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 May 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1. Enhertu
approved in two HER2+ early BC settings
18 May 2026
Enhertu approved in the US for two new indications
for patients with HER2-positive early breast
cancer
Approved for use before surgery based on DESTINY-Breast11 Phase III
trial
Approved for use following surgery based on DESTINY-Breast05 Phase
III trial
Two new indications bring AstraZeneca
and Daiichi Sankyo's Enhertu into curative-intent setting,
reinforcing its role across stages of HER2-positive breast
cancer
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved
by the US Food and Drug Administration (FDA) for both the
neoadjuvant and adjuvant treatment of patients with HER2-positive
early breast cancer based on results from the DESTINY-Breast11 and
DESTINY-Breast05 Phase III trials,
respectively.
In the neoadjuvant setting, Enhertu followed by a taxane, trastuzumab, and
pertuzumab (THP) has been approved for the treatment of adult
patients with HER2-positive Stage II or Stage III breast cancer. In
the adjuvant setting, Enhertu has been approved for the treatment of adult
patients with HER2-positive breast cancer who have residual
invasive disease following trastuzumab (with or without pertuzumab)
and taxane-based treatment.
Shanu Modi, MD, Medical Oncologist, Memorial Sloan Kettering Cancer
Center, said: "HER2-positive breast cancer is an aggressive
disease, and our goal is to reduce the risk of recurrence for
patients as early as possible to achieve the best long-term
outcomes. The neoadjuvant setting offers the earliest opportunity
to improve outcomes, while the adjuvant setting provides another
important chance to prevent recurrence for patients with residual
disease after surgery. These two new indications in HER2-positive
early breast cancer will evolve how we treat patients in these
settings and support trastuzumab deruxtecan as a potential new
standard of care in early-stage disease."
Dave Fredrickson, Executive Vice President, Oncology Haematology
Business Unit, AstraZeneca, said: "HER2-positive early disease is
considered highly curable, however up to one in four patients still
experience disease recurrence, underscoring the need for new
options in this setting. These approvals mark an important
step forward, expanding the possibility of cure to more
patients for the first time in many years and
positioning Enhertu as a foundational treatment in early breast
cancer."
Ken Keller, Global Head of Oncology Business, and President
and CEO, Daiichi Sankyo, Inc. said: "Enhertu has redefined the treatment of
HER2-expressing breast cancer with practice-changing data across
six breast cancer indications in seven
years. Enhertu is now approved in the US across both early
and metastatic HER2-positive breast cancer, accomplishing what we
set out to achieve a little over a decade ago for patients at the
start of our comprehensive clinical development
programme."
Victoria Smart, Senior Vice President, Mission, Susan G. Komen,
said: "Providing patients with early breast cancer more options to
help prevent progression to metastatic disease can lead to improved
outcomes. Progression and recurrence remain among the most
significant unmet needs for those diagnosed with early breast
cancer, and continued advances in treatment bring new hope to
patients and families facing this disease."
In DESTINY-Breast11, Enhertu followed
by THP as a neoadjuvant treatment demonstrated a pathologic
complete response (pCR) rate of 67.3% compared with 56.3% for
dose-dense doxorubicin and cyclophosphamide followed by THP
[ddAC-THP], an improvement of 11.2% (95% confidence interval [CI]
3.9-18.3; p=0.003). At the time of the pCR analysis, 29 patients
(4.5%) had event-free survival (EFS) events, and 12 patients (1.9%)
had overall survival (OS) events. The results were published
in Annals
of Oncology.1
In DESTINY-Breast05, Enhertu as
an adjuvant treatment reduced the risk of invasive disease
recurrence or death (invasive disease-free survival [IDFS]) by 53%
compared to trastuzumab emtansine (T-DM1) in patients with
HER2-positive breast cancer with residual invasive disease
following neoadjuvant therapy (hazard ratio [HR] 0.47; 95% CI
0.34-0.66; p<0.0001). At three years, 92.4% of patients in
the Enhertu arm were
alive and free of invasive disease, compared with 83.7% of those in
the T-DM1 arm, with 51 (6%) events in the Enhertu arm and 102 (12%) in the T-DM1 arm. The
results were published in The
New England Journal of Medicine.2
Data from both trials were presented at the 2025 European Society
for Medical Oncology (ESMO) Congress.
