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
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 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.
TROPION-Breast01 enrolled 732 patients in Africa,
Asia, Europe, North America and South America. For more information
visit ClinicalTrials.gov.
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 and Datroway 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 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 and
follow the Company on social media @AstraZeneca.
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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.
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
