Business Wire

Trastuzumab Deruxtecan Recommended for Approval in the EU by CHMP for Patients with HER2 Positive Metastatic Breast Cancer Treated with a Prior Anti-HER2-Based Regimen

Share

Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) trastuzumab deruxtecan has been recommended for approval in the European Union (EU) as a monotherapy 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.

Trastuzumab deruxtecan is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast03 phase 3 trial, which were published in TheNew England Journal of Medicine. In the DESTINY-Breast03 trial, trastuzumab deruxtecan reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) for patients treated with trastuzumab deruxtecan was not reached (95% CI: 18.5-NE) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2) as assessed by blinded independent central review (BICR).

The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU.

In Europe, more than 530,000 cases of breast cancer are diagnosed annually.1 Approximately one in five cases of breast cancer are considered HER2 positive.2 Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4 More treatment options are needed to further delay progression and extend survival.3,5,6

“Today’s CHMP opinion provides further validation of the significance of the DESTINY-Breast03 trial results, which for the first time showed superiority of trastuzumab deruxtecan in prolonging progression-free survival in patients previously treated for HER2 positive metastatic breast cancer as compared to another HER2 directed ADC,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “This positive CHMP opinion is an important step forward in bringing this potentially practice-changing medicine to patients in Europe to use earlier in the treatment of HER2 positive metastatic breast cancer and builds on the recent approval of trastuzumab deruxtecan in the U.S.”

“This recommendation reflects the transformative progression-free survival benefit seen in the DESTINY-Breast03 trial compared to T-DM1, supporting trastuzumab deruxtecan as a potential new standard of care and setting a new benchmark in the treatment of HER2 positive metastatic breast cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “If approved by the European Commission, patients in Europe may be able to benefit from this important medicine earlier in the treatment of their disease, improving their chance for better outcomes.”

Additional results from the DESTINY-Breast03 phase 3 trial showed that in the secondary endpoint analysis of PFS assessed by investigators, patients treated with trastuzumab deruxtecan experienced an improvement in PFS of 25.1 months (95% CI: 22.1-NE) compared to 7.2 months (95% CI: 6.8-8.3) for T-DM1 (HR=0.26; 95% CI: 0.20-0.35). There was a strong trend towards improved overall survival (OS) with trastuzumab deruxtecan (HR=0.56; 95% CI: 0.36-0.86; p=0.007172), however this analysis is not yet mature and is not statistically significant. Nearly all patients treated with trastuzumab deruxtecan were alive at one year (94.1%; 95% CI: 90.3-96.4) compared to 85.9% of patients treated with T-DM1 (95% CI: 80.9-89.7). Confirmed objective response rate (ORR) was more than doubled in the trastuzumab deruxtecan arm versus the T-DM1 arm (79.7% [n=208; 95% CI: 74.3-84.4] versus 34.2% [n=90; 95% CI: 28.5-40.3]).

The safety profile of the most common adverse events with trastuzumab deruxtecan in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. The most common grade 3 or higher drug-related treatment emergent adverse events in the trastuzumab deruxtecan arm were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%), nausea (6.6%), anemia (5.8%), fatigue (5.1%), vomiting (1.6%), increased alanine aminotransferase (1.6%), decreased appetite (1.2%), increased aspartate aminotransferase (0.8%), diarrhea (0.4%) and alopecia (0.4%). Overall, 10.5% of patients had interstitial lung disease (ILD) or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events (9.7%) were low grade (grade 1 (2.7%) or grade 2 (7.0%)) with two grade 3 (0.8%) events reported. No grade 4 or grade 5 ILD or pneumonitis events occurred.

About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary endpoints include OS, ORR, duration of response, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Results from DESTINY-Breast03 have been published in TheNew England Journal of Medicine. 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.7 More than two million cases of breast cancer were diagnosed in 2020, with nearly 685,000 deaths globally.7 In Europe, more than 530,000 cases of breast cancer are diagnosed annually.1 Approximately one in five cases of 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.8 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.9

Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4 More treatment options are needed to further delay progression and extend survival.3,5,6

About Trastuzumab Deruxtecan
Trastuzumab deruxtecan is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) is approved in Canada, Israel and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a prior anti-HER2-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. Trastuzumab deruxtecan is also approved in approximately 40 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.

Trastuzumab deruxtecan (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.

About the Trastuzumab Deruxtecan Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for trastuzumab deruxtecan are currently under review in China, Europe, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Trastuzumab deruxtecan is under review in Europe for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer must additionally have received or be ineligible for endocrine therapy.

Trastuzumab deruxtecan also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 trial, and in Europe 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 based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Trastuzumab deruxtecan recently was granted Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy 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. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan 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 trastuzumab deruxtecan and datopotamab deruxtecan.

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 Globocan 2020. Europe Fact Sheets. Last accessed: June 2022.
2 Ahn S, et al. J Pathol Transl Med. 2020;54(1):34-44.
3 Barok M, et al. Breast Cancer Res. 2014;16(2):209.
4 Nader-Marta G, et al. How we treat patients with metastatic HER2-positive breast cancer. ESMO Open. 2022;7:1.
5 Mounsey L, et al. Clin Breast Cancer. 2018;18(1):29-37.
6 Martínez-Sáez O, Prat A.JCO Oncol Pract. 2021;10.1200/OP.21.00172.
7 Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.
8 Iqbal N, et al. Mol Biol Int. 2014;852748.
9 Pillai R, et al. Cancer. 2017;1;123(21):4099-4105.

