REG - AstraZeneca PLC - Dato-DXd approved in US for HR+ breast cancer

AstraZenecaAnnouncement

20/01/2025 07:00

For best results when printing this announcement, please click on link below:
https://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20250120:nRST8553Ta&default-theme=true

RNS Number : 8553T  AstraZeneca PLC  20 January 2025

 

 

20 January 2025

 

Datroway (datopotamab deruxtecan) approved in the US for patients with

previously treated metastatic HR-positive, HER2-negative breast cancer

 

First approval in the US for AstraZeneca and Daiichi Sankyo's Datroway based
on TROPION-Breast01 results showing 37% reduction in the risk of disease
progression or death vs. chemotherapy

 

Datroway is the eighth new medicine of the 20 AstraZeneca has set out to
deliver by 2030

 

Datroway (datopotamab deruxtecan or Dato-DXd) has been approved in the US for
the treatment of adult patients with unresectable or metastatic hormone
receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast
cancer who have received prior endocrine-based therapy and chemotherapy for
unresectable or metastatic disease. The approval by the US Food and Drug
Administration (FDA) was based on results from the TROPION-Breast01
(https://clinicaltrials.gov/study/NCT05104866) Phase III trial.

 

Aditya Bardia, MD, MPH, Program Director of Breast Oncology and Director of
Translational Research Integration at the UCLA Health Jonsson Comprehensive
Cancer Center and Global Principal Investigator for TROPION-Breast01, said:
"Despite considerable progress in the HR-positive, HER2-negative metastatic
breast cancer treatment landscape, new therapies are still needed to tackle
the frequent and complex challenge of disease progression after endocrine and
initial chemotherapy. The approval of datopotamab deruxtecan, a novel
TROP2-directed antibody drug conjugate, marks a major therapeutic milestone
and provides patients with metastatic breast cancer a new treatment
alternative to conventional chemotherapy."

 

Dave Fredrickson, Executive Vice President, Oncology Haematology Business
Unit, AstraZeneca, said: "With this first approval of Datroway in the US, we
continue to deliver on our ambition for antibody drug conjugates to improve
upon and replace conventional chemotherapy for the treatment of multiple
cancers. We are proud to bring Datroway to people living with metastatic
HR-positive, HER2-negative breast cancer, and this approval marks the eighth
new medicine of the 20 we have set out to deliver across AstraZeneca by 2030."

 

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi
Sankyo, Inc., said: "The approval of Datroway provides patients with
HR-positive, HER2-negative breast cancer previously treated with
endocrine-based therapy and traditional chemotherapy with the opportunity to
be treated with a new TROP2-directed antibody drug conjugate earlier in the
metastatic setting. Datroway is the latest addition to our portfolio of
innovative cancer treatments and marks the fourth medicine from our oncology
pipeline to receive approval in the US."

 

Caitlin Lewis, Senior Vice President of Strategy & Mission, Living Beyond
Breast Cancer, said: "Only one in three patients with metastatic HR-positive,
HER2-negative breast cancer live more than five years following diagnosis,
highlighting the urgent need for additional effective therapies. The approval
of Datroway is a significant advance, offering patients with metastatic
HR-positive breast cancer a new and much-needed treatment option."

 

In TROPION-Breast01, Datroway significantly reduced the risk of disease
progression or death by 37% compared to investigator's choice of chemotherapy
(hazard ratio  HR  0.63; 95% confidence interval  CI  0.52-0.76; p<0.0001)
in patients with HR-positive, HER2-negative metastatic breast cancer as
assessed by blinded independent central review (BICR). Median progression-free
survival (PFS) was 6.9 months in patients treated with Datroway versus 4.9
months with chemotherapy.

 

The safety profile of Datroway was consistent with the known profile of this
medicine with no new safety concerns identified. In the Datroway arm, the
interstitial lung disease (ILD) rate was 4.2% and the majority of events were
low grade.

 

Datroway is a specifically engineered TROP2-directed antibody drug conjugate
(ADC) discovered by Daiichi Sankyo and being jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.

 

Additional regulatory submissions for Datroway in breast cancer are under
review in the EU, China and other regions.

 

Notes

 

HR-positive breast cancer

In the US, more than 300,000 cases of breast cancer are diagnosed annually.(1)
While survival rates are high for those diagnosed with early breast cancer,
only about 30% of patients diagnosed with or who progress to metastatic
disease are expected to live five years following diagnosis.(2)

 

Approximately 70% of diagnosed cases are considered what has been historically
called HR-positive, HER2-negative breast cancer (measured as HER2 score of IHC
0, IHC 1+ or IHC 2+/ISH-).(2) Endocrine therapies are widely given
consecutively in the early lines of treatment for HR-positive metastatic
breast cancer.(3) However, after initial treatment, further efficacy from
endocrine therapy is often limited.(3) The current standard of care following
endocrine therapy is chemotherapy, which is associated with poor response
rates and outcomes.(3-6)

 

TROPION-Breast01

TROPION-Breast01
(https://clinicaltrials.gov/ct2/show/NCT05104866?term=TROPION-Breast01&draw=2&rank=1)
is a global, randomised, multicentre, open-label Phase III trial evaluating
the efficacy and safety of intravenous Datroway (6 mg/kg) once per 21-day
cycle versus investigator's choice of single-agent chemotherapy (eribulin,
capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable
or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast
cancer who have progressed on and are not suitable for endocrine therapy per
investigator assessment and have received at least one prior line of
chemotherapy for unresectable or metastatic disease.

