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
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 approved in US for HER2-mutant NSCLC
12 August 2022 07:00 BST
Enhertu approved
in the US as the first HER2-directed therapy for patients with
previously treated HER2-mutant metastatic non-small cell lung
cancer
Based on DESTINY-Lung02 results which showed AstraZeneca and
Daiichi Sankyo's Enhertu reported a confirmed objective response
rate of 57.7% in patients with HER2-mutant disease
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved
in the US 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 Food and
Drug Administration (FDA)-approved test, and who have received
a prior systemic therapy.
This indication is approved under accelerated approval based on
objective response rate (ORR) and duration of response (DoR).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
Enhertu is a specifically
engineered HER2-directed antibody drug conjugate (ADC) being
jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.
The accelerated approval by the FDA was based on the results from
the DESTINY-Lung02 Phase II trial. An interim efficacy analysis in
a pre-specified patient cohort showed Enhertu (5.4mg/kg) demonstrated a confirmed ORR of
57.7% (n=52; 95% confidence interval [CI] 43.2-71.3), as assessed
by blinded independent central review (BICR), in patients with
previously treated unresectable or metastatic non-squamous
HER2-mutant (HER2m) NSCLC. Complete responses (CR) were seen in
1.9% of patients and partial responses (PR) in 55.8% of patients
with a median DoR of 8.7 months (95% CI 7.1-NE). Results from the
DESTINY-Lung02 trial will be presented at an upcoming medical
meeting.
Bob T. Li, MD, PhD, MPH, Medical Oncologist and
Physician-Scientist, Memorial Sloan Kettering Cancer Center, US,
said: "The approval of trastuzumab deruxtecan in non-small cell
lung cancer is an important milestone for patients and the oncology
community. After two decades of research into the role of targeting
HER2 in lung cancer, the approval of the
first HER2-directed treatment option validates HER2 as an
actionable target in lung cancer and marks an important step
forward for treating this patient population with unmet medical
needs."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "HER2-mutant non-small cell lung cancer is an
aggressive form of disease which commonly affects young patients
who have faced limited treatment options and a poor prognosis to
date. Today's news provides these patients with the opportunity to
benefit from a targeted therapy and highlights the importance of
testing for predictive markers, including HER2 in lung cancer, at
the time of diagnosis to ensure patients receive the most
appropriate treatment for their specific disease."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, Inc, said: "We are excited that the FDA has
granted accelerated approval for Enhertu for patients with HER2-mutant metastatic
non-small cell lung cancer. Enhertu has now been approved in three different
tumour types, underscoring its significant potential across several
HER2-targetable tumours. We are continuing to evaluate the efficacy
and safety of Enhertu versus standard chemotherapy in our DESTINY
clinical trials in lung cancer."
The safety of Enhertu was evaluated in an analysis of 101 patients
with unresectable or metastatic HER2m NSCLC who received at least
one dose of Enhertu (5.4mg/kg) in the DESTINY-Lung02 trial. In
the analysis, the safety profile of Enhertu was consistent with previous clinical trials
with no new safety concerns identified.
Concurrently with this approval, the FDA also approved companion
diagnostic tests to detect HER2 mutations in lung tumour tissue and
plasma. This is the third tumour type approved by the FDA
for Enhertu in three years, following approval in breast
and gastric cancers. The approval follows the recently
received Priority
Review in the US as well
as the Breakthrough Therapy
Designation granted in
2020 by the FDA for this specific type of lung cancer based on the
results of the DESTINY-Lung01 trial.
Notes
Financial considerations
Following US approval, an amount of $125m is due from AstraZeneca
to Daiichi Sankyo as a milestone payment for the HER2-mutant
metastatic NSCLC indication. The milestone will be capitalised as
an addition to the upfront payment made by AstraZeneca to Daiichi
Sankyo in 2019 and subsequent capitalised milestones, and will be
amortised through the profit and loss statement.
Sales of Enhertu in the US are recognised by Daiichi Sankyo.
AstraZeneca reports its share of gross profit margin
from Enhertu sales in the US as collaboration revenue in
the Company's financial statements.
Further details on the financial arrangements were set out in
the March 2019
announcement of the
collaboration.
HER2m NSCLC
Lung cancer is the second most common form of cancer globally, with
more than two million patients diagnosed in
2020.1 In
the US, lung cancer is the second most commonly diagnosed cancer,
with more than 236,000 patients expected to be diagnosed in
2022.2 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
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 Next-generation
sequencing is used to identify HER2 (ERBB2)
mutations.6
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, there were no approved HER2-directed therapies in
NSCLC prior to the accelerated approval of Enhertu in unresectable or metastatic
NSCLC.8,9
DESTINY-Lung02
DESTINY-Lung02 is a global Phase II trial evaluating the safety and
efficacy of two doses (5.4mg/kg or 6.4mg/kg)
of Enhertu in patients with HER2m 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.
The primary endpoint of the trial is ORR as assessed by BICR.
Secondary endpoints include disease control rate (DCR), DoR,
progression-free survival (PFS), investigator-assessed ORR, overall
survival (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.
DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial
evaluating the safety and efficacy of Enhertu in patients with HER2m (6.4mg/kg) or
HER2-overexpressing (defined as IHC 3+ or IHC 2+) [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 independent central review (ICR). Key
secondary endpoints include DoR, DCR, PFS, OS and safety.
DESTINY-Lung01 enrolled 181 patients at multiple sites, including
Asia, Europe and North America.
Data from the DESTINY-Lung01 Phase II trial was published
in The
New England Journal of Medicine.10 Primary
results from previously-treated patients with HER2-mutations
(cohort 2) of DESTINY-Lung01 demonstrated an ORR of 54.9% (95% CI
44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by ICR. One (1.1%) CR
and 49 (53.8%) PRs were observed. A confirmed 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 DoR
for Enhertu was 9.3 months. The median PFS was 8.2
months and the median 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.
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 30 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 several 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 (5.4mg/kg) is
approved in the US 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 chemotherapy 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 the US for the treatment of adult patients with
unresectable or metastatic NSCLC whose tumours have activating HER2
(ERBB2) mutations, as detected by an FDA-approved test, and who
have received a prior systemic therapy based on the results from
the DESTINY-Lung02 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 in breast and gastric cancer are currently
under review in several countries based on the DESTINY-Breast01,
DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and
DESTINY-Gastric02 trials, respectively.
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
tremelimumab; Enhertu (trastuzumab deruxtecan) 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.
WHO.
International Agency of Cancer Research. Cancer Today. 2020.
Available at: https://gco.iarc.fr/today/home. Accessed August
2022.
2.
American
Cancer Society. Key Statistics for Lung Cancer. Available at:
https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.
Accessed August 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 August 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.
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.
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.
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.
10.
Li
B T, et al. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell
Lung Cancer. NEJM. 2022; 386:241-251.
Dr. Li has provided uncompensated advisory services to AstraZeneca
and Daiichi Sankyo.
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:
12 August
2022
|
|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
|
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Title:
Company Secretary
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