FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
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the
Securities Exchange Act of 1934
For the
month of June 2026
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in EU for HER2+ solid tumours
29 June 2026
Enhertu approved
in the EU as first tumour agnostic HER2-directed therapy and
antibody drug conjugate for patients with previously treated
HER2-positive metastatic solid tumours
Based on three Phase II trials of AstraZeneca and Daiichi Sankyo's
Enhertu which demonstrated clinically meaningful responses across a
broad range of tumours
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved
in the European Union (EU) as a monotherapy for the treatment of
adult patients with unresectable or metastatic HER2-positive
(immunohistochemistry [IHC] 3+) solid tumours who have received
prior treatment and who have no satisfactory treatment
options.
The approval by the European Commission follows the positive
opinion of the Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA) and is based on
results from a subgroup of patients with HER2-positive (IHC 3+)
tumours across three Phase II trials, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02.
Benedikt Westphalen, MD, Head of the Precision Oncology Program,
Comprehensive Cancer Center of the University of Munich, Germany,
said: "HER2 overexpression occurs across multiple tumour types and
is associated with aggressive disease and a poor prognosis. Until
now, HER2-directed therapies were only available for specific
tumour types. The approval of trastuzumab deruxtecan as a
tumour-agnostic therapy opens a new treatment option for patients
with HER2-positive cancers regardless of where the tumour
originated."
Dave Fredrickson, Executive Vice President, Oncology Haematology
Business Unit, AstraZeneca, said: "Precision medicine is reshaping
cancer care by helping inform treatment decisions based on the
molecular and biological characteristics of a patient's
disease. Enhertu is already approved in breast, gastric,
and lung cancers, and with this approval, clinicians may now
consider Enhertu for
patients with HER2-positive status across multiple
additional tumour types. This highlights the importance
of biomarker testing to identify eligible patients and
ensure that those with HER2-positive disease are
considered for targeted treatment."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, Inc., said: "This approval
of Enhertu marks a significant milestone in the EU for
patients with HER2-positive metastatic solid tumours and
establishes the first tumour-agnostic indication for a
HER2-directed therapy and antibody drug conjugate in the
region. Enhertu is now approved for six indications in the
EU, which demonstrates our commitment to advancing innovative
medicines in areas of high unmet need to patients with cancer."
In the DESTINY-PanTumor02 Phase II trial, Enhertu demonstrated a confirmed objective response
rate (ORR) of 52.3% (95% confidence interval [CI]
42.6-61.8) and median duration of response (DOR) of 21.1
months (95% CI 10.6-25.0) in patients with previously
treated centrally or locally assessed IHC 3+ solid tumours (n=111)
including biliary tract, bladder, cervical, endometrial,
ovarian, pancreatic or other tumours. In
DESTINY-Lung01, Enhertu demonstrated a confirmed ORR of
52.9% (95% CI 27.8-77.0) and median DOR of 6.9
months (95% CI 4.0-9.8) in patients with previously
treated centrally confirmed IHC 3+ non-small cell lung cancer
(NSCLC) (n=17). In DESTINY-CRC02, Enhertu demonstrated a confirmed ORR of
46.9% (95% CI 34.3-59.8) and median DOR of 5.5
months (95% CI 4.2-8.1) in patients with previously
treated centrally confirmed IHC 3+ colorectal cancer
(n=64).
The safety profile of Enhertu was based on a pooled analysis of patients
with unresectable or metastatic HER2-positive (IHC 3+) solid
tumours enrolled in DESTINY-PanTumor02, DESTINY-Lung01,
DESTINY-CRC02 and DESTINY-Breast01, and was consistent with
previous clinical trials, with no new safety concerns
identified.
Enhertu has received a
tumour agnostic indication in the US and other countries based on
the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02
trials.
Additional regulatory submissions for Enhertu are under review in the EU, including in
combination with pertuzumab for the 1st-line treatment of patients
with unresectable or metastatic HER2-positive (IHC 3+ or ISH+)
breast cancer based on data from the DESTINY-Breast09 Phase
III trial and for patients with HER2-positive (IHC 3+ or ISH+)
breast cancer who have residual invasive disease after neoadjuvant
HER2-targeted treatment based on data from
the DESTINY-Breast05 Phase
III trial.
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 this approval in the EU, an amount of $25 million is due from
AstraZeneca to Daiichi Sankyo as a milestone payment for the
tumour-agnostic indication. Sales of Enhertu in most EU territories are recognised by
Daiichi Sankyo. For further details on the financial arrangements,
please consult the collaboration agreement
from March
2019.
Notes
HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of various tissue cells throughout the
body and is involved in normal cell growth.1 HER2
protein overexpression may occur as a result
of HER2 gene amplification and is often associated
with aggressive disease and poor prognosis in some
cancers.2 HER2
overexpression occurs in a range of solid tumours with the
prevalence varying by tumour type.3
HER2-directed therapies have been used to treat HER2 overexpression
in breast, gastric and biliary tract cancers in the
EU.1,4-6 Although
HER2 is overexpressed in additional solid tumour types including
lung, bladder, cervical, colorectal, endometrial, ovarian, salivary
gland and pancreatic cancers, HER2 testing is not routinely
performed for these additional tumour types and prior to this
approval there were no HER2-directed treatments approved in the EU
to treat a broad range of solid tumours.2,3,7,
DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort,
open-label, Phase II trial evaluating the efficacy and safety
of Enhertu (5.4mg/kg) for the treatment of previously
treated HER2-expressing tumours, including biliary tract, bladder,
cervical, endometrial, ovarian, pancreatic cancer or other
tumours.