Based on the DESTINY-Breast05 results, trastuzumab deruxtecan
(Enhertu) has been included in the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®)
as a Category 1 recommended treatment in the adjuvant setting for
patients with HER2-positive early breast cancer with residual
disease and a high risk of recurrence following preoperative
therapy. See NCCN Guidelines® for
detailed recommendations.
No new safety concerns were identified
with Enhertu in
the DESTINY-Breast11 or DESTINY-Breast05
trials.
In DESTINY-Breast11, Enhertu followed by THP showed similar rates of
drug-related overall adverse events (AEs) and interstitial lung
disease (ILD)/pneumonitis as ddAC-THP, and lower rates of Grade 3
or higher AEs, serious AEs, AEs leading to treatment interruptions,
left ventricular dysfunction and haematological
toxicities.
In DESTINY-Breast05, Enhertu and T-DM1 showed similar rates of overall
drug-related AEs and Grade 3 or higher AEs. Adjudicated
drug-related ILD/pneumonitis occurred in 9.6% of patients in
the Enhertu arm and 1.6% of patients in the T-DM1 arm.
The majority of ILD/pneumonitis events were low grade in both arms.
There were seven Grade 3 events and two deaths (Grade 5) in
the Enhertu arm.
The DESTINY-Breast11 and DESTINY-Breast05 US regulatory submissions
were both reviewed under Project Orbis, which provides a
framework for concurrent submission and review of oncology
medicines among participating international partners. Separate
regulatory applications for both trials are also under review in
other countries. DESTINY-Breast05 previously
received Priority
Review and Breakthrough
Therapy Designation by the FDA.
Enhertu is already
approved in more than 95 countries, including the US, as a
treatment for patients with HER2-positive metastatic breast
cancer.
Enhertu is a specifically
engineered HER2-directed DXd antibody drug conjugate (ADC)
discovered by Daiichi Sankyo and being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
Financial Considerations
Following these approvals in the US, an amount of $155 million is
due from AstraZeneca to Daiichi Sankyo as milestone
payments for both these indications. Sales
of Enhertu in the US are recognised by Daiichi Sankyo.
For further details on the financial arrangements, please consult
the collaboration agreement from March
2019.
Notes
HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.3 More
than two million breast cancer cases were diagnosed in 2022, with
an estimated 665,000 deaths globally.3 In
the US, more than 320,000 cases of breast cancer are diagnosed
annually with over 42,000 deaths.4
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including breast
cancer.5 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease and
poor prognosis in breast cancer.5 An
estimated one in five cases of breast cancer is considered
HER2-positive.6 Approximately
one in three patients with HER2-positive early-stage breast cancer
is considered high-risk, meaning they are more likely to experience
disease recurrence and have a poor prognosis, and up to one in four
will experience disease recurrence.7,8
HER2-positive early breast cancer is generally treated across two
phases: the neoadjuvant (pre-surgical) phase and the adjuvant or
post-neoadjuvant (post-surgical) phase.
In the neoadjuvant setting, the current standard of care in many
regions of the world involves combination chemotherapy
regimens.9 In
the US, the current standard of care consists
of a combination regimen of carboplatin,
trastuzumab, pertuzumab and a taxane.9,10 For
patients with HER2-positive early breast cancer, achieving pCR,
defined as no evidence of invasive cancer cells in the removed
breast tissue or lymph nodes following treatment with neoadjuvant
treatment, is an early indicator of improved long-term
survival.11 Approximately
half of patients (39-66%) who receive neoadjuvant treatment do not
reach pCR, putting them at increased risk of disease
recurrence.12-16
In the adjuvant setting, despite
receiving additional treatment with current standard of
care for residual disease, some patients still experience invasive
disease or death.17 Once
patients are diagnosed with metastatic disease, the five-year
survival rate drops from nearly 90% to approximately
30%.18
DESTINY-Breast11
DESTINY-Breast11 is a global, multicentre, randomised, open-label,
Phase III trial evaluating the efficacy and safety of
neoadjuvant Enhertu (5.4mg/kg) monotherapy
or Enhertu followed by THP compared to ddAC-THP in
patients with high-risk HER2-positive early-stage breast
cancer.
Patients were randomised 1:1:1 to receive either eight cycles
of Enhertu monotherapy; four cycles
of Enhertu followed by four cycles of THP; or four
cycles of ddAC followed by four cycles of THP.
