TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ, USA I June 14, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced that the first patient was dosed in DESTINY‑Breast09, a global head-to-head phase 3 trial evaluating the safety and efficacy of ENHERTU® (trastuzumab deruxtecan) with or without pertuzumab compared to standard of care (THP: taxane, trastuzumab and pertuzumab) as a potential first-line treatment in patients with HER2 positive metastatic breast cancer. This is the first trial to evaluate ENHERTU in the first-line metastatic setting in patients with HER2 positive breast cancer.
Many patients with HER2 positive metastatic breast cancer have aggressive disease due to progression from an earlier stage, with a significant proportion having their disease relapse after receiving THP or other standard anti-HER2 therapies in an adjuvant setting.1 Research has also shown that patients often progress in less than two years following initial treatment for HER2 positive metastatic breast cancer.1 While there have been substantial advances in the treatment of these patients, there remains an ongoing need to improve outcomes, and as a result more effective HER2 directed treatments and novel combination regimens are needed.1,2
“There have been no significant advances in first-line metastatic breast cancer treatment in nearly a decade, and most patients still progress on the current standard of care THP regimen, highlighting the need for more effective HER2 directed treatments and novel combination regimens,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Based on the encouraging results we are seeing in patients who have received prior treatment for HER2 positive metastatic breast cancer, we have initiated DESTINY-Breast09 to evaluate whether earlier use of ENHERTU alone or as part of a novel combination regimen may help improve outcomes for patients in the first-line metastatic setting as compared to the current standard of care.”
About DESTINY-Breast09
DESTINY-Breast09 is a global head-to-head phase 3 trial evaluating the safety and efficacy of ENHERTU (5.4 mg/kg) with or without pertuzumab compared to standard of care (THP: taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a first-line treatment in patients with HER2 positive metastatic breast cancer.
Patients will be randomized 1:1:1 to receive either ENHERTU as a monotherapy with a pertuzumab‑matching placebo; ENHERTU in combination with pertuzumab; or, current THP standard of care (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab). Randomization will be stratified by prior treatment (de novo versus recurrent with de novo capped at 50%), hormone receptor (HR) status and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is progression-free survival (PFS) as assessed by blinded independent central review. Secondary endpoints include investigator-assessed PFS; overall survival (OS); objective response rate; duration of response; time to second progression or death; health-related quality of life (QoL); time to deterioration of physical and role function, global health status/QoL and pain scores; generation of antibodies against ENHERTU or pertuzumab; immunogenicity; pharmacokinetics; and safety.
DESTINY-Breast09 will enroll approximately 1,134 patients at multiple sites in Africa, Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.
About HER2 Positive Breast Cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.3 More than two million cases of breast cancer are diagnosed each year, resulting in nearly 685,000 deaths globally.3
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. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4 Approximately one in five cases of breast cancer are considered HER2 positive.5
In the first-line HER2 positive metastatic breast cancer setting, approximately 50% of cases are considered de novo, meaning the disease is metastatic from initial diagnosis, while the remaining cases occur due to disease progression from early stage disease.1 While research has shown that patients with recurrent disease have worse clinical outcomes than patients with de novo metastatic disease, patients diagnosed with de novo metastatic disease also often progress in less than two years.1 The current standard of care for patients with first-line metastatic breast cancer is the THP regimen, which was approved nearly a decade ago.1,6 More effective HER2 directed treatments and novel combination regimens are needed for patients with first-line HER2 positive metastatic breast cancer.1,2
About ENHERTU
ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed antibody drug conjugate (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 (5.4 mg/kg) is approved in Canada, EU, Japan, UK and the U.S., 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 in the metastatic setting based on the results from the DESTINY-Breast01 trial.
ENHERTU (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction 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. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
ENHERTU was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in NSCLC, based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial. In May 2020, ENHERTU received Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019, and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.
U.S. Important Safety Information for ENHERTU
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated 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 in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Daiichi Sankyo in Oncology
The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class 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.
References:
1 Tripathy D, et al. The Oncologist. 2020; 25(2):e214-e222.
2 de Melo Gagliato D, et al. Oncotarget. 2016 Sep 27;7(39):64431-64446.
3 Sung H, et al. CA Cancer J Clin. 2021; 10.3322/caac.21660.
4 Iqbal N, et al. Mol Biol Int. 2014;852748.
5 Ahn S, et al. J Pathol Transl Med. 2019; 54(1): 34–44.
6 Blumenthal G, et al. Clinical Cancer Research. 2013;19(18).
SOURCE: Daiichi Sankyo