The primary endpoint of DESTINY-PanTumor02 is confirmed ORR as
assessed by investigator. Secondary endpoints include DOR, disease
control rate (DCR), progression-free survival (PFS), overall
survival (OS), safety, tolerability and pharmacokinetics. Results
from DESTINY-PanTumor02 were published in
the Journal
of Clinical Oncology.8
DESTINY-PanTumor02 enrolled 267 HER2-positive (IHC 3+ [n=111] and
IHC 2+ [n=156]) adult patients at multiple sites in Asia, Europe,
North America, South America and Oceania. For more information
about the trial, visit ClinicalTrials.gov.
DESTINY-Lung01
DESTINY-Lung01 is a global, open-label, two-cohort, Phase II trial
evaluating the efficacy and safety of Enhertu (5.4mg/kg or 6.4mg/kg) in patients
with HER2-mutant or HER2-overexpressing unresectable or
metastatic NSCLC who had progressed after one or more systemic
therapies.
The primary endpoint of DESTINY-Lung01 is confirmed ORR by
independent central review. Key secondary endpoints include DOR,
DCR, PFS, OS and safety. Results from the HER2-mutant cohort were published
in The
New England Journal of Medicine and results from the HER2-overexpressing
cohort were published in The
Lancet Oncology.9,10
DESTINY-Lung01 enrolled 181 adult patients (HER2-mutant [n=91] and
HER2-overexpressing [n=90; IHC 3+, n=17 and IHC 2+, n=73]) at
multiple sites in Asia, Europe and North America. For more
information about the trial, visit ClinicalTrials.gov.
DESTINY-CRC02
DESTINY-CRC02 is a global, randomised, two-arm, parallel,
multicentre, Phase II trial evaluating the efficacy and safety of
two doses (5.4mg/kg or 6.4mg/kg) of Enhertu in patients with locally advanced,
unresectable or metastatic HER2-positive (IHC 3+ or IHC 2+)
colorectal cancer of BRAF wild-type, RAS wild-type or RAS mutant
tumour types previously treated with standard therapy. The trial
was conducted in two stages. In the first stage, patients (n=80)
were randomised 1:1 to receive either 5.4mg/kg or 6.4mg/kg
of Enhertu. In the second stage, additional patients (n=42)
were enrolled in the 5.4mg/kg arm.
The primary endpoint in DESTINY-CRC02 is confirmed ORR as assessed
by blinded independent central review. Secondary endpoints include
DOR, DCR, investigator-assessed confirmed ORR, clinical benefit
ratio, PFS, OS and safety. Results from DESTINY-CRC02 were
published in The
Lancet Oncology.11
DESTINY-CRC02 enrolled 122 adult patients (including 64 patients
with IHC 3+ receiving 5.4mg/kg) at multiple sites in Asia, Europe,
North America and Oceania. 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 China and the US as a neoadjuvant
treatment for adult patients with HER2-positive (IHC 3+ or
ISH+) Stage II or Stage 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, Saudi Arabia, Israel, Brazil and India as a
1st-line treatment for adult patients with unresectable or
metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as
determined by an FDA-approved test, 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 approved 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 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/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 40 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/or have no satisfactory alternative
treatment options based on efficacy results from
the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. 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 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
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References
1. Iqbal N, Iqbal N. Human
Epidermal Growth Factor Receptor 2 (HER2) in Cancers:
Overexpression and Therapeutic
Implications. Mol
Biol Int.
2014;2014:852748.
2. Cheng X. A comprehensive review of
HER2 in cancer biology and therapeutics. Genes (Basel). 2024;15(7):903.
3. Ismail A, et al. HER2
alterations across solid tumour: implications for comprehensive
testing. Oncologist. 2025;30(9):258.
4. Benli Y, et al.
HER2-targeted therapy in colorectal cancer: a comprehensive
review. Clin
Transl Oncol.
2025;27(9):3607-3624.
5. Uy NF, et al. HER2 in
non-small cell lung cancer: a review of emerging
therapies. Cancers (Basel).
2022;14(17):4155.
6. Haigh JE, et al. The
clinical utilisation and duration of treatment with HER2-directed
therapies in HER2-positive recurrent or metastatic salivary gland
cancers. Curr
Oncol. 2024;31(9):5652-5661.
7. Omar N, et al. HER2: An
emerging biomarker in non-breast and non-gastric
cancers. Pathogenesis.
2015;2(3):1-9.
8. Meric-Bernstam F, et
al. Efficacy and Safety of
Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid
Tumour: Primary Results From the DESTINY-PanTumor02 Phase II
Trial. J
Clin Oncol.
2023;42(1):47-58.
9. Li B, et al. Trastuzumab Deruxtecan
in HER2-Mutant Non-Small-Cell Lung Cancer. N
Engl J Med. 2022;386:241-251.
10. Smit E, et al. Trastuzumab deruxtecan in
patients with metastatic non-small-cell lung cancer
(DESTINY-Lung01): primary results of the HER2-overexpressing
cohorts from a single-arm, phase 2 trial. Lancet
Oncol.
2024;25(4):439-454.
11. Raghav K, et al. Trastuzumab deruxtecan
in patients with HER2-positive advanced colorectal cancer
(DESTINY-CRC02): primary results from a multicentre, randomised,
phase 2 trial. Lancet
Oncol.
2024;25(9):1147-1162.
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.
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AstraZeneca
PLC
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Date: 29 June 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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