The Enhertu monotherapy arm was closed early following a
recommendation from the Independent Data Monitoring
Committee.
The primary endpoint of DESTINY-Breast11 is rate of pCR - defined
as no evidence of invasive cancer cells in the removed breast
cancer tissue or lymph nodes following treatment. Secondary
endpoints include EFS, invasive disease-free survival, overall
survival and safety.
DESTINY-Breast11 enrolled 927 patients across multiple sites in
Asia, Europe, North America and South America. For more information
about the trial, visit ClinicalTrials.gov.
DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label,
Phase III trial evaluating the efficacy and safety
of Enhertu (5.4mg/kg) versus T-DM1 in patients with
HER2-positive early breast cancer with residual invasive disease in
breast or axillary lymph nodes following neoadjuvant therapy and a
high risk of recurrence. High risk of recurrence was defined as
presentation with inoperable cancer (prior to neoadjuvant therapy)
or pathologically positive axillary lymph nodes following
neoadjuvant therapy.
Patients were randomised 1:1 to receive 14 cycles
of Enhertu or T-DM1.
The primary endpoint of DESTINY-Breast05 is investigator-assessed
IDFS, which is defined as the time from randomisation until first
invasive local, axillary or distant recurrence or death from any
cause. Secondary endpoints include investigator-assessed DFS,
overall survival, distant recurrence-free interval, brain
metastasis-free interval and safety.
DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North
America, Oceania and South America. For more information about the
trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed
ADC. Designed using Daiichi Sankyo's proprietary DXd ADC
Technology, Enhertu is
the lead ADC in the oncology portfolio of Daiichi Sankyo and the
most advanced programme in AstraZeneca's ADC scientific
platform. Enhertu consists of a HER2 monoclonal antibody
attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers.
Enhertu (5.4mg/kg) is
approved in the US as an adjuvant treatment for adult patients with
HER2-positive (IHC 3+ or ISH+) breast cancer who have residual
invasive disease following trastuzumab (with or without
pertuzumab) and taxane-based treatment based on
the DESTINY-Breast05 trial.
Enhertu (5.4mg/kg)
followed by THP is approved in the US and China as a neoadjuvant
treatment for adult patients with HER2-positive (IHC 3+ or
ISH+) Stage II or III breast cancer based on the results from
the DESTINY-Breast11 trial.
Continued approval in China for this indication may be contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu (5.4mg/kg) in
combination with pertuzumab is approved in the US, Switzerland,
United Arab Emirates and Saudi Arabia as a 1st-line treatment for
adult patients with unresectable or metastatic HER2-positive (IHC
3+ or ISH+) breast cancer based on the results from
the DESTINY-Breast09 trial.
Enhertu (5.4mg/kg) is
approved in more than 95 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic
HER2-positive (IHC 3+ or ISH+) breast cancer who have received a
prior anti-HER2-based regimen, either in the metastatic setting or
in the neoadjuvant or adjuvant setting, and have developed disease
recurrence during or within six months of completing therapy based
on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is
approved in more than 95 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a
prior systemic therapy in the metastatic setting or developed
disease recurrence during or within six months of completing
adjuvant chemotherapy based on the results from
the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is
approved in more than 70 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic hormone
receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or
HER2-ultralow (IHC 0 with membrane staining) breast cancer, as
determined by a locally or regionally authorised test, that have
progressed on one or more endocrine therapies in the metastatic
setting based on the results from the DESTINY-Breast06 trial.
Enhertu (5.4mg/kg) is
approved in more than 75 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic
non-small cell lung cancer (NSCLC) whose tumours have
activating HER2 (ERBB2) mutations, as detected by a locally or
regionally approved test, and who have received a prior systemic
therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials.
Continued approval in China and the US for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial.
Enhertu (6.4mg/kg) is
approved in more than 85 countries/regions worldwide for the
treatment of adult patients with locally advanced or metastatic
HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal
junction (GEJ) adenocarcinoma who have received a prior
trastuzumab-based regimen based on the results from
the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.
