a6521m
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 September 2023
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 recommended in EU for HER2-mutant NSCLC
15 September 2023
Enhertu recommended for
approval in the EU by CHMP for
patients with HER2-mutant advanced non-small cell lung
cancer
Recommendation based on DESTINY-Lung02 trial results which showed
AstraZeneca
and Daiichi Sankyo's Enhertu achieved
strong and durable tumour responses in previously treated
HER2-mutant disease
Enhertu
showed a confirmed objective response rate of 49% and median
duration of response of 16.8 months
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been
recommended for approval in the European Union (EU) as
monotherapy for the treatment of adult patients with advanced
non-small cell lung cancer (NSCLC) whose tumours have an activating
HER2 (ERBB2) mutation and who require systemic therapy following
platinum-based chemotherapy with or without
immunotherapy.
Enhertu is a specifically
engineered HER2-directed antibody drug conjugate (ADC) being
jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on the primary
results from the DESTINY-Lung02 Phase
II trial, which were presented at the IASLC 2023 World Conference
on Lung Cancer and simultaneously published in
the Journal
of Clinical Oncology.
In the trial, Enhertu (5.4mg/kg) demonstrated a
confirmed objective response rate (ORR) of 49.0% (95%
confidence interval [CI] 39.0-59.1) and a disease control rate
(DCR) of 93.1% (95% CI 86.4-97.2), as assessed by blinded
independent central review (BICR), in patients with previously
treated advanced or metastatic HER2-mutant (HER2m) NSCLC. One
(1.0%) complete response (CR) and 49 (48.0%) partial responses (PR)
were observed. The median duration of response (DoR) was 16.8
months (95% CI 6.4-not estimated [NE]). Median follow-up was 11.5
months at time of data cut-off of 23 December
2022.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "HER2-mutant non-small cell lung cancer is an
aggressive form of lung cancer that often affects younger patients
and has a poor prognosis, with limited approved
therapies. This milestone recognises the unmet need in the
European Union and if approved, Enhertu will provide the first targeted treatment
option for these patients."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said:
"Enhertu is the first therapy to demonstrate a strong
and durable tumour response in patients with previously treated
HER2-mutant advanced non-small cell lung cancer, validating HER2 as
an actionable target in lung cancer and supporting the potential to
provide a much-needed option for these patients. This CHMP opinion
is a positive step forward in advancing this HER2-directed antibody
drug conjugate for these patients and we look forward to the
European Commission decision."
The safety profile of Enhertu in the DESTINY-Lung02 trial was consistent
with previous clinical trials with no new safety signals
identified.
Notes
HER2m NSCLC
Lung cancer is the second most common form of cancer globally with
more than two million cases diagnosed in 2020.1 In
Europe, lung cancer is the third most commonly diagnosed cancer
with more than 477,000 cases diagnosed in 2020.2 Lung
cancer is also the leading cause of cancer-related deaths in
Europe, with nearly 400,000 deaths reported in
2020.2 Prognosis
is particularly poor for patients with metastatic NSCLC as only
approximately 9% will live beyond five years after
diagnosis.3
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including lung,
breast, gastric and colorectal cancers. Certain HER2 (ERBB2) gene
alterations (called HER2 mutations) have been identified in
patients with non-squamous NSCLC as a distinct molecular target,
and occur in approximately 2-4% of patients with this type of lung
cancer.4,5 While
HER2 gene mutations can occur in a range of patients, they are more
commonly found in patients with NSCLC who are younger, female and
have never smoked.6 HER2
gene mutations have been independently associated with cancer cell
growth and poor prognosis, with an increased incidence of brain
metastases.7 Next-generation
sequencing has been utilised in the identification of HER2 (ERBB2)
mutations.8,9
Although the role of anti-HER2 treatment is well established in
breast and gastric cancers, there were no approved HER2-directed
therapies in NSCLC prior to the approvals
of Enhertu by
the Israel Ministry of Health (MOH) Pharmaceutical Division, the
Japan Ministry of Health, Labour and Welfare and the accelerated US
Food and Drug Administration (FDA) approval
of Enhertu in
unresectable or metastatic HER2m NSCLC.10,11
DESTINY-Lung02
DESTINY-Lung02 is a global, randomised Phase II trial evaluating
the safety and efficacy of Enhertu in patients with HER2m advanced or
metastatic NSCLC with disease recurrence or progression during or
after at least one regimen of prior anticancer therapy that must
have contained a platinum-based chemotherapy. Patients were
randomised 2:1 to receive Enhertu 5.4mg/kg (n=102) or Enhertu 6.4mg/kg (n=50).
