# EDGAR Filing Document

**Accession Number:** 0000901832
**File Stem:** 0001654954-25-011461
**Filing Date:** 2025-10
**Character Count:** 17838
**Document Hash:** 0c4a03665c7bd53dd6f484d74bfa885f
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001654954-25-011461.hdr.sgml**: 20251006

**ACCESSION NUMBER**: 0001654954-25-011461

**CONFORMED SUBMISSION TYPE**: 6-K

**PUBLIC DOCUMENT COUNT**: 1

**CONFORMED PERIOD OF REPORT**: 20251006

**FILED AS OF DATE**: 20251006

**DATE AS OF CHANGE**: 20251006

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** ASTRAZENECA PLC
- **CENTRAL INDEX KEY:** 0000901832
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 000000000
- **STATE OF INCORPORATION:** X0
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 6-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-11960
- **FILM NUMBER:** 251375606

**BUSINESS ADDRESS:**
- **ADDRESS IS A NON US LOCATION:** YES
- **STREET 1:** 1 FRANCIS CRICK AVENUE
- **STREET 2:** CAMBRIDGE BIOMEDICAL CAMPUS
- **CITY:** CAMBRIDGE
- **PROVINCE COUNTRY:** X0
- **ZIP:** CB2 0AA
- **BUSINESS PHONE:** 011 44 20 7304 5000

**MAIL ADDRESS:**
- **ADDRESS IS A NON US LOCATION:** YES
- **STREET 1:** 1 FRANCIS CRICK AVENUE
- **STREET 2:** CAMBRIDGE BIOMEDICAL CAMPUS
- **CITY:** CAMBRIDGE
- **PROVINCE COUNTRY:** X0
- **ZIP:** CB2 0AA

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** ZENECA GROUP PLC
- **DATE OF NAME CHANGE:** 19930422

**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

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;

 ***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.<sup>1</sup> Chemotherapy remains the 1st-line standard of care for these patients.<sup>2</sup>

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. <u>TROPION-Breast03</u> is evaluating *Datroway* with or without *Imfinzi* (durvalumab) in patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. <u>TROPION-Breast04</u> 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. <u>TROPION-Breast05</u> is evaluating 1st-line *Datroway* with or without *Imfinzi* in patients with metastatic TNBC whose tumours express PD-L1.

 **<u>Notes</u>**

 **Triple-negative breast cancer**

TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.<sup>3,4</sup> TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.<sup>5-7</sup> 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.<sup>5,8,9</sup>

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

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

 **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 <u>ClinicalTrials.gov</u>.

 ***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 <u>TROPION-Breast01</u> 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 <u>TROPION-Lung05</u> and <u>TROPION-Lung01</u> 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 <u>March 2019</u> and *Datroway* in <u>July 2020</u>, 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 <u>astrazeneca.com</u> and follow the Company on social media <u>@AstraZeneca</u>.

 **Contacts**

For details on how to contact the Investor Relations Team, please click <u>here</u>. For Media contacts, click <u>here</u>.

 **References**

&nbsp;&nbsp;&nbsp;&nbsp; 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.

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

&nbsp;&nbsp;&nbsp;&nbsp; 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.

&nbsp;&nbsp;&nbsp;&nbsp; 4. World Health Organization. Breast Cancer. Available at: <u>https://www.who.int/news-room/fact-sheets/detail/breast-cancer</u> Accessed October 2025.

&nbsp;&nbsp;&nbsp;&nbsp; 5. American Cancer Society. Triple-Negative Breast Cancer. Available at: <u>https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/triple-negative.html</u>. Accessed October 2025.

&nbsp;&nbsp;&nbsp;&nbsp; 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

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

&nbsp;&nbsp;&nbsp;&nbsp; 8. National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Available at: <u>https://seer.cancer.gov/statfacts/html/breast-subtypes.html</u>. Accessed October 2025.

&nbsp;&nbsp;&nbsp;&nbsp; 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.

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

&nbsp;&nbsp;&nbsp;&nbsp; 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.

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

&nbsp;&nbsp;&nbsp;&nbsp; 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.

&nbsp;&nbsp;&nbsp;&nbsp; 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**

 <u>SIGNATURES</u>

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

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| By: /s/ Matthew Bowden |
| Name: Matthew Bowden |
| Title: Company Secretary |

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