Enhertu (5.4mg/kg) is
approved in more than 15 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic
HER2-positive (IHC 3+) solid tumours who have received prior
systemic treatment and have no satisfactory alternative treatment
options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
Enhertu clinical development
programme
A comprehensive global clinical development programme is underway
evaluating the efficacy and safety of Enhertu as a monotherapy, in combination or
sequentially with other cancer medicines across multiple
HER2-targetable cancers.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu in March
2019 and Datroway (datopotamab
deruxtecan) 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 expanding 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 TROP-2-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 (durvalumab).
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/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Disease, 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. Harbeck N, Modi S, Pusztai L, et
al. Neoadjuvant trastuzumab deruxtecan alone or followed by
paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive
early breast cancer (DESTINY-Breast11): a randomised, open-label,
multicentre, phase III trial. Ann Oncol. 2026;37(2):166-179.
2. Loibl S, et al. Trastuzumab
deruxtecan in residual HER2-positive early breast
cancer. N Engl J
Med.
2026;394(9):845-857.
3. World Health Organization.
Available at: Breast Fact
Sheet. Accessed May
2026.
4. Siegel RL, et al. Cancer
statistics, 2026. CA Cancer J
Clin.
2026;76(1):e70043.
5. Cheng X. A comprehensive review of
HER2 in cancer biology and therapeutics. Genes.
(Basel). 2024;15(7):903.
6. Tarantino P, et al. ESMO expert
consensus statements (ECS) on the definition, diagnosis, and
management of HER2-low breast cancer. Ann Oncol. 2023;34(8):645-659.
7. Mahtani R, et al. Human epidermal
growth factor receptor 2-positive (HER2+) early breast cancer
treatment and outcomes by risk of recurrence: a retrospective US
electronic health records study. Cancers
(Basel).
2025;17(9):1848.
8. Joyce O, et al. Risk of recurrence
in patients with HER2+ early-stage breast cancer: Literature
analysis of patient and disease
characteristics. Clinical Breast
Cancer. 2023;23(4):350-362.
9.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer.
Version 2. 2026
10. Wang J, et al. Breast cancer: an
overview of current therapeutic strategies, challenge, and
perspectives. Breast
Cancer.
2023;15:721-730.
11. Spring LM, et al. Pathological
complete response after neoadjuvant chemotherapy and impact on
breast cancer recurrence and survival: a comprehensive
meta-analysis. Clin Cancer
Res.
2020;26(12):2838-2848.
12. Schneeweiss A, et al. Pertuzumab plus
trastuzumab in combination with standard neoadjuvant
anthracycline-containing and anthracycline-free chemotherapy
regimens in patients with HER2-positive early breast cancer: a
randomized phase II cardiac safety study
(TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284.
13. Swain SM, et al. Pertuzumab,
trastuzumab, and standard anthracycline- and taxane-based
chemotherapy for the neoadjuvant treatment of patients with
HER2-positive localized breast cancer (BERENICE): a phase II,
open-label, multicenter, multinational cardiac safety
study. Ann Oncol. 2018;29(3):646-653.
14. Huober J, et al. Atezolizumab with
neoadjuvant anti-human epidermal growth factor receptor 2 therapy
and chemotherapy in human epidermal growth factor receptor
2-positive early breast cancer: primary results of the randomized
phase III IMpassion050 trial. J Clin
Oncol. 2022;40(25):2946-2956.
15. Masuda N, et al. A randomized, 3-arm,
neoadjuvant, phase 2 study comparing
docetaxel + carboplatin + trastuzumab + pertuzumab
(TCbHP), TCbHP followed by trastuzumab emtansine and pertuzumab
(T-DM1+P), and T-DM1+P in HER2-positive primary breast
cancer. Breast Cancer Res
Treat.
2020;180(1):135-146.
16.
Gao HF, et al. De-escalated neoadjuvant taxane plus trastuzumab and
pertuzumab with or without carboplatin in HER2-positive early
breast cancer (neoCARHP): a multicentre, open-label, randomised,
phase 3 trial. Presented at the ASCO Annual Meeting
2025.
17. Geyer CE, et al. Survival with
trastuzumab emtansine in residual HER2-positive breast
cancer. N
Engl J Med.
2025;392(3):249-257.
18. National Cancer Institute. SEER Cancer
Stat Facts: Female Breast Cancer. Available
at: https://seer.cancer.gov/statfacts/html/breast.html. Accessed
May 2026
Disclosure: Dr. Modi provides consulting and advisory services to
AstraZeneca (and Daiichi Sankyo).
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.
Date: 18 May 2026
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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