Daiichi Sankyo initiates DESTINY-Breast 04 trial of[fam-] trastuzumab deruxtecan in patients with HER2 low, unresectable and/or metastatic breast cancer.

- Daiichi Sankyo Company, Limited announced that the first patient has been dosed in DESTINY-Breast04 , a global pivotal phase III study evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), in patients with HER2 low, unresectable and/or metastatic breast cancer previously treated with standard chemotherapy.

Over 40 percent of all breast cancers express low levels of HER2 as a cell surface antigen (IHC 2+/ISH- or IHC 1+), but no anti-HER2 therapies are currently approved for these low expressing tumors. In current clinical practice, these patients are classified and treated according to guidelines for HER2 negative breast cancer and according to the hormone receptor (HR) status. Many patients eventually progress on current treatments to a point where limited options are available. For HER2 negative, HR positive breast cancer, guidelines recommend endocrine therapy plus a cyclin-dependent kinase (CDK) 4/6 inhibitor, and, if tumors become resistant, physician�s choice of single-agent chemotherapies is recommended. For HER2 negative, HR negative breast cancer (�triple negative"), treatment is typically with physician�s choice of single-agent chemotherapies.

�DESTINY-Breast04 has been initiated based on preliminary phase 1 study results to determine whether [fam-] trastuzumab deruxtecan could serve as a targeted therapy option for patients with HER2 low metastatic breast cancer that progresses after standard chemotherapy, regardless of HR status,� said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. �HER2 targeting agents have improved survival rates for HER2 positive breast cancer, but none have been approved in HER2 low expressing tumors. DESTINY-Breast04, our third phase III breast cancer trial with [fam-] trastuzumab deruxtecan, has potential to define a new patient population for HER2 targeted treatment.�

About DESTINY-Breast04 :DESTINY-Breast04 is a randomized, active-controlled, open-label, multicenter, two-arm, global phase III trial designed to compare the safety and efficacy of [fam-] trastuzumab deruxtecan versus investigator�s choice (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel) in patients with HER2 low, unresectable and/or metastatic breast cancer previously treated with one to two prior lines of chemotherapy. Patients will be confirmed as low HER2 expression (defined as IHC 2+/ISH- or IHC 1+) through evaluation at a central laboratory. The primary efficacy endpoint of DESTINY-Breast04 is progression-free survival based on blinded independent central review. Secondary efficacy endpoints include progression-free survival based on investigator assessment, overall survival, objective response rate and duration of response. Safety endpoints include serious adverse events, treatment-emergent adverse events and adverse events of special interest. Health economics and outcomes research endpoints as well as pharmacokinetic and biomarker endpoints will also be measured. .

Breast cancer is the most common cancer and the most common cause of cancer mortality among women worldwide. There were approximately 1.67 million new cases of breast cancer diagnosed in 2012. Appromixately one in five breast cancers (20 percent) are HER2 positive (IHC 3+ or IHC 2+/ISH+). HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis. A number of HER2 targeting therapies are approved to treat HER2 positive metastatic breast cancer and have improved survival rates. The remaining 80 percent of breast cancers are classified as HER2 negative; however, over 40 percent still express some level of HER2 as a cell surface antigen and as measured by immunohistochemistry (IHC). No anti-HER2 agents are indicated for these low expressing tumors, which may be defined as IHC 2+/ISH- or IHC 1+.2.