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 August 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu improved PFS in 1L HER2m lung cancer
17 August 2026
Enhertu demonstrated
statistically significant and clinically meaningful improvement in
progression-free survival as 1st-line treatment of patients with
HER2-mutant advanced non-small cell lung cancer
in
DESTINY-Lung04 Phase III trial
AstraZeneca and Daiichi Sankyo's Enhertu is the first and
only
HER2-directed medicine to improve progression-free
survival
over global standard of care in a Phase III trial in this
setting
Positive high-level results from the DESTINY-Lung04 Phase III trial
showed Enhertu (trastuzumab deruxtecan) demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) versus global standard of care
(platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as
1st-line treatment of patients with unresectable, locally advanced
or metastatic HER2-mutant non-squamous non-small cell lung cancer
(NSCLC). The trial will continue as planned to evaluate
secondary endpoints including overall survival.
The global standard of care for patients
with HER2-mutant NSCLC in the 1st-line metastatic setting is
a combination of immunotherapy and platinum-based
chemotherapy.1-3 However,
many patients do not respond to 1st-line treatment and experience
disease progression, underscoring the need for additional treatment
options.3-7 Approximately
2-4% of patients with NSCLC have tumours with
a HER2 mutation.8-10
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "Our oncology pipeline continues
to advance with DESTINY-Lung04 becoming the first Phase III trial
to demonstrate a progression-free survival benefit versus the
global standard of care in this first-line setting, supporting the
potential for Enhertu to move earlier in the treatment
of HER2-mutant non-small cell lung cancer. This
aggressive lung cancer often affects younger patients and has
historically had limited first-line targeted treatment options,
making these positive results an important step forward in bringing
additional effective therapies to patients at metastatic diagnosis
when there is the greatest opportunity to improve outcomes."
John Tsai, Global Head, R&D, Daiichi Sankyo, said:
"Enhertu is already established as the first and only
antibody drug conjugate for the second-line treatment
of HER2-mutant metastatic non-small cell lung cancer. The
positive results seen in DESTINY-Lung04 show that treatment
with Enhertu in the first-line setting delays disease
progression compared to the global standard of care, highlighting
its potential to improve outcomes for patients earlier in the
treatment of metastatic disease."
The safety profile of Enhertu observed in DESTINY-Lung04 was generally
consistent with its known profile, with no new safety concerns
identified.
The DESTINY-Lung04 data will be presented at a forthcoming medical
meeting and shared with global regulatory authorities.
Enhertu is currently
approved to treat patients with previously treated metastatic NSCLC
whose tumours have activating HER2 (ERBB2) mutations, and to treat patients with
HER2-positive solid tumours, including HER2-overexpressing
metastatic NSCLC, who have received prior treatment and who have no
satisfactory treatment options.
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.
Notes
HER2-mutant NSCLC
Lung cancer is the most commonly diagnosed cancer globally and
remains the leading cause of cancer-related death in both men and
women.11 In
2024, approximately 2.6 million new lung cancer cases were reported
worldwide, with an estimated 1.8 million deaths.11 NSCLC
is the most common type of lung cancer, accounting for
approximately 85% of cases.12 Prognosis
is particularly poor for patients with metastatic NSCLC as only
approximately 10% will live beyond five years after
diagnosis.13-15
HER2 is a tyrosine kinase receptor protein involved in cell growth
and differentiation and expressed on the surface of multiple tumour
types. HER2 mutations have been identified in NSCLC as
distinct molecular targets and have been reported in approximately
2-4% of patients with non-squamous NSCLC.8-10 These HER2 mutations
are predominantly seen in younger women and people with no smoking
history and have been independently associated with cancer cell
growth and poor prognosis, with an increased incidence of brain
metastases.8,16-20
The global standard of care in the 1st-line metastatic setting for
patients with HER2-mutant NSCLC is a combination of immunotherapy and
platinum-based chemotherapy.1-3 While
these treatment regimens have been shown to improve survival in
NSCLC, many patients do not respond to 1st-line treatment and
experience disease progression, underscoring the need for
additional treatment options.3-7
DESTINY-Lung04
DESTINY-Lung04 is a global, randomised, open-label, Phase III trial
evaluating the efficacy and safety of Enhertu (5.4mg/kg) compared to standard of care
(platinum-pemetrexed doublet chemotherapy in combination with
pembrolizumab) in patients with unresectable, locally advanced or
metastatic, non-squamous NSCLC harbouring
a HER2 exon
19 or 20 mutation.
