hormone therapy or targeted therapy.
But many HER2-positive tumors progress to the point where no currently approved HER2-targeting treatments can continue to control the disease. Furthermore, there is no HER2-targeting therapies approved for HER2-weak positive tumors after treatment with trastuzumab, pertuzumab and T-DM1. 
The Pivotal phase II DESTINY-Breast01 study examines the efficacy and safety of DS-8201 in patients with HER2-positive unresectable and/or metastatic breast cancer who are resistant or refractory to ado-trastuzumab emtansine (T-DM1)
DS-8201 is the lead investigational drug being developed by the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are a type of targeted cancer medicine that deliver cytotoxic chemotherapy or payload to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
Using Daiichi Sankyo‘s proprietary ADC technology, DS-8201 is a ‘smart’ chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. The agent is designed to deliver enhanced cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.
“The initiation of this phase II study represents an important next step to rapidly advance the development of DS-8201, as we will obtain a better understanding of how the smart delivery of chemotherapy directly to targeted cancer cells may help patients with HER2-expressing metastatic breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo.
“In addition to this pivotal study, we will continue to evaluate DS-8201 in other HER2-expressing cancers as well as in combination with other therapies where science suggests that it may help improve patient outcomes.”
In an interview for The Onco’Zine Brief, a podcast on PRX, Public Radio Exchange, during the 2017 annual meeting of the American Society of Clinical Oncology, or ASCO, which took place June 2nd to 5th in Chicago, Illinois, Yver, explained the progress Daiichi Sankyo has made in the development of DS-8201, and how this investigational drug has demonstrated a favorable safety profile and promising antitumor activity.
DESTINY-Breast01 is a pivotal phase II, open-label, global, multicenter, two-part study evaluating the safety and efficacy of DS-8201 in patients with HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1. The primary endpoint of the study is objective response rate. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. The first part of the study will include a pharmacokinetic stage and a dose finding stage to identify the recommended dose of DS-8201 to be evaluated in the second part of the study.
The second part of the study will enroll patients into one of two cohorts: patients resistant or refractory to T-DM1 (part 2a) and patients who discontinued treatment with T-DM1 for reasons other than resistant or refractory disease (part 2b). DESTINY-Breast01 is expected to enroll more than 230 patients at up to 90 sites in North America, Europe, Japan and other countries in Asia.
In addition to the DESTINY-Breast01 study, DS-8201 is in phase I development for HER2 low-expressing breast cancer, HER2-positive gastric cancer, and other HER2-expressing solid tumors.
Earlier, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to DS-8201 for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab (Herceptin®; Genentech/Roche) and pertuzumab (Perjeta®; Genentech/Roche) and have disease progression after ado-trastuzumab emtansine, and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1.