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

Media:
Global:
Victoria Amari
Daiichi Sankyo, Inc.
vamari@dsi.com
+1 908 900 3010 (mobile)

EU:
Simone Jendsch-Dowé
Daiichi Sankyo Europe GmbH
simone.dowe@daiichi-sankyo.com
+49 (89) 7808437 (office)
+49 176 11780822 (mobile)

Japan:
Masashi Kawase
Daiichi Sankyo Co., Ltd.
kawase.masashi.a2@daiichisankyo.co.jp
+81 3 6225 1126 (office)

Investor Relations:
DaiichiSankyoIR@daiichisankyo.co.jp

About Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

H.I.G. Capital Announces the Sale of DGS S.p.A.11.6.2024 12:00:00 CEST | Press release

H.I.G. Capital (“H.I.G.”), a leading global alternative investment firm with $62 billion of capital under management, is pleased to announce that an affiliate has signed a definitive agreement to sell its portfolio company, DGS S.p.A. (“DGS” or the “Group”), a leading firm in the Italian Information Technology market, to DGS Co-Founders and management team in partnership with ICG, a global alternative asset manager. Since its inception in 1997, DGShas supported blue-chip customers in the design, integration, and maintenance of complex IT systems, with a specialization in digital transformation and cybersecurity services. The Group currently has over 1,900 employees, revenues of approximately €300 million, and maintains a group of highly loyal clientele. During H.I.G.’s ownership, DGS has tripled in size and consolidated its position as a leading Italian firm in cybersecurity services and digital transformation. DGS offers its clients sophisticated and proprietary digital transformation

Evertas Names Nick Selby Head of European Underwriting11.6.2024 12:00:00 CEST | Press release

Evertas, the world’s first crypto insurance company, has named Nick Selby as its new Head of European Underwriting. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240611141887/en/ Nick Selby, Executive Vice President and Head of European Underwriting at Evertas (Photo: Business Wire) Selby, an accomplished information and physical security professional, brings two decades of expertise in public and private sector information security, physical security, and complex incident handling, as well as seven years of experience leading teams securing billions of dollars in cryptoassets. Previously, his roles included VP of the Software Assurance Practice at Trail of Bits, Chief Security Officer at Paxos Trust Company, and Director of Cyber Intelligence and Investigations at the NYPD Intelligence Bureau. “Nick is an extremely valuable addition to our European team,” said Evertas CEO and Co-Founder J. Gdanski. “His public and private

Owlet utvider globalt fotavtrykk med lanseringen av medisinsk-sertifisert Dream Sock™ i Storbritannia og over hele Europa11.6.2024 11:00:00 CEST | Pressemelding

Owlet, Inc. («Owlet» or the «Company») (NYSE:OWLT), pioneren innen smart spedbarnsovervåking, kunngjør i dag den britiske og europeiske lanseringen av Dream Sock. Dette er en smart babymonitor med levende helseavlesninger og varsler for friske spedbarn mellom 0-18 måneder og 2,5-13,6 kg. Dette innovative medisinske utstyret gir foreldre helse og viktig informasjon i sanntid, noe som gir uovertruffen trygghet. Denne pressemeldingen inneholder multimedia. Se hele pressemeldingen her: https://www.businesswire.com/news/home/20240611820341/no/ (Photo: Business Wire) «Vi er svært stolte over å lansere Dream Sock til omsorgspersoner over hele Storbritannia og Europa og gi millioner av foreldre mer trygghet mens babyen sover,» sa Kurt Workman, Owlets administrerende direktør og medgründer. «Dream Sock er nå et globalt produkt som er anerkjent som medisinsk nøyaktig og trygt, etter å ha gjennomgått regulatoriske autorisasjoner og sertifiseringer innenfor flere geografier. I dag er misjonen vår

V-Nova Surpasses 1000 Patent Milestone in Media Technology Innovation11.6.2024 10:00:00 CEST | Press release

V-Nova, a leading provider of data compression solutions, video compression technology, XR technology, AI acceleration and parallel processing for a multitude of industries including media and entertainment, today announced its milestone achievement of 1000 active technology patents. This accomplishment underscores V-Nova’s dedication to research and development and its commitment to protecting its intellectual property globally. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240611724561/en/ V-Nova’s patent portfolio spans more than 50 different jurisdictions. Including over 400 patents in Europe, over 200 in the Americas, over 100 in the United States specifically, and over 200 in Asia. V-Nova forged new directions in data processing to enhance digital experiences, maximize efficiency, reduce costs, and increase sustainability. The company leads the way with key international data compression standards for the video indust

Alipay+ Reveals Top Scorer Trophy Design for UEFA EURO 2024™11.6.2024 09:24:00 CEST | Press release

Alipay+, a suite of cross-border mobile payment and digitalization technology solutions operated by Ant International and an Official Partner of UEFA EURO 2024™, today revealed the trophy that will be awarded to the most prolific marksman at the UEFA EURO 2024™ finale on July 14 in Berlin, Germany. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240610328619/en/ The UEFA Top Scorer Trophy presented by Alipay+ is unveiled for UEFA EURO 2024™ (Photo: Business Wire) Sculpted in the shape of the Chinese character “支” (pronounced zhi, and meaning payment as well as support), the trophy reflects Alipay+’s dedication to supporting consumers to enjoy seamless payment and a broad choice of deals using their preferred payment methods while traveling abroad. The character also resembles the fleeting moment of a barefooted striker poised to shoot, evoking the original beauty and power of football – a game that united people across the wo

World GlobeA line styled icon from Orion Icon Library.HiddenA line styled icon from Orion Icon Library.Eye