Tokyo, Munich and Basking Ridge, NJ - Positive topline results from the DESTINY-Breast02 phase 3 trial of ENHERTU (trastuzumab deruxtecan) versus physician's choice of treatment showed the trial met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1). The trial also met the key secondary endpoint of improved overall survival.
ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN). The trial evaluated a similar later-line patient population as the single-arm DESTINY-Breast01 phase 2 trial, which is the basis for initial approvals in advanced HER2 positive metastatic breast cancer. The safety profile of ENHERTU was consistent with previous phase 3 clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) rates and severity were consistent with those observed in other metastatic breast cancer trials of ENHERTU, with a low rate of grade 5 ILD observed as determined by an independent adjudication committee.
'The topline results from DESTINY-Breast02 confirm the robust progression-free survival seen in previous trials of ENHERTU and enrich our clinical understanding of the benefit this therapy may offer patients with HER2 positive metastatic breast cancer,' said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. 'As this is the confirmatory trial for our current breast cancer indication in Europe and several other countries, we look forward to sharing these findings with regulatory authorities to add to the body of data for ENHERTU for the treatment of HER2 positive metastatic breast cancer.' 'The DESTINY-Breast02 trial results in this patient population with advanced disease confirm the efficacy and safety profile seen in DESTINY-Breast01 and are consistent with the results seen across our broader 2 clinical program in HER2 positive metastatic breast cancer,' said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. 'These data further strengthen our confidence in ENHERTU and reinforce its potential to transform patient outcomes across multiple treatment settings.' The data will be presented at an upcoming medical meeting.
About DESTINY-Breast02
DESTINY-Breast02 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus physician's choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1. Patients were randomized 2:1 to receive either ENHERTU or physician's choice of treatment. The primary endpoint of DESTINY-Breast02 is PFS based on blinded independent central review (BICR). The key secondary endpoint is overall survival. Other secondary endpoints include objective response rate based on BICR and investigator assessment, duration of response based on BICR, PFS based on investigator assessment and safety.
About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.1 Approximately one in five patients with breast cancer are considered HER2 positive.2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca's ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior antiHER2-based regimen either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on results from the DESTINY-Breast03 trial. ENHERTU (5.4 mg/kg) also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results of the DESTINY-Lung02 trial.
ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial. ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our worldclass science and technology for our purpose 'to contribute to the enrichment of quality of life around the world.' In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an 'Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.' For more information, please visit www.daiichisankyo.com.
Contact:
Japan
Masashi Kawase
Daiichi Sankyo Co., Ltd.
E: kawase.masashi.a2@daiichisankyo.co.jp
T: +81 3 6225 1126
DAIICHI SANKYO CO., LTD. 
