REG - AstraZeneca PLC - Datroway improved OS and PFS in TROPION-Breast02

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RNS Number : 0940C  AstraZeneca PLC  06 October 2025

6 October 2025

 

Datroway demonstrated statistically significant and clinically meaningful
improvement in overall survival as 1st-line therapy for patients with
metastatic triple-negative breast cancer for whom immunotherapy was not an
option in TROPION-Breast02

 

AstraZeneca and Daiichi Sankyo's Datroway is the first and only therapy to
significantly improve overall survival vs. chemotherapy in this patient
population

 

Datroway also demonstrated a highly statistically significant and clinically
meaningful

improvement in the dual primary endpoint of progression-free survival

 

Positive high-level results from the TROPION-Breast02 Phase III trial showed
Datroway (datopotamab deruxtecan) demonstrated a statistically significant and
clinically meaningful improvement for the dual primary endpoints of overall
survival (OS) and progression-free survival (PFS) compared to investigator's
choice of chemotherapy as 1st-line treatment for patients with locally
recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for
whom immunotherapy was not an option.

 

Approximately 70% of patients with metastatic TNBC are not candidates for
immunotherapy, including all patients whose tumours do not express PD-L1 as
well as patients with PD-L1 expressing tumours who cannot receive
immunotherapy due to other factors.(1) Chemotherapy remains the 1st-line
standard of care for these patients.(2)

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "TROPION-Breast02 is the only trial ever to show an overall
survival benefit in the first-line treatment of patients with metastatic
triple-negative breast cancer for whom immunotherapy is not an option. We
expect today's results will mark an inflection point in the treatment of these
patients who have the poorest prognosis of any type of breast cancer and
urgently need better options."

 

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "Datroway is the
first antibody drug conjugate and the only therapy to significantly improve
overall survival compared to chemotherapy in patients with metastatic
triple-negative breast cancer for whom immunotherapy is not an option. These
landmark results from TROPION-Breast02 strengthen our confidence in our
ongoing clinical development programme for Datroway in triple-negative breast
cancer and other tumour types. We look forward to discussing these data with
global regulatory authorities and to bringing Datroway to patients with
triple-negative breast cancer as soon as possible."

 

The safety profile of Datroway was consistent with previous clinical trials of
Datroway in breast cancer. These data will be presented at an upcoming medical
meeting and shared with regulatory authorities.

 

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

 

AstraZeneca and Daiichi Sankyo are evaluating Datroway across stages and
treatment settings of TNBC in three additional Phase III trials.
TROPION-Breast03
(https://clinicaltrials.gov/study/NCT05629585?term=TROPION-Breast03&rank=1)
is evaluating Datroway with or without Imfinzi (durvalumab) in patients with
Stage I-III TNBC with residual invasive disease after neoadjuvant systemic
therapy. TROPION-Breast04
(https://clinicaltrials.gov/study/NCT06112379?term=TROPION-Breast04&rank=1)
is evaluating neoadjuvant Datroway plus Imfinzi in patients with Stage II-III
triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast
cancer. TROPION-Breast05
(https://clinicaltrials.gov/study/NCT06103864?term=TROPION-Breast05&rank=1)
is evaluating 1st-line Datroway with or without Imfinzi in patients with
metastatic TNBC whose tumours express PD-L1.

 

Notes

 

Triple-negative breast cancer

TNBC accounts for approximately 15% of all breast cancer cases, with an
estimated 345,000 diagnoses globally each year.(3,4) TNBC is diagnosed more
frequently in younger and premenopausal women, and is more prevalent in Black
and Hispanic women.(5-7) Metastatic TNBC is the most aggressive type of breast
cancer and has the worst prognosis, with median overall survival of just 12 to
18 months and only about 14% of patients living five years following
diagnosis.(5,8,9)

 

While some breast cancers may test positive for oestrogen receptors,
progesterone receptors or overexpression of HER2, TNBC tests negative for all
three.(5) Due to its aggressive nature and absence of common breast cancer
receptors, TNBC is characteristically difficult to treat.(5) For patients with
metastatic disease with PD-L1 expressing tumours, the addition of
immunotherapy to chemotherapy has improved outcomes in the 1st-line
setting.(10,11) However, for the approximately 70% of patients with metastatic
TNBC who are not candidates for immunotherapy, chemotherapy remains the
1st-line standard of care.(1,2)

 

TROP2 is a protein broadly expressed in several solid tumours including
TNBC.(12) TROP2 is associated with increased tumour progression and poor
survival in patients with breast cancer.(13,14)

 

TROPION-Breast02

TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III
trial evaluating the efficacy and safety of Datroway versus investigator's
choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin
or eribulin) in patients with previously untreated locally recurrent
inoperable or metastatic TNBC for whom immunotherapy was not an option. This
included patients whose tumours did not express PD-L1 as well as patients with
PD-L1 expressing tumours who could not receive immunotherapy due to prior
exposure in early-stage disease, comorbidities or immunotherapy not being
accessible in their geography. Enrolment included patients with de novo or
recurrent disease, regardless of disease-free interval, and those with poor
prognostic factors such as brain metastases.

