FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of October 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Datroway improved OS and PFS in TROPION-Breast02
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 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 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 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.
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 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 and TROPION-Lung01 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 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 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 and
follow the Company on social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
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 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 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. 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. 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
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
|
|
AstraZeneca
PLC
|
Date: 06 October 2025
|
|
By: /s/
Matthew Bowden
|
|
|
Name:
Matthew Bowden
|
|
|
Title:
Company Secretary
|