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
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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220624005462/en/
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
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
LumiThera Receives Notice of Award for National Eye Institute Grant to Support a 3 rd Year Extension to LIGHTSITE III, the U.S. Multi-Center Clinical Trial for Treating Dry Age-Related Macular Degeneration27.9.2023 17:28:00 CEST | Press release
LumiThera Inc., a medical device company commercializing a photobiomodulation (PBM) treatment for ocular disorders and disease, today announced it is a recipient of a small business innovative research (SBIR) phase II grant from the National Institute of Health (NIH) and the division of the National Eye Institute (NEI) of up to $2.3M in funding over two years. The NIH/NEI grant supports an open-label human clinical trial in U.S. intermediate dry age-related macular degeneration (dry AMD) subjects that participated in the pivotal LIGHTSITE III trial. LIGHTSITE IIIB will treat patients for 4 rounds of treatment over fourteen months. Sham patients in the previous study will be able to cross over and begin PBM treatment. The LIGHTSITE IIIB extension trial follows the successfully completed LIGHTSITE III trial, which showed a sustained, mean increase in best corrected vision acuity (BCVA) letter score of >5.0 letters from baseline at the 13- and 24-month timepoints (p < 0.0001) using the Co
XPENG Shipped 750 Vehicles to Israel, Coming Closer to G9 and P7's Launch in October27.9.2023 16:02:00 CEST | Press release
XPENG (NYSE: XPEV and HKEX: 9868), a leading smart electric vehicle company, today announced that it has shipped 750 vehicles for the Israeli market, marking this the largest single batch of export this year. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230927239985/en/ Hey XPENG, navigate to Israel! (Photo: Business Wire) The batch left the Guangzhou Port after the conclusion of a ceremony that included local customs officials and port representatives. “We're very grateful for the support of our partners and the local customs officials as we take a significant step toward launching in Israel," said Eric Xu, VP of International Markets, XPENG. "With the help of our local partner, Freesbe, the launch of our smart EVs is just around the corner—and we can't wait." The two models expected to be available in Israel, XPENG P7 and XPENG G9, have also been adapted to meet the preferences of local drivers. Together with Freesbe, wi
SoftServe Debuts Sage, the AI Pathfinder, at Money20/2027.9.2023 15:03:00 CEST | Press release
SoftServe, a premier IT consulting and digital services provider, will debut Sage, the AI Pathfinder, a financial intelligence consultant powered by Generative AI using NVIDIA Avatar Cloud Engine (ACE), at Money20/20 USA. Attendees can interact with the immersive experience offering financial decisioning and education at booth #13117 starting Oct. 22. Sage, the AI Pathfinder, is enhanced with a customized ChatGPT module combined with visual avatars and dynamic content. It features real-time information processing for interactive decision-making to offer personalized financial recommendations. Financial wellness is a struggle for 58% of Americans living paycheck to paycheck. Only 51% have more emergency savings than credit card debt. “A lack of financial literacy is a big part of this problematic equation,” said Filippa Noghani, AVP of Marketing at SoftServe and NYC Fintech Women Board Member. “Generative AI technologies create promising educational opportunities, especially for millenn
PPG’s COLORFUL COMMUNITIES program marks 500th project with makeover at Carnegie Science Center in Pittsburgh27.9.2023 15:00:00 CEST | Press release
PPG (NYSE:PPG) today announced the completion of its 500th COLORFUL COMMUNITIES® project – a colorful and transformational makeover at Carnegie Science Center in Pittsburgh. More than 80 volunteers marked the milestone by creating science-themed murals and applying fresh paint and color in learning spaces around the center. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230927335327/en/ PPG volunteers completed the 500th COLORFUL COMMUNITIES® project at the Carnegie Science Center in Pittsburgh, kicking off a month-long, worldwide celebration. (Photo: Business Wire) Completion of the 500th Colorful Communities project kicks off a month-long, worldwide celebration of the volunteers, community partners and individuals who have helped to bring color and brightness to PPG communities. From China to the Netherlands, additional projects are planned across the world to mark the milestone. “When we launched the Colorful Communities
Syntropy Announces Collaboration with Evidium to Advance Data-Centric Healthcare27.9.2023 15:00:00 CEST | Press release
Today, Syntropy, a partnership between Merck and Palantir Technologies Inc., announced a collaboration with Evidium, a developer of a healthcare platform that enables AI use in a responsible, reliable, and referenceable manner. The organizations will make end-to-end medical knowledge more computational and improve data quality for clinical research and practice. The coalition will be facilitated through Syntropy’s secure data collaboration platform. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230927301328/en/ Evidium’s Referenced AI platform will play a key role in transforming narrative-form information into AI-ready knowledge at the elemental level. This will allow clinical data to be disseminated and utilized with unprecedented scale and precision. Syntropy’s secure, collaborative ecosystem will enable researchers to review high-quality data, share insights, and apply their findings to clinical trials, helping to gener
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.
Visit our pressroom