The primary endpoint of the trial is confirmed ORR as assessed by
BICR. Secondary endpoints include confirmed DCR, DoR and PFS
assessed by investigator and BICR, OS and
safety.
DESTINY-Lung02 enrolled 152 patients at multiple sites, including
Asia, Europe and North 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 topoisomerase I inhibitor payload,
an exatecan derivative,
via a stable tetrapeptide-based cleavable
linker.
Enhertu (5.4mg/kg)
is approved in more than 50 countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received a (or one or more) 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 40 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 Israel,
Japan and under accelerated approval in the US 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 trial. Continued approval for this
indication in the US may be contingent upon verification and
description of clinical benefit in a confirmatory
trial.
Enhertu (6.4mg/kg)
is approved in more than 30 countries for the treatment of adult
patients with locally advanced or metastatic HER2-positive gastric
or gastroesophageal junction (GEJ) adenocarcinoma who have received
a prior trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 and/or DESTINY-Gastric02
trials.
Enhertu development
programme
A comprehensive clinical development programme is underway
globally, evaluating the efficacy and safety
of Enhertu monotherapy across multiple HER2-targetable
cancers. Trials in combination with other anticancer treatments,
such as immunotherapy, are also underway.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi
Sankyo] and AstraZeneca entered into a global collaboration to
jointly develop and commercialise Enhertu (a HER2-directed ADC) in March
2019, and datopotamab
deruxtecan (a TROP2-directed ADC) in July
2020, except in Japan where
Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is
responsible for the manufacturing and supply
of Enhertu and datopotamab
deruxtecan.
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 (osimertinib)
and Iressa (gefitinib); Imfinzi (durvalumab)
and Imjudo (tremelimumab); Enhertu and
datopotamab deruxtecan in collaboration with Daiichi
Sankyo; Orpathys (savolitinib)
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/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 operates in
over 100 countries and its innovative medicines are 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)
WHO. International Agency of
Cancer Research. Cancer Today. 2020. Available
at: https://gco.iarc.fr/today/home.
Accessed September 2023.
2)
WHO. International Agency of
Cancer Research. Europe. 2020. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf.
Accessed September 2023.
3)
American Cancer Society. Lung
Cancer Survival Rates. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html.
Accessed September 2023.
4)
Liu
S, et al. Targeting HER2 Aberrations in Non-Small Cell Lung Cancer
with Osimertinib. Clin Cancer Res.
2018;24(11):2594-2604.
5)
Riudavets M, et al. Targeting HER2 in
non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated
review on therapeutic strategies in NSCLC harbouring HER2
alterations. ESMO Open. 2021;6(5):100260.
6)
Pillai RN, et al. HER2 mutations in lung
adenocarcinomas: A report from the Lung Cancer Mutation
Consortium. Cancer. 2017;123:4099-105.
7)
Offin M, et al. Frequency and Outcomes of Brain
Metastases in Patients With HER2-Mutant Lung
Cancers. Cancer. 2019;125(24):4380-4387.
8)
Hechtman, J, et al. The Past, Present, and Future
of HER2 (ERBB2) in Cancer: Approaches to Molecular Testing and an
Evolving Role in Targeted Therapy. Cancer
Cytopathol. 2019;
127(7):428-431.
9)
Gulilat, M, et al. Targeted next
generation sequencing as a tool for precision
medicine. BMC
Med Genomics. 2019;12(1):81.
10)
Zhou J, et al. Efficacy of PD-1/PD-L1 blockade
monotherapy in clinical trials. Ther Adv Med
Oncol. 2020;12:1758835920937612.
11)
Ren S, et al. Corrigendum to 'Consensus for HER2
Alterations Testing in Non-small Cell Lung
Cancer'. ESMO Open. 2022;7(3):100482.
Adrian Kemp
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:
15 September 2023
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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