 

The dual primary endpoints of TROPION-Breast02 are PFS as assessed by blinded
independent central review and OS. Key secondary endpoints include PFS as
assessed by investigator, objective response rate, duration of response,
disease control rate, pharmacokinetics and safety.

 

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North
America and South America. For more information, visit ClinicalTrials.gov
(https://www.clinicaltrials.gov/ct2/show/NCT05374512?term=TROPION&draw=2&rank=8)
.

 

Datroway

Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only)
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 is approved in more than 35 countries/regions worldwide 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 results from the TROPION-Breast01
(https://www.clinicaltrials.gov/study/NCT05104866) trial.

 

Datroway is available in the US under accelerated approval for the treatment
of adult patients with locally advanced or metastatic EGFR-mutated non-small
cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and
platinum-based chemotherapy based on results from the TROPION-Lung05
(https://clinicaltrials.gov/study/NCT04484142) and TROPION-Lung01
(https://clinicaltrials.gov/study/NCT04656652) trials. Continued approval for
this indication in the US may be contingent upon verification and description
of clinical benefit in a confirmatory trial. Datroway is approved in Russia
for the same population.

 

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 NSCLC, TNBC and urothelial cancer. The programme includes
eight 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 in March 2019
(https://www.daiichisankyo.com/media/press_release/detail/index_3199.html) and
Datroway in July 2020
(https://www.daiichisankyo.com/media/press_release/detail/index_3126.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
challenging, and redefining, 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, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes
in previously treated HER2-positive, HER2-low and HER2-ultralow 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 (fulvestrant) and Zoladex (goserelin)
and aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway, and
next-generation oral SERD and potential new medicine camizestrant.

 

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. AstraZeneca is also
exploring the potential of saruparib, a potent and selective inhibitor of
PARP1, in combination with camizestrant in BRCA-mutated, HR-positive,
HER2-negative advanced breast cancer.

 

To bring much-needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with
Daiichi Sankyo to evaluate the potential of Datroway alone and in
combination with immunotherapy Imfinzi. 

 

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
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.

 

References

1.   Punie, et al. Unmet Need for Previously Untreated Metastatic
Triple-Negative Breast Cancer: a Real-World Study of Patients Diagnosed from
2011 to 2022 in the United States. The Oncologist. 2025; 30(3): oyaf034.

2.   National Comprehensive Cancer Network. Breast Cancer. (Version 3.2025).
https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
(https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf)
Accessed October 2025.

3.   O'Reilly D, et al. Overview of Recent Advances in Metastatic Triple
Negative Breast Cancer. World J Clin Oncol. 2021;12(3):164-182.

4.   World Health Organization. Breast Cancer. Available at:
https://www.who.int/news-room/fact-sheets/detail/breast-cancer
(https://www.who.int/news-room/fact-sheets/detail/breast-cancer) Accessed
October 2025.

5.   American Cancer Society. Triple-Negative Breast Cancer. Available at:
https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/triple-negative.html
(https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/triple-negative.html)
. Accessed October 2025.

6.   Martinez et al. Contribution of Clinical and Socioeconomic Factors to
Differences in Breast Cancer Subtype and Mortality Between Hispanic and
Non-Hispanic White Women. Breast Cancer Res Treat. 2017; 166(1):185-193

7.   Vargas et al. Risk Factors for Triple-Negative Breast Cancer Among
Latina Women. Cancer Epidemiol Biomarkers Prev (2019) 28 (11): 1771-1783.

8.   National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer
Subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) . Accessed
October 2025.

9.   Sharma P, et al. Biology and Management of Patients with
Triple-Negative Breast Cancer. Oncologist. 2016; 21(9): 1050-62.
10.1634/theoncologist.2016.0067.

10.  Cortes J, et al. Pembrolizumab Plus Chemotherapy in Advanced
Triple-Negative Breast Cancer. N Engl J Med. 2022;387:217-226.

11.  Geurts V, et al. Immunotherapy for Metastatic Triple Negative Breast
Cancer: Current Paradigm and Future Approaches. Curr Treat Options Oncol.
2023; 24:628-643.

12.  Rossi V, et al. Sacituzumab Govitecan in Triple-Negative Breast Cancer:
from Bench to Bedside, and Back Front Immunol. 2024 Aug;15: 1447280.

13.  Lin H, et al. Significantly upregulated TACSTD2 and Cyclin D1 Correlate
with Poor Prognosis of Invasive Ductal Breast Cancer. Exp Mol Pathol.
2013:94(1): 73-78.

14.  Goldenberg D, et al. The Emergence of Trophoblast Cell-Surface Antigen 2
(TROP-2) as a Novel Cancer Target. Oncotarget. 2018;9(48): 28989-29006.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

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