• Accelerated Approval of Daiichi Sankyo and AstraZeneca’s ENHERTU® (fam-trastuzumab deruxtecan-nxki) based on the pivotal DESTINY-Breast01 trial that showed clinically meaningful and durable responses

TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ, USA I December 20, 2019 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced that the U.S. Food and Drug Administration (FDA) has approved ENHERTU® (fam-trastuzumab deruxtecan-nxki), a HER2 directed antibody drug conjugate (ADC), 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.

“Once patients with HER2 positive metastatic breast cancer progress following at least two HER2 targeted regimens in the metastatic setting, there are limited treatment options,” said Shanu Modi, MD, Breast Medical Oncologist, Memorial Sloan Kettering Cancer Center. “ENHERTU has the potential to become a new standard of care.”

The FDA approval is based on the results of the single-arm, pivotal phase 2 DESTINY-Breast01 trial of ENHERTU (5.4 mg/kg) monotherapy in 184 female patients with HER2 positive metastatic breast cancer. Trial results showed a confirmed objective response rate (ORR) of 60.3% (n=111; 95% CI: 52.9-67.4), including a 4.3% complete response rate (n=8) and a 56.0% partial response rate (n=103).1 A median duration of response of 14.8 months (95% CI: 13.8-16.9) was demonstrated as of August 1, 2019. In addition, a median progression free survival of 16.4 months (95% CI: 12.7-Not Estimable), based on a median follow-up of 11.1 months, was recently reported at the San Antonio Breast Cancer Symposium (SABCS) and published online in The New England Journal of Medicine.2

ENHERTU is approved with a Boxed WARNING for Interstitial Lung Disease (ILD)/pneumonitis and Embryo-Fetal Toxicity. The safety of ENHERTU has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2 positive breast cancer who received at least one dose of ENHERTU (5.4 mg/kg) in the DESTINY-Breast01 trial and a phase 1 trial. ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in six patients (2.6%) – two deaths already reported from the phase 1 trial and four deaths already reported in the phase 2 DESTINY-Breast01 trial. Patients and physicians should be aware of ILD/pneumonitis and patients should be actively monitored for potential signs and symptoms. If ILD/pneumonitis is identified, it should be managed as per the FDA approved Prescribing Information. Management may require dose modification or treatment discontinuation and steroid treatment. ENHERTU can cause fetal harm when administered to a pregnant woman. The most common adverse reactions (frequency ≥20%) were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough and thrombocytopenia.

Patients enrolled in DESTINY-Breast01 received a median of five prior regimens (range: 2 -17) in the locally advanced/metastatic setting. All patients received prior trastuzumab, ado-trastuzumab emtansine, and 66% had prior pertuzumab.

“The approval of ENHERTU underscores that this specifically engineered HER2 directed antibody drug conjugate is delivering on its intent to establish an important new treatment for patients with HER2 positive metastatic breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology R&D, Daiichi Sankyo. “Since the beginning of our clinical trial program four years ago, we have focused on the opportunity to transform the treatment landscape for patients with HER2 positive metastatic breast cancer, and we are extremely proud of how quickly we delivered ENHERTU to patients in the U.S., as ENHERTU represents one of the fastest developed biologics in oncology.”

“ENHERTU has shown impressive results in women with HER2 positive metastatic breast cancer, with the majority of women benefiting from treatment and the median duration of response exceeding 14 months,” said José Baselga, MD, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “With this first approval, we are proud to bring ENHERTU to patients with high unmet need and we look forward to further exploring its potential in additional settings.”

ENHERTU will be available by prescription in the U.S. within the coming weeks. Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the U.S. who are prescribed ENHERTU can access the medication and receive necessary financial support. Provider and patient support, reimbursement and distribution for ENHERTU in the U.S. will be accessible by visiting www.ENHERTU4U.com or calling 1-833-ENHERTU (1-833-364-3788).

Please visit www.ENHERTU.com for full Prescribing Information, including Boxed WARNING, and Medication Guide.


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.

About HER2 Positive Breast Cancer

Approximately one in five breast cancers are HER2 positive.3,4 Despite recent improvements and approvals of new medicines, there remain significant clinical needs for patients with HER2 positive metastatic breast cancer.5,6 This disease remains incurable with patients eventually progressing after available treatment.5,6

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poor prognosis in patients with breast cancer.[7] To be considered HER2 positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.7 A finding of IHC 3+ and/or FISH amplification is considered positive.7

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal phase 2, single-arm, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of ENHERTU in 184 female patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with ado-trastuzumab emtansine (T-DM1). The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include pharmacokinetics, duration of response, disease control rate, clinical benefit rate, progression-free survival, overall survival and safety.

About the Clinical Development Program

A comprehensive development program for fam-trastuzumab deruxtecan-nxki is underway globally with five pivotal trials in HER2 expressing metastatic breast and gastric cancer, including a trial in patients with metastatic breast cancer and low levels of HER2 expression (HER2 low). Phase 2 trials are underway for HER2 expressing advanced colorectal cancer as well as metastatic non-squamous HER2 overexpressing or HER2 mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

A regulatory submission also has been made to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of HER2 positive metastatic breast cancer, and it has previously received SAKIGAKE designation for the treatment of advanced HER2 positive gastric or gastroesophageal junction cancer by Japan’s MHLW.


ENHERTU (fam-trastuzumab deruxtecan-nxki), formerly known as DS-8201, is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced program in AstraZeneca’s ADC Scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is comprised of a HER2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker.

ENHERTU received Priority Review, Breakthrough Therapy Designation, and Fast Track Designation from the FDA for the treatment of select patients with HER2 positive metastatic breast cancer.

About the Collaboration between Daiichi Sankyo and AstraZeneca

In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize fam-trastuzumab deruxtecan-nxki as a potential new medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for the manufacturing and supply.

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com.

Dr. Shanu Modi has received compensation from Daiichi Sankyo for advisory services.


1   ENHERTU Prescribing Information.
2   Modi, S., et. al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. NEJM. December 11, 2019. DOI:10.1056/NEJMoa1914510.
3   Tandon A, et al. HER-2/neu Oncogene Protein and Prognosis in Breast Cancer. J Clin Oncol. 1989;7(8):1120-8.
4   Sledge G, et al. Past, Present, and Future Challenges in Breast Cancer Treatment. J Clin Oncol. 2014;32(19):1979-1986.
5   de Melo Gagliato D, et al. Mechanisms of Resistance and Sensitivity to Anti-HER2 Therapies in HER2+ Breast Cancer. Oncotarget. 2016;7(39):64431-46.
6   National Comprehensive Cancer Network (NCCN). NCCN Guidelines. Breast Cancer. Available at https://nccn.org. Accessed August 2019.
7   American Cancer Society. Breast Cancer HER2 Status. Available at https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed August 2019.

SOURCE: Daiichi Sankyo