a5058i
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 April 2022
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 granted Priority Review for HER2m
NSCLC
19 April 2022 07:00 BST
Enhertu granted
Priority Review in the US for patients with previously treated
HER2-mutant metastatic non-small cell lung
cancer
Based on pivotal DESTINY-Lung01 results showing AstraZeneca and
Daiichi Sankyo's Enhertu demonstrated a 54.9% tumour response
rate
If approved, Enhertu to provide patients with a much-needed
targeted therapy option
AstraZeneca and Daiichi Sankyo have received notification
of acceptance of the supplemental Biologics License Application
(sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment
of adult patients in the US with unresectable or metastatic
non-small cell lung cancer (NSCLC) whose tumours have a HER2
(ERBB2) mutation and who have received a prior systemic therapy.
The application has also been granted Priority
Review.
Enhertu is a
HER2-directed antibody drug conjugate (ADC) being
jointly developed by AstraZeneca and Daiichi
Sankyo.
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that, if approved, would offer
significant improvements over available options by demonstrating
safety or efficacy improvements, preventing serious conditions, or
enhancing patient compliance.1 The
Prescription Drug User Fee Act (PDUFA) date, the FDA action date
for their regulatory decision, is during the third quarter of 2022.
The Priority Review follows Breakthrough Therapy
Designation granted by the
FDA for Enhertu in this cancer type in May
2020.
Lung cancer is the second most common form of cancer globally, with
more than two million new cases diagnosed in
2020.2 For
patients with metastatic NSCLC, prognosis is particularly poor, as
only approximately 8% will live beyond five years after
diagnosis.3 There
are currently no HER2-directed therapies approved specifically for
the treatment of HER2-mutant NSCLC,4 which
occurs in approximately 2-4% of patients with non-squamous
NSCLC.4,5
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The DESTINY-Lung01 trial confirmed the
HER2 mutation as an actionable biomarker in non-small
cell lung cancer. If approved, Enhertu has the potential to become a new standard
treatment in this patient population, offering a much-needed option
for patients with HER2-mutant metastatic non-small cell lung cancer
who currently have no targeted treatment
options."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The
results of DESTINY-Lung01 showed that Enhertu is the first HER2-directed therapy to
demonstrate a strong and robust tumour response in more than half
of patients with previously treated HER2-mutant metastatic
non-small cell lung cancer. Seeking approval in the US for a third
tumour type in three years further demonstrates the significant
potential of Enhertu in treating multiple HER2-targetable
cancers."
The sBLA is based on data from the registrational DESTINY-Lung01
Phase II trial published in The
New England Journal of Medicine, and is supported by the Phase I trial
(DS8201-A-J101) published in Cancer
Discovery.
Primary results from previously-treated patients with
HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated a
confirmed objective response rate (ORR) of
54.9% (95% confidence interval [CI]: 44.2-65.4) in
patients treated with Enhertu (6.4mg/kg) as assessed by independent
central review (ICR). One (1.1%) complete response (CR) and 49
(53.8%) partial responses (PR) were observed.
A confirmed disease control rate (DCR) of 92.3% was seen with a
reduction in tumour size observed in most patients. After a median
follow-up of 13.1 months, the median duration of response (DoR)
for Enhertu was 9.3 months. The median progression-free
survival (PFS) was 8.2 months and the median overall survival (OS)
was 17.8 months.
The safety profile of the most common adverse events
with Enhertu in DESTINY-Lung01 was consistent with
previous clinical trials with no new safety concerns
identified.
Enhertu is being further
assessed in a comprehensive clinical development programme
evaluating efficacy and safety across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal
cancers.
Notes
HER2-mutant NSCLC
Lung cancer is the second most common form of cancer globally, with
more than two million new cases diagnosed in
2020.2 In
the US, lung cancer is the second most commonly diagnosed cancer,
with more than 236,000 new cases expected in
2022.6 For
patients with metastatic NSCLC, prognosis is particularly poor, as
only approximately 8% 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 gene
alterations (called 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.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.7 HER2
gene mutations have been independently associated with cancer cell
growth and poor prognosis, with an increased incidence of brain
metastases.8 Although
the role of anti-HER2 treatment is well established in breast and
gastric cancers, HER2 is an emerging biomarker in NSCLC with no
approved HER2-directed therapies.4,9 Next
generation sequencing has been utilised in the identification of
HER2 (ERBB2) mutations.10
DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial
evaluating the safety and efficacy of Enhertu in patients with HER2-mutant (6.4mg/kg) or
HER2-overexpressing (defined as IHC3+ or IHC2+) [6.4mg/kg and
5.4mg/kg] unresectable and/or metastatic non-squamous NSCLC who had
progressed after one or more systemic therapies. The primary
endpoint is confirmed ORR by ICR. Key secondary endpoints include
DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled approximately
180 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 40 countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received two or more prior anti-HER2-based regimens
based on the results from the DESTINY-Breast01
trial.
Enhertu (6.4mg/kg) is
approved in several 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 trial.
Enhertu development
programme
A comprehensive development programme is underway globally,
evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers.
Trials in combination with other anticancer treatments, such as
immunotherapy, are also underway.
Regulatory applications for Enhertu are currently under review in Europe, Japan,
the US and several other countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based regimen based on
the results from the DESTINY-Breast03 trial.
Enhertu also is currently
under review in Europe for the treatment of adult patients with
locally advanced or metastatic HER2-positive gastric or GEJ
adenocarcinoma who have received a prior anti-HER2-based regimen
based on the DESTINY-Gastric01 and DESTINY-Gastric02
trials.
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 (DS-1062; 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
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 Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed April 2022.
2. WHO. International Agency of Cancer Research. Cancer Today.
2020. Available at: https://gco.iarc.fr/today/home. Accessed April
2022.
3. American Cancer Society. Lung cancer survival rates. Available
at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html
.. Accessed April 2022.
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. Campbell, JD, et al. Distinct patterns of somatic genome
alterations in lung adenocarcinomas and squamous cell carcinomas.
Nature Genetics. 2016;48(6):607-16.
6. American Cancer Society. Key Statistics for Lung Cancer.
Available at:
https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.
Accessed April 2022.
7. Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A
report from the Lung Cancer Mutation
Consortium. Cancer. 2017;123:4099-105.
8. Offin M, et al. Frequency and Outcomes of Brain Metastases in
Patients With HER2-Mutant Lung Cancers. Cancer. 2019;125:4380-7.
9. Zhou J, et al. Clinical outcomes of patients with HER2-mutant
advanced lung cancer: chemotherapies versus HER2-directed
therapies. Ther Adv Med
Oncol.
2020;12:1-9.
10. 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 Cyto 2019; 127 (7): 428-431.
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:
19 April 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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