 

Following disease progression or discontinuation of Datroway or chemotherapy,
patients had the option to receive a subsequent treatment at the discretion of
their physician. Crossover between trial arms was not permitted.

 

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and
OS. Key secondary endpoints include ORR, duration of response,
investigator-assessed PFS, disease control rate, time to first subsequent
therapy and safety. The PFS data and additional results for key secondary
endpoints of TROPION-Breast01 were published in the Journal of Clinical
Oncology (https://ascopubs.org/doi/10.1200/JCO.24.00920) .

 

TROPION-Breast01 enrolled 732 patients in Africa, Asia, Europe, North America
and South America. For more information visit ClinicalTrials.gov
(https://clinicaltrials.gov/study/NCT05104866) .

 

Datroway

Datroway (datopotamab deruxtecan-dlnk in the US; datopotamab deruxtecan in
rest of world) is a TROP2-directed ADC. Designed using Daiichi Sankyo's
proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the
oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes
in AstraZeneca's ADC scientific platform. Datroway is comprised of a humanised
anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo
Medical University, attached to a number of topoisomerase I inhibitor payloads
(an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

 

Datroway (6mg/kg) is approved in the US and Japan for the treatment of adult
patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0,
IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based
therapy and chemotherapy for unresectable or metastatic disease based on the
results from the TROPION-Breast01 Phase III trial.

 

Datroway clinical development programme

A comprehensive global clinical development programme is underway with more
than 20 trials evaluating the efficacy and safety of Datroway across multiple
cancers, including non-small cell lung cancer, triple-negative breast cancer
(TNBC) and HR-positive, HER2-negative breast cancer. The programme includes
seven Phase III trials in lung cancer and five Phase III trials in breast
cancer evaluating Datroway as a monotherapy and in combination with other
anticancer treatments in various settings.

 

Daiichi Sankyo collaboration

AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly
develop and commercialise Enhertu (trastuzumab deruxtecan) in March 2019
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html#!)
and Datroway in July 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html#!)
, except in Japan where Daiichi Sankyo maintains exclusive rights for each
ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu
and Datroway.

 

AstraZeneca in breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is
starting to challenge, and redefine, the current clinical paradigm for how
breast cancer is classified and treated to deliver even more effective
treatments to patients in need - with the bold ambition to one day eliminate
breast cancer as a cause of death.

 

AstraZeneca has a comprehensive portfolio of approved and promising compounds
in development that leverage different mechanisms of action to address the
biologically diverse breast cancer tumour environment.

 

With Enhertu, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming
to improve outcomes in previously treated HER2-positive and HER2-low
metastatic breast cancer and are exploring its potential in earlier lines of
treatment and in new breast cancer settings.

 

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with
foundational medicines Faslodex and Zoladex (goserelin) and aims to
reshape the HR-positive space with first-in-class AKT inhibitor, Truqap
(capivasertib), and next-generation SERD and potential new medicine
camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore
the potential of TROP2-directed ADC, Datroway, in this setting.

 

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has
been studied in early and metastatic breast cancer patients with an inherited
BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and
Canada) continue to research Lynparza in these settings and to explore its
potential in earlier disease.

 

To bring much-needed treatment options to patients with TNBC, an aggressive
form of breast cancer, AstraZeneca is evaluating the potential of Datroway
alone and in combination with
immunotherapy Imfinzi (durvalumab), Truqap in combination with
chemotherapy, and Imfinzi in combination with other oncology medicines,
including Lynparza and Enhertu.

 

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand cancer and
all its complexities to discover, develop and deliver life-changing medicines
to patients.

 

The Company's focus is on some of the most challenging cancers. It is through
persistent innovation that AstraZeneca has built one of the most diverse
portfolios and pipelines in the industry, with the potential to catalyse
changes in the practice of medicine and transform the patient experience.

 

AstraZeneca has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.

 

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (https://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/) .

 

Contacts
For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   American Cancer Society. Key Statistics for Breast Cancer. Available
at:
https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html.
Accessed January 2025.

2.   National Cancer Institute. Surveillance, Epidemiology and End Results
Program. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) . Accessed
January 2025.

3.   Manohar P, et al. Updates in endocrine therapy for metastatic breast
cancer. Cancer Biol Med. 2022 Feb 15; 19(2):202-212.

4.   Cortes J, et al. Eribulin monotherapy versus treatment of physician's
choice in patients with metastatic breast cancer (EMBRACE): a phase 3
open-label randomised study. Lancet. 2011;377:914-923.

5.   Yuan P, et al. Eribulin mesilate versus vinorelbine in women with
locally recurrent or metastatic breast cancer: A randomised clinical
trial. Eur J Cancer. 2019;112:57-65.

6.     Jerusalem G, et al. Everolimus Plus Exemestane vs Everolimus or
Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative
Advanced Breast Cancer. JAMA Oncol. 2018;4(10):1367-1374.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  REAUBRARVKUAAUR