Patients were randomised 1:1 to receive
either Enhertu or standard of care. Randomisation was
stratified by smoking history and presence or history of brain
metastasis. The primary endpoint of DESTINY-Lung04 is PFS as
assessed by blinded independent central review (BICR). Secondary
endpoints include OS, investigator-assessed PFS, overall response
rate and duration of response as assessed by BICR and investigator,
pharmacokinetics and safety.
DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia,
Europe and North America. For more information about the trial,
visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed
ADC. Designed using the proprietary DXd ADC Technology of Daiichi
Sankyo, 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)
followed by THP is approved in the US, China, Singapore and India
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) is
approved in Brazil and 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) in
combination with pertuzumab is approved in more than ten countries
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 75 countries 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 100 countries 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 100 countries 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 80 countries 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 90 countries 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 45 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 in the US 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 lung cancer
AstraZeneca is working to bring patients with lung cancer closer to
cure through the detection and treatment of early-stage disease,
while also pushing the boundaries of science to improve outcomes in
the resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit
most.
The Company's comprehensive portfolio includes leading lung cancer
medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab)
and Imjudo (tremelimumab); Enhertu (trastuzumab
deruxtecan) and Datroway in
collaboration with Daiichi Sankyo; Orpathys in
collaboration with HUTCHMED; as well as a pipeline of potential new
medicines and combinations across diverse mechanisms of
action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a
global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer, including and
beyond treatment.
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
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Oncogene-addicted metastatic non-small-cell lung cancer: ESMO
Clinical Practice Guideline for diagnosis, treatment and
follow-up. Ann Oncol. 2023;34(4):339-357.
2. National Comprehensive Cancer
Network. NCCN Clinical Practice Guidelines in Oncology. Version
5.2026. March 13, 2026. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
Accessed August 2026.
3. Man J, et al. Response Rate and
Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in
PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC
Trials. JNCI Cancer Spectr. 2021;5(3):pkab012.
4. Paz-Ares L, et al. A
Randomized, Placebo-Controlled Trial of Pembrolizumab Plus
Chemotherapy in Patients With Metastatic Squamous NSCLC:
Protocol-Specified Final Analysis of
KEYNOTE-407. J Thorac
Oncol. 2020
Oct;15(10):1657-1669.
5. Mok TSK, et al. Pembrolizumab
versus chemotherapy for previously untreated, PD-L1-expressing,
locally advanced or metastatic non-small-cell lung cancer
(KEYNOTE-042): a randomised, open-label, controlled, phase 3
trial. Lancet. 2019 May
4;393(10183):1819-1830.
6. Rodríguez-Abreu D et
al. Pemetrexed plus platinum with or without pembrolizumab in
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KEYNOTE-189. Ann Onc. 2021 Jul;32(7):881-895.
7. Brahmer J.R. et
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patients (pts) with metastatic NSCLC and PD-L1 tumour proportion
score (TPS) ≥50%. ESMO 2021 Virtual
Congress; Abstract
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8. Mazieres J, et al. Lung Cancer That
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9. cBioPortal for Cancer Genomics.
Available at: https://www.cbioportal.org/.
Accessed August 2026.
10. Yoshizawa A, et al. HER2 Status In Lung
Adenocarcinoma: A Comparison Of Immunohistochemistry, Fluorescence
In Situ Hybridization (FISH), Dual-ISH, and Gene
Mutations. Lung Cancer. 2014;85(3):373-378.
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World Health Organization. Lung Cancer Fact Sheet. Available at:
https://gco.iarc.who.int/today/en/fact-sheets-cancers/15/trachea-bronchus-and-lung.
Accessed August 2026.
12. Leiter A, et al. The global
burden of lung cancer: current status and future
trends. Nat Rev Clin
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13. Tamura T, et al. Specific organ
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14. Goldstraw P, et al. The IASLC Lung
Cancer Staging Project: Proposals for Revision of the TNM Stage
Groupings in the Forthcoming (Eighth) Edition of the TNM
Classification for Lung Cancer. J Thorac
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15. Siegel RL, et al. Cancer Statistics,
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16. Liu S, et al. Targeting HER2 Aberrations
in Non-Small Cell Lung Cancer with
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2018;24(11):2594-2604.
17. Stephens P, et al. Lung cancer:
intragenic ERBB2 kinase mutations in
tumours. Nature. 2004;431:525-6.
18. Arcila ME, et al. Prevalence,
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(HER2) Tyrosine Kinase Mutations in Lung
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19. Pillai RN, et
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20. Offin M, et al. Frequency and
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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:
17 August 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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