DESTINY-Breast11 Neoadjuvant Phase 3 Trial of ENHERTU® Initiated in Patients with High-Risk HER2 Positive Early-Stage Breast Cancer

TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ, USA I November 30, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that the first patient was dosed in the global DESTINY-Breast11 phase 3 trial evaluating the efficacy and safety of ENHERTU® (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), as a neoadjuvant therapy in patients with high-risk HER2 positive early-stage breast cancer.

DESTINY-Breast11 will evaluate ENHERTU as a monotherapy or ENHERTU followed by paclitaxel, trastuzumab and pertuzumab (THP) compared to the standard of care regimen of doxorubicin and cyclophosphamide followed by paclitaxel, trastuzumab and pertuzumab (ddAC-THP) in patients with high-risk (lymph node positive [N1-3] or with a primary tumor stage T3-4), locally advanced or inflammatory, HER2 positive early-stage breast cancer.

Breast cancer is the most common cancer worldwide with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 About 60% of women with breast cancer are diagnosed with early-stage breast cancer.2 The current standard of care in the neoadjuvant setting of HER2 positive early-stage breast cancer consists of a multi-agent regimen of dual HER2 targeted therapy with three different chemotherapy agents.3 While the goal of this regimen is to achieve a pathologic complete response (pCR), or the absence of active cancer cells prior to surgery, it is associated with significant toxicity.3,4 Additionally, some patients will experience disease relapse or progression.3 Replacing the standard of care with ENHERTU or displacing anthracyclines with ENHERTU followed by THP may potentially improve outcomes and could reduce treatment burden and overall toxicity in patients not benefiting from standard of care therapy.

“DESTINY-Breast11 is the first trial to evaluate ENHERTU in the neoadjuvant setting in patients with high-risk HER2 positive early-stage breast cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “The goal of this study is to determine if ENHERTU alone or followed by chemotherapy can potentially replace the current standard of care or displace the use of anthracylines in the neoadjuvant setting.”

About DESTINY-Breast11
DESTINY-Breast11 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of neoadjuvant ENHERTU (5.4 mg/kg) monotherapy or ENHERTU followed by THP as compared to the standard of care regimen ddAC-THP in patients with high-risk (lymph node positive [N1-3] or with a primary tumor stage T3-4), locally advanced or inflammatory HER2 positive early-stage breast cancer.

Patients will be randomized 1:1:1 to receive either eight cycles of ENHERTU as a monotherapy; four cycles of ENHERTU followed by four cycles of THP; or four cycles of ddAC followed by four cycles of THP. The primary endpoint of DESTINY-Breast11 is pCR (absence of invasive disease in the breast and lymph nodes) as assessed by blinded independent central review (BICR). Secondary endpoints include event-free survival, invasive disease-free survival, overall survival, pharmacokinetics, immunogenicity and safety.

DESTINY-Breast11 will enroll approximately 624 patients at multiple sites across Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

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 cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 About 60% of women with breast cancer are diagnosed with early-stage breast cancer.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.5 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.6 Approximately one in five cases of breast cancer are considered HER2 positive.7

The current standard of care in the neoadjuvant setting of HER2 positive early-stage breast cancer consists of a multi-agent regimen of dual HER2 targeted therapy with three different chemotherapy agents.3 While the goal of this regimen is to achieve a pathologic complete response (pCR), or the absence of active cancer cells prior to surgery, it is associated with significant toxicity.3,4 Additionally, some patients will experience disease relapse or progression.3 Replacing the standard of care with ENHERTU or displacing anthracyclines with ENHERTU followed by THP may potentially improve outcomes and could reduce treatment burden and overall toxicity in patients not benefiting from standard of care therapy.

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 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 two or more prior anti-HER2 based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4 mg/kg) is also approved in Israel, Japan, Singapore and U.S. 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. A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen.

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 non-small cell lung cancer (NSCLC), based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.

In September 2021, ENHERTU received its fourth Breakthrough Therapy Designation (BTD) in the U.S for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.

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 Sung H, et al. CA Cancer J Clin. 2021; 10.3322/caac.21660.
2 Cancer.net. Breast Cancer Statistics. Accessed October 2021.
3 Ban M, et al. Br Cancer. 2020; 15:560–568.
4 Spring LM, et al. Clin Cancer Res. 2020 Jun 15;26(12):2838-2848.
5 Iqbal N, et al. Mol Biol Int. 2014;852748.
6 Pillai R, et al. Cancer. 2017;1;123(21):4099-4105.
7 Ahn S, et al. J Pathol Transl Med. 2020; 54(1): 34-44.

SOURCE: Daiichi